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Sustainable forest planning: Assessing biodiversity effects of Triad zoning based on empirical data and virtual landscapes

The Triad framework seeks to balance the economic and ecological functions in forested landscapes by combining intensively, extensively, and unmanaged areas, assuming a higher support to biodiversity in extensively rather than in intensively managed forests. We quantified the effects of Triad zoning on biodiversity in (sub)montane eutrophic European beech forests. Using a European-wide multitaxon database and a “virtual” landscape approach (i.e., by resampling empirical data), we evaluated how the proportion of Triad management categories affected the landscape-level species diversity of birds, saproxylic beetles, vascular plants, epiphytic bryophytes, lichens, and wood-inhabiting fungi, as well as multitaxonomic diversity. The results varied greatly among taxonomic groups. Multitaxonomic diversity peaked in landscapes composed of 60% unmanaged and 40% intensively managed forests. While intensive management can benefit some taxa through the creation of open habitats, unmanaged forests are the backbone of biodiversity conservation, underlining the need to safeguard the remaining old-growth forests under natural dynamics, and to extend the current area of unmanaged forests in Europe. Extensive forest management, however, did not contribute to biodiversity conservation as expected. As withdrawing such a high proportion of European forest landscapes from management is unfeasible given the increasing demand for timber, efforts are needed to increase the presence of structural features supporting biodiversity into extensively managed forests.

Citronellol silver nanoconjugates as a therapeutic strategy for glioblastoma through computational and experimental evaluation

Inorganic sulfate is critical for <i>Mycobacterium tuberculosis</i> lung tissue colonization and redox balance

Tuberculosis remains the deadliest infectious disease caused by a single pathogen, highlighting the urgent need for novel therapies. A deeper understanding of Mycobacterium tuberculosis metabolism could uncover specific vulnerabilities and inform the development of new treatments. Sulfur, essential for bacterial growth and survival, fuels key pathways including redox buffering and coenzyme production. Although previous studies suggest that M. tuberculosis utilizes various substrates to meet its sulfur requirements, the primary sources of sulfur exploited during in vivo infection remain unclear. Here, we reveal that M. tuberculosis acquires inorganic sulfate through the SubI-CysTWA transporter during macrophage infection. Using nanoSIMS (high spatial resolution Secondary Ion Mass Spectrometry) analysis, we observed significant sulfate-derived 33 S enrichment in intracellular bacteria, correlating with metabolic activity. Deletion of subI abolished sulfate uptake, impairing bacterial growth in vitro and reducing M. tuberculosis survival in murine macrophages and lungs of infected mice. Finally, our data demonstrate that sulfate acquisition is essential for maintaining mycobacterial redox balance and resisting nitrosative stress in vitro and in vivo. Thus, unlike many intracellular pathogens, M. tuberculosis depends on an energetically costly inorganic sulfate assimilation pathway to survive in the nutrient-limited host environment. These findings challenge prior assumptions that organic reduced sulfur sources, such as methionine, fuel M. tuberculosis sulfur metabolism during infection. Since animal cells lack a sulfate assimilation pathway, uncovering the critical role of SubI-CysTWA-mediated sulfate import in M. tuberculosis pathogenesis highlights this pathway as a promising pathogen-specific therapeutic target. Targeting this system could either directly impair M. tuberculosis survival during infection or sensitize bacilli to antibiotic-induced oxidative stress by disrupting redox homeostasis.

Path-based evaluation of deep learning models for solving inverse kinematics in a revolute-prismatic robot

Understanding the social benefits for playful employees in the workplace

De novo design of potent inhibitors of clostridial family toxins

Clostridioides difficile remains a leading cause of hospital-acquired infections, with its primary virulence factor, toxin B (TcdB), responsible for severe colitis and recurrent disease. The closely related toxin, TcsL, from Paeniclostridium sordellii , causes a rarer but often fatal toxic shock syndrome, particularly in gynecological and obstetric contexts. We report the de novo design of small protein minibinders that directly neutralize TcdB and TcsL by preventing their entry into host cells. Using deep learning and Rosetta-based approaches, we generated high-affinity minibinders that protect cells from intoxication with picomolar potency and, in the case of TcsL, prolonged survival following lethal toxin challenge in mice. The designed proteins against TcdB demonstrate exceptional stability in proteolytic and acidic environments, making them well-suited for oral delivery—a valuable feature for treating C. difficile infections localized to the gastrointestinal tract. For TcsL, potent inhibitors were identified from 48 initial designs and 48 optimized designs, highlighting the potential of computational design for rapidly developing countermeasures against life-threatening bacterial toxins.

Predicting biomass global warming potential with FT-NIR spectroscopy

A pH-responsive nanocarrier of peanut shell carbon quantum dots as a promising delivery of doxorubicin for cancer therapy

PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors

Immunotherapy modalities have revolutionized cancer treatment for a number of metastatic and treatment-refractory tumor types. Still, many malignancies that lack T cell infiltration and are termed immunologically “cold” fail to respond to these modalities. One approach to increase tumor immunogenicity has been to induce stimulator of interferon gene (STING) and downstream interferon signaling that is often dysregulated in cold tumors. Despite some early success of STING agonists in preclinical cancer models, these approaches have not been successful in the clinic due to poor tumor penetrance and systemic toxicities. Here, we performed a genome-wide CRISPR screen to uncover therapeutic targets to activate STING expression in human tumors. We identified the lysosomal hydrolase Palmitoyl Protein Thioesterase1 (PPT1) as a negative regulator of STING highly expressed in cold ovarian and prostate tumors. Genetic or pharmacological PPT1 suppression increased STING protein stability and its downstream activation of interferon and inflammatory cytokine signaling to enhance T cell migration. Treatment of preclinical prostate and ovarian cancer models expressing low levels of STING with the small molecule PPT1 inhibitor GNS561 enhanced STING expression and activation, leading to infiltration and activation of cytotoxic T cells that turned these tumors “hot” and reduced tumor growth, fibrosis, and dissemination without toxicity. Further analysis demonstrated that PPT1 is associated with reduced STING expression, CD8 + T cell numbers, overall survival, and immunotherapy outcomes in ovarian and prostate cancer patients. Thus, PPT1 inhibition may be a promising approach to activate STING and potentiate the effects of immunotherapy in cold tumors.

A stochastic evolutionary game of boosting urban low-carbon development in China

The discovery of adzuki bean ( <i>Vigna angularis</i> ) in eastern China during the 9th millennium BP and its domestication in East Asia

Adzuki bean ( Vigna angularis ) is a key legume widely cultivated in East Asia, prized for both its nutritional value and nitrogen-fixing properties. This paper presents one of the oldest directly dated archaeological finds of adzuki bean, recovered from the Xiaogao site in Shandong, China, and dated to 8985-8645 and 8032-7939 cal. BP—predating previously known Chinese records by at least 4,000 y (approximately 6,000 y considering published directly dated evidence alone). The evidence suggests that adzuki beans formed part of an Early Neolithic multicropping system alongside millet, rice, and soybean in a well-established agricultural tradition in the Lower Yellow River region. Morphometric analysis of adzuki beans from 41 archaeological sites across East Asia reveals a gradual increase in seed size over time when regional data are aggregated, yet highlights distinct regional trajectories. These patterns reflect complex, multiregional domestication processes shaped by both cultural practices and ecological conditions. Notably, the marked differences in bean sizes observed between the Neolithic Yellow River and Jomon-period Japan could be contingent on the distinctions in dietary regimes and associated selective pressures.

Nationwide analysis of renal outcomes in chronic hepatitis B patients treated with Tenofovir Alafenamide vs. Entecavir

VOC injection into a house reveals large surface reservoir sizes in an indoor environment

The total partitioning capacity of indoor surface reservoirs determines the mechanism by which humans receive nondietary exposure to organic contaminants, via inhalation, dermal uptake, and dust ingestion. And yet, this capacity is largely unknown. Surface organic films are ubiquitously present but have very low partitioning volume being only 10’s of nanometer thick, whereas other surface reservoirs such as building materials and furnishings can be permeable or porous with large surface areas at the molecular level. Here, we assess the total partitioning capacity of volatile organic compounds (VOCs) in an indoor environment from the measured kinetics of VOC surface uptake after injection of compounds with variable volatility into a well-characterized, unoccupied test house. We show that the size of the indoor surface reservoirs is very large with an octanol-equivalent average thickness on the order of micrometers, indicating that permeable/porous materials such as painted surfaces and wood are likely the major surface reservoirs in the house rather than organic surface films. Large surface reservoirs result in compounds with octanol-air partition coefficients ( K OA ) larger than 10 5 being predominantly partitioned to indoor surface reservoirs, making them hard to be removed via ventilation. This result significantly impacts our understanding of VOC fate and human exposure in indoor environments. With such a large partitioning capacity, organic contaminants will have much longer indoor residence times than previously predicted.

DNA metabarcoding analysis of stomach flushing contents reveals the exceptionally diverse diet of the golden alpine salamander

Triple checkpoint blockade of PD-1, Tim-3, and Lag-3 enhances adoptive T cell immunotherapy in a mouse model of ovarian cancer

The five-year survival rate for ovarian cancer patients remains below 50%, underscoring the need for innovative therapies. One promising approach involves engineering T cells to specifically target proteins uniquely overexpressed in tumors, thereby controlling tumor growth without toxicity to healthy tissues. Mesothelin (MSLN) contributes to the malignant and invasive phenotype in ovarian cancer and has limited expression in healthy cells, making it a candidate immunotherapy target. Our previous results in a mouse model of ovarian cancer demonstrated that T cells engineered to express a T cell receptor (TCR) targeting MSLN (TCR MSLN ) mediated therapeutic activity, delaying tumor growth and prolonging mouse survival. However, inhibitory ligands expressed in the tumor microenvironment (TME) interacted with inhibitory receptors on activated T cells, suppressing antitumor function. We hypothesized combining engineered T cells with checkpoint blockade would enhance T cell function and improve therapeutic efficacy, but administration of monospecific antibodies targeting individual inhibitory pathways had no significant impact on T cell efficacy. By contrast, the combination of PD-1, Tim-3, and Lag-3 blockade with engineered T cells significantly improved T cell function and overall animal survival relative to treatment with antibody alone or TCR MSLN with singlet or doublet antibody combinations. Single-cell RNA sequencing revealed TCR MSLN T cells treated with the triplet antibody combination increased expression of genes involved in interferon responses and metabolic function, and reduced expression of genes associated with exhaustion. These results suggest that strategies to disrupt multiple inhibitory pathways simultaneously may be necessary for improved adoptive T cell therapy efficacy in patients.

ImMLPro platform for accessible machine learning and statistical analysis in digital agriculture and beyond

Characterization of exoplanets in the James Webb Space Telescope era

Validation and reliability of mechanical stiffness assessment tools in multilayered polyurethane phantom models of healthy and diabetic plantar soft tissues

Abstract Plantