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Developing a Histology-Based Artificial Intelligence Biomarker to Predict Adjuvant Chemotherapy Benefit in Pancreatic Cancer

PURPOSE The choice of adjuvant chemotherapy in pancreatic ductal adenocarcinoma (PDAC) is mainly guided by patients' general condition. We hypothesized that tumor morphology may predict differential treatment benefit and tested whether deep learning applied to histology images could derive a biomarker of relative benefit from gemcitabine (GEM) versus modified FOLFIRINOX (mFOLFIRINOX) in resected PDAC. PATIENTS AND METHODS Standard whole-slide images from a retrospective multicentric series of 231 patients who underwent curative-intent pancreatectomy and received adjuvant mFOLFIRINOX (n = 54) or GEM (n = 177) were used to train regimen-specific histology models on disease-free survival (DFS), which were then combined into PANCprAId, a biomarker estimating personalized relative benefit from adjuvant GEM versus mFOLFIRINOX. External validation was performed in the randomized PRODIGE-24/CCTG PA6 trial (n = 313). RESULTS In PRODIGE-24/CCTG PA6, the treatment-specific histology scores used to construct PANCprAId stratified outcomes among patients treated with GEM (hazard ratio [HR], 1.69 [95% CI, 1.04 to 2.73]; P = .03) and mFOLFIRINOX (HR, 2.02 [95% CI, 1.4 to 3.0]; P < .001). When combined into PANCprAId, the biomarker identified subgroups with differential relative benefit from adjuvant GEM versus mFOLFIRINOX, with significant treatment interactions for DFS (interaction P = .003) and cancer-specific survival (interaction P = .001). Predicted sensitivity to each regimen was associated with distinct epithelial and stromal features. CONCLUSION Histology-based deep learning can derive a predictive biomarker of relative benefit from adjuvant GEM versus mFOLFIRINOX in resected PDAC.

Inside Back Cover: Nature‐Inspired Organic–Inorganic Hybridization Enables High‐Temperature and Multicolor Organic Phosphorescence (Angew. Chem. Int. Ed. 31/2026)

Enhancing Efficiency and Stability of Perovskite Solar Cells Through Electron‐Rich Covalent Organic Frameworks Radicals

ABSTRACT Effective regulation of perovskite crystallization is crucial for achieving high‐performance perovskite solar cells (PSCs). However, perovskite films typically exhibit low crystallinity and are plagued by abundant bulk and grain boundary defects. Simultaneously controlling crystallization kinetics, defect passivation, and energy level alignment remains a significant challenge. In this study, we designed and synthesized an electron‐rich covalent organic framework (COF FAT ) and further introduced N‐cationic radicals (COF Rad ) within its framework and pores via a one‐step post‐treatment. The introduction of these radicals significantly reduced the COFs bandgap, enhanced charge transfer, and minimized open‐circuit voltage (V OC ) loss. The ordered COFs structure, featuring multiple coordination sites (Ph–N and N• + ), modulated the crystallization process and effectively passivated bulk and grain boundary defects, thereby improving the crystallinity of α ‐perovskite. As a result, PSCs incorporating COF Rad achieved a remarkable power conversion efficiency (PCE) of 26.33% (certified 25.98%). These devices retained 88% of their initial PCE after 1000 h of thermal aging at 85°C, demonstrating outstanding durability. Moreover, COFs‐based PSCs exhibited excellent stability under continuous illumination and humid conditions. This work delivers the highest efficiency reported for COFs‐based PSCs to date and offers a new strategy for developing high‐performance and stable optoelectronic devices.

SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1–High, Locally Advanced, Unresectable or Metastatic Non–Small Cell Lung Cancer

PURPOSE Tiragolumab plus atezolizumab has shown encouraging survival outcomes in metastatic non–small cell lung cancer (NSCLC), primarily in patients with PD-L1–high tumors. We further evaluated the combination of tiragolumab plus atezolizumab in the phase III SKYSCRAPER-01 study. METHODS Patients with untreated, locally advanced unresectable/metastatic PD-L1–high (by central laboratory testing) NSCLC were randomly assigned 1:1 to receive either tiragolumab (600 mg) plus atezolizumab (1,200 mg) or placebo plus atezolizumab (1,200 mg) intravenously in 21-day cycles until disease progression, loss of clinical benefit, or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (INV-PFS) and overall survival (OS) in the primary analysis set (PD-L1–high per 22C3 assay). RESULTS Five hundred twenty-one patients were randomly assigned to either the tiragolumab plus atezolizumab group (n = 262) or the placebo plus atezolizumab group (n = 259). At the primary PFS analysis (Mar 12, 2022; median follow-up 9.9 months [IQR, 6.2-13.8]), median INV-PFS was 7.0 months (95% CI, 5.6 to 9.8) with tiragolumab plus atezolizumab and 5.6 months (95% CI, 4.4 to 7.0) with placebo plus atezolizumab (hazard ratio [HR], 0.78 [95% CI, 0.63 to 0.97]; P = .02 [nonsignificant]). At the final OS analysis (Sept 24, 2024; median follow-up 17.9 months [IQR, 6.7-39.0]), median OS was 23.1 months (95% CI, 17.7 to 28.8) with tiragolumab plus atezolizumab and 16.9 months (95% CI, 14.6 to 21.3) with placebo plus atezolizumab (HR, 0.87 [95% CI, 0.7 to 1.1]; P = .22 [nonsignificant]). Overall, 41.2% (n = 110/267) and 33.8% (n = 89/263) of patients experienced grade 3-4 adverse events with tiragolumab plus atezolizumab and placebo plus atezolizumab, respectively. Four and two treatment-related deaths occurred in each group, respectively. CONCLUSION Tiragolumab plus atezolizumab did not demonstrate a statistically significant INV-PFS or OS benefit over atezolizumab in patients with previously untreated PD-L1–high NSCLC.

Manganese Pyrophosphate Mineralized DNA Nanovaccine Elicits Potent Humoral and Cellular Immunity

ABSTRACT Subunit vaccines offer safety and precision but require adjuvants to overcome weak immunogenicity, particularly for the induction of cellular immunity. Herein, we develop a manganese pyrophosphate mineralized DNA bi‐adjuvant‐based subunit vaccine platform via biomineralization, which demonstrated the capability to elicit robust antigen‐specific cellular immune responses. The Mn/CpG bi‐adjuvant modulated the balance between Th1 and Th2 immune responses. More importantly, the synergistic activation of Toll‐like receptor 9‐like (TLR9) signaling pathways by CpG and cGAS‐STING pathways mediated by Mn(II) ions robustly enhanced cellular immunity, which was a magnitude of enhancement over commercial aluminum‐based adjuvants both in vitro and in vivo. Furthermore, the mechanistic studies revealed that the Mn(II)‐based nanoadjuvant effectively promoted Th1‐biased cellular immune response, as evidenced by an elevated IgG2a/IgG1 ratio and enhanced Th1‐associated cytokine secretion, alongside a potential reduction in regulatory T cell activity. These insights established critical design principles essential for the development of next‐generation manganese‐derived adjuvant systems, thereby advancing the frontiers of vaccinology and immunology.

Anti-TIGIT in PD-L1–High Advanced Non–Small Cell Lung Cancer: Insights From SKYSCRAPER-01 and the Path Forward

Ferritin Iron Mineralisation: Route of Fe ³⁺ Transfer From the Ferroxidase Centre to the Inner Cavity of Human H‐Chain Ferritin

ABSTRACT Ferritin‐catalysed Fe 2+ oxidation by reaction with O 2 occurs at an intra‐subunit diiron site known as the ferroxidase centre (FoC). Currently, how Fe 3+ , the key substrate for iron core nucleation/mineralisation, transfers from the FoC to the inner protein surface/central cavity where the mineral is laid down is unknown. Iron‐binding sites that become occupied following exposure of anaerobic, Fe 2+ ‐bound human cytosolic H‐chain ferritin (HuHF) to O 2 were identified by time‐resolved x‐ray crystallography. In addition to the two FoC iron sites, three further sites were identified, each involving Glu61 as a coordinating residue. Substitution by a non‐coordinating residue (variant E61A) eliminated binding at these additional iron sites. Solution kinetic studies of Fe 2+ oxidation and iron core mineralisation in wild‐type HuHF and its E61A variant showed that rapid Fe 2+ oxidation was unaffected by loss of Glu61, ruling out an important role for these sites in either guiding Fe 2+ to the FoC, or in the mechanism of FoC‐catalysed Fe 2+ oxidation. Conversely, the transfer of Fe 3+ out of the FoC and core mineralisation were both severely affected in the E61A variant. A mechanism for Fe 3+ transfer from the FoC to the inner protein surface is proposed.

Time-Varying Effects of Copy Number Alteration Clustering: Methodologic Concerns in Survival Analysis of Relapsed/Refractory Germ Cell Tumors

Development of Sub‐50 nm Core–Shell Silica Nanoparticles With Controlled In Vivo Behavior for ¹⁹ F Magnetic Resonance Imaging

ABSTRACT 19 F magnetic resonance imaging ( 19 F MRI) enables quantitative and background‐free detection, but its inherently low sensitivity demands probes with high fluorine density and favorable pharmacokinetics. Perfluorocarbon (PFC)‐encapsulated nanoparticles are a promising class of 19 F MRI probes that demonstrate high 19 F MR sensitivity. However, their relatively large size (usually over 70 nm) results in slow hepatic clearance and limited tumor accumulation. Herein, we developed sub‐50 nm perfluoro‐15‐crown‐5‐ether (PFCE)‐loaded core–shell silica nanoparticles (s‐FLAME), which combine high 19 F signal intensity with reduced size distribution. The established one‐pot double‐emulsion‐based synthesis shortened the silica shell formation time, suppressed droplet coalescence, and kinetically fixed PFCE emulsions at smaller sizes, resulting in the preparation of uniform core–shell nanoparticles (s‐FLAME‐OH) with a core diameter of 30 nm—significantly smaller than previously reported liquid‐core systems. A co‐condensation approach yielded carboxyl‐functionalized nanoparticles (s‐FLAME‐COOH), which reduced cytotoxicity and improved colloidal stability. The resulting nanoparticles exhibited strong, concentration‐dependent 19 F MRI signals. In vivo 19 F MRI revealed accelerated hepatic clearance and tumor‐associated signals, indicating size‐dependent biodistribution. This study establishes a versatile strategy for tuning the size and surface chemistry of silica‐based 19 F MRI nanoprobes to achieve controlled in vivo behaviors, providing a promising platform for future molecular imaging applications.

Five-Year Outcomes of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy for Locally Advanced Rectal Cancer: Updated Results of the STELLAR Trial

This updated analysis of the STELLAR trial reports 5-year outcomes comparing short-course radiotherapy followed by chemotherapy (SCRT-based total neoadjuvant therapy [TNT]) with standard long-course chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Patients with distal or middle-third LARC were randomly assigned to receive either SCRT-based TNT or CRT. At a median follow-up of 68.7 months, the 5-year disease-free survival (DFS) was 62.0% in the TNT group and 58.7% in the CRT group, with a hazard ratio (HR) for DFS of 0.849 (95% CI, 0.662 to 1.089). Five-year overall survival (OS) was significantly higher with TNT (78.1% v 69.7%; HR, 0.739 [95% CI, 0.550 to 0.993]). Distant metastasis (DM) and locoregional recurrence (LRR) rates were similar between the two groups. In high-risk patients (per European Society for Medical Oncology criteria), TNT was associated with improved OS (HR, 0.663 [95% CI, 0.469 to 0.937]) and showed a nonsignificant trend toward improved DFS (HR, 0.765 [95% CI, 0.568 to 1.032]). In patients with DM or LRR, TNT was associated with both improved postrecurrence progression-free survival (HR, 0.691 [95% CI, 0.497 to 0.961]) and postrecurrence survival (HR, 0.698 [95% CI, 0.490 to 0.994]). These results suggest that SCRT-based TNT provides a durable survival advantage and is a viable alternative to CRT, especially in patients with high-risk disease.

Molecular Conformation‐Locking for Eye Care and Highly Efficient Narrowband Deep‐Blue Organic Electroluminescence

ABSTRACT The advancement of high‐color‐purity displays demands deep‐blue emitters that fulfil stringent colorimetric standards while minimizing photobiological risks to eye health. We propose a skeletal rigidity strategy by fusing a five‐membered oxa‐heterocycle into a classical MR‐TADF skeleton ( ν ‐DABNA), which simultaneously introduces rigidity enhancement via aromatic fusion and conformational locking. This approach resulted in an increased optical bandgap and the formation of intramolecular C–H···O secondary interactions, and thus a systematic blue‐shift and narrowing emission spectrum. In toluene solution, the proof‐of‐concept molecule, v ‐DABNA‐O, exhibits a narrowband deep‐blue emission peaking at 460.4 nm, with an ultra‐narrow full‐width at half maximum (FWHM) of 12.0/69.8 nm/meV. As a result, the ν ‐DABNA‐based device with a sensitizer achieves a maximum external quantum efficiency of 36.1%, a narrow electroluminescence spectrum with an FWHM of 17.9/95.4 nm/meV, and a Commission Internationale de l’Éclairage coordinate of (0.135, 0.091). Crucially, the device achieves a sharp suppression of high‐energy emission below 450 nm, directly addressing the imperative for visual safety. This work successfully addresses the trilemma in deep‐blue emitters by simultaneously achieving an ultra‐narrow emission bandwidth, a precisely positioned emission peak, and suppressed spectral intensity below 450 nm.

Dual‐Atom Dopants Activated Copper Dilute Alloy Boosts Electroreduction CO ₂ ‐to‐C ₂₊ Products at Ampere‐Level Current Density

ABSTRACT Electrochemical CO 2 reduction reaction (CO 2 RR) with H 2 O as the hydrogen donor provides a sustainable and green route to product energy‐dense multi‐carbon (C 2+ ) products, but guiding selectivity remains challenging due to competing pathways. Here, we construct atomic Al and Zn into nanoporous Cu to regulate the adsorption energies of *CO and *H intermediates. Efficient electrosynthesis of C 2+ products from CO 2 RR are achieved, delivering a Faradaic efficiency approaching 91.4%, a partial current density of −1.5 A cm −2 , and a C 2+ /C 1 ratio up to 26.9 in gas‐fed flow cells. Experimental and theoretical studies reveal that the Al 1 ─Cu sites preferentially promote CO 2 activation, while Zn 1 ─Cu sites facilitate H 2 O dissociation to ensure intermediate hydrogenation, thus synergistically driving the conversion of *CO to *CHO and promoting asymmetric *CHO─*CO coupling to form C 2+ products on Cu site. This work establishes a dual‐atom alloy that enhances proton supply to CO 2 and intermediates while regulating *CO coverage, providing a rational design concept for electrocatalysts toward the selective reduction of CO 2 to C 2+ products.

Single‐Atom Iron‐Catalyzed Oxidative Esterification: From Methylarenes to the Upcycling of Polystyrene and Lignin‐Derived Feedstocks

ABSTRACT The catalytic oxidation of C─H bonds represents a transformative strategy for converting abundant hydrocarbons into high‐value functional molecules. We report a sustainable heterogeneous methodology for the oxidative esterification of methyl (hetero)arenes and the oxidative C─C bond cleavage of alkyl arenes to synthesize aromatic methyl esters using molecular oxygen in water. This process is driven by an atomically dispersed iron catalyst supported on N‐doped porous carbon (Fe‐SAC), featuring well‐defined Fe‐N 4 active sites. The catalyst exhibits exceptional activity and selectivity, effectively overcoming the intrinsic inertness of C(sp 3 )─H and C─C bonds without the need for noble metals or hazardous additives. Mechanistic investigations, combining kinetic studies, in situ DRIFTS, and DFT simulations, identify superoxide radicals (O 2 ●− ) as key reactive species and pinpoint benzylic C─H bond cleavage as the rate‐determining step. Beyond small molecules, the Fe‐SAC system demonstrates high efficiency in the valorization of lignin derivatives and the chemical upcycling of polystyrene waste into value‐added esters. Its remarkable stability, ease of recycling, and use of an eco‐friendly solvent/oxidant system make this iron‐catalyzed process a cost‐effective and green alternative to traditional esterification methods.

γ‐Ray Regulated Host–Guest Molecular Recognition

ABSTRACT Decades of advances in light‐responsive host–guest supramolecular systems allow precise molecular switching and photoactivation, yet their in vivo use is severely limited by the weak tissue penetration of UV/visible light. Ionizing radiation such as γ‐rays possesses outstanding deep‐tissue penetration, which has been widely applied in clinical radiology and radiotherapy. Herein, we develop a γ‐irradiation‐regulated host–guest recognition system based on azobenzene derivatives and macrocyclic hosts (cyclodextrins and cucurbiturils). At a clinical dose of 2 Gy, γ‐radiation triggers cis‐to‐ trans isomerization of azobenzene and enables efficient molecular recognition with macrocycles. γ‐Rays outperform blue light in inducing isomerization even through centimeter‐thick porcine tissues, and the system exhibits excellent recyclability over ten irradiation cycles. Moreover, γ‐ray‐regulated ternary recognition realizes in situ hydrogelation, constructing double‐network hydrogels with simultaneous mechanical reinforcement, stiffening and self‐healing. The hydrogel achieves tensile strength of ∼23 MPa and toughness of ∼30 MJ m −3 , comparable to engineered elastomers while retaining supramolecular adaptability. This radiation‐regulated molecular recognition offers a universal platform for remotely programming soft material mechanics and holds great potential for in vivo applications.

Analysis of physical and physiological training demands in women’s basketball

Purpose The primary aim of the present study was to analyze the physical and physiological demands associated with different training tasks in women’s basketball. Methods Fourteen basketball players were continuously monitored for 22 weeks using WIMU PRO ® ™ local positioning system and GARMIN ® heart rate monitors. The variables examined included: distance (DIST in m), number of accelerations (>2 m·s -2 , HACC) and decelerations (<−2 m·s -2 , HDEC); high speed running (>18 km·h -1 , HSR in m), number of jumps (JUMPS), player load (PL in arbitrary units) and heart rate zones (>80% of maximum heart rate, HRZ in seconds). Training tasks were classified into three orientations: directed-oriented (DIR, drills without opposition), special-oriented (SPE, small-sided games), and competitive-oriented (COM, 4-on-4 and 5-on-5 formats); and further grouped by three levels of court space. The Shapiro–Wilk test was used to verify data normality. Linear mixed-effects models were used to analyze all variables. Skewed variables were log-transformed to meet model assumptions. Significance was set at p < 0.05. Results The SPE tasks showed higher values than COM tasks (p < 0.001) in all variables except for HRZ. Also, SPE tasks reported greater values than DIR in the following variables: HRZ and HSR (both p < 0.001) and PL (p = 0.008). Finally, DIR tasks showed higher values than COM tasks in DIST, HACC, HDEC and JUMPS (all p < 0.001), whereas COM tasks exhibited higher values than DIR tasks in HRZ (p < 0.001). Considering the court space in which the tasks were performed, differences were found in all the variables analyzed, with larger spaces generally resulting in greater demands in most variables. Conclusions The results describe that task orientation and court space influence the load demands in women’s basketball. DIR and SPE tasks elicited greater intensities than COM tasks, suggesting that training design should be strategically adapted according to the desired physical and physiological stimuli.

Solar‐Driven Carbon–Nitrogen Coupling Between Biomass‐Derived Alcohol and Ammonia for High‐Value Amine Synthesis

ABSTRACT Photocatalytic carbon–nitrogen (C–N) coupling of biomass‐derived alcohols and inorganic nitrogen sources provides a sustainable route to high‐value amines but is often limited by inefficient C–H activation and uncontrollable nitrogen conversion kinetics. Herein, we report a synergistic redox pathway integrating anaerobic alcohol dehydrogenation and imine hydrogenation, enabled by an atomically dispersed Au species coordinated with three foreign phosphorus atoms on CdS nanorods (AuP 3 ‐CdS). In situ spectroscopy and theoretical calculations elucidate that Au–P 3 sites boost charge separation and enable both alcohol dehydrogenation and imine hydrogenation with optimal reaction energies compared to the conventional Au species coordinated with three intrinsic sulfur atoms on CdS nanorods (AuS 3 ‐CdS). These characteristics enable AuP 3 ‐CdS to achieve a furfurylamine production rate of 41.48 mmol g −1 h −1 with a selectivity of 99.1% from biomass‐derived furfuryl alcohol and ammonia, which is 63 times higher than that of conventional AuS 3 ‐CdS, and notably surpasses other P‐coordinated metal‐loaded CdS catalysts. Moreover, AuP 3 ‐CdS is also applicable to various other alcohols for diverse amine synthesis. Furthermore, this catalyst demonstrates a production rate of 14.24 mmol g −1  h −1 with a selectivity of 97.1% under concentrated natural sunlight (3773 mW cm −2 ) in a scalable reactor, providing a promising strategy for the photosynthetic synthesis of amines from diverse biomass‐derived alcohols and ammonia.

Artificial intelligence for early detection of diabetic retinopathy: A vision transformer-based approach

Background Early identification of diabetic retinopathy (DR), which is a primary cause of vision impairment globally, is a crucial phasis for effective intervention and treatment. Traditional screening workflows rely on manual diagnosis by ophthalmologists, which remains the gold standard but can be time-consuming and subject to variability due to human factors. To support and enhance the screening process, artificial intelligence (AI)-based tools have shown promise in automating DR detection, particularly with recent advances in deep learning. However, medical images with long-range dependencies and spatial linkages can be challenging for CNN-based algorithms to handle. Methods This paper proposes a Vision Transformer (ViT)-based model, specifically using a Compact Convolutional Transformer (CCT), for early automated detection of DR. The model uses self-attention techniques to improve feature extraction and classification performance; combining three main stages: the CCT tokenizer, transformer encoder, and sequence pooling. The proposed approach was trained on public datasets (EyePACS and APTOS 2019) and evaluated against state-of-the-art deep learning architectures. Results Our experimental findings demonstrate that ViT performs among the best in the current state of the art with an overall accuracy of 97% and F1-scores above 0.95 across all DR severity levels. Our system is primarily designed for the pre-screening stage of diabetic retinopathy workflows, enabling rapid and reliable identification of potential DR cases for further clinical evaluation. Conclusion These results highlight the potential of transformer-based designs in medical picture analysis, as well as the implications for telemedicine and e-health solutions in real-time, especially in cases of low-resource settings.

Gold(III) Semiquinone Complexes: Synthesis, Structure, and Application in Photocatalysis

ABSTRACT Recently, hemilabile ligands have been found to enable two‐electron Au(I)/Au(III) redox cycling. Yet, single‐electron processes and the use of redox‐active ligands in gold chemistry remain largely underexplored. Here, we report the synthesis, isolation, full characterization and first photocatalytic application of Au(III) semiquinone complexes. The latter are easily obtained via one‐electron oxidation of Au(III) catecholate precursors. Experimental and DFT studies establish that oxidation occurs at the O^O ligand while the gold center retains its +3 oxidation state. Owing to their square‐planar geometry and electron‐rich character, Au(III) catecholate complexes readily engage into electron donor–acceptor (EDA) interactions with organic substrates. Upon visible‐light irradiation, these EDA adducts undergo photoinduced single‐electron transfer, enabling the generation of aryl radicals from aryldiazonium salts. This reactivity translates into efficient photocatalytic C–H arylation of heterocycles under mild conditions, with broad substrate scope and high functional group tolerance. Variation of the redox‐active and ancillary ligands provides a simple means to tune the system, enabling catalytic optimization as substantiated with challenging electron‐rich aryldiazonium partners. Mechanistically distinct from established gold photoredox systems, this work delineates a new strategy for standalone Au(III)‐mediated photoredox catalysis and highlights the broader potential of redox‐active ligands in expanding the reactivity landscape of gold complexes.

Persistence of viable opportunistic pathogens in a multi-stage natural wastewater treatment system

Nature-based wastewater treatment systems are increasingly implemented to support water reuse in arid regions, yet their effectiveness in removing viable culturable opportunistic pathogens remains insufficiently characterized. In this exploratory, culture-based study, we assessed bacterial population dynamics across a five-stage natural wastewater treatment system (Wadi Hanifa, Riyadh, Saudi Arabia), tracking culturable bacteria from secondary-treated influent to sand-filtered effluent. Water samples were collected at five sequential treatment stages and analyzed for physicochemical parameters, total culturable bacterial abundance, bacterial diversity, taxonomic composition, and antimicrobial susceptibility of persistent isolates. Total culturable bacterial counts decreased by approximately 1.1 log 10 CFU mL ‒1 across the system, accompanied by an approximately 50% reduction in observed isolate richness. The fecal indicator Escherichia coli was detected only in upstream and intermediate stages (sampling locations L3.1-L3.3) and was absent from downstream samples. In contrast, the opportunistic pathogen Klebsiella pneumoniae was recovered across all five treatment stages and accounted for 44.4% (8/18) of all morphologically distinct isolates grown on the selected culture media. Turbidity declined by 71% along the treatment train and showed a strong positive correlation with bacterial richness (Kendall’s τ = 0.84, p = 0.038), although this exploratory correlation should be interpreted with caution given the small sample size (n = 5 stages). Phenotypic antimicrobial susceptibility testing revealed multidrug resistance (MDR) in 62.5% (5/8) of K. pneumoniae isolates, although all remained susceptible to amikacin and meropenem. Under the conditions examined, multi-stage natural wastewater treatment substantially reduced overall bacterial abundance and diversity but did not eliminate viable, multidrug-resistant Klebsiella pneumoniae . The discordance between fecal-indicator removal and opportunistic pathogen recovery highlights system-specific limitations of indicator-based monitoring for assessing microbial safety in wastewater reuse systems. Given the limited isolate number (n = 8 K. pneumoniae ) and the absence of molecular resistance-gene characterization, broader claims about wastewater as a dissemination pathway for antimicrobial resistance cannot be drawn from these data. These findings are based on a single cross-sectional sampling event and should be considered hypothesis-generating rather than confirmatory.

Bifurcation of *COOH Pathway Determines HCOOH Formation in CO ₂ Electroreduction on Bismuth

ABSTRACT Bismuth (Bi) is a promising electrocatalyst for the CO 2 reduction reaction (CO 2 RR) to formic acid (HCOOH), yet its mechanism remains a subject of debate. While the pathway involving the oxygen‐bound *OCHO intermediate is conventionally accepted, experimentally observed carbon‐bound species have been largely overlooked. In this work, we resolve this mechanistic ambiguity by combining constant‐potential ab initio molecular dynamics (AIMD) simulations with spectroscopic evidence. We reveal that the reaction on Bi is governed by the bifurcation of the *COOH pathway, which favors HCOOH formation over CO. We also identify an *H‐mediated pathway as an alternative route at low potentials where *CO 2 activation is suppressed. Supported by the experimental detection of *COOH, our findings suggest that this mechanism is likely a general feature across other metal surfaces, such as Ag, Cu, and In. Consequently, we bring the *COOH‐mediated mechanism to the forefront of HCOOH production, highlighting the need to consider this pathway in the rational design of future HCOOH‐selective electrocatalysts.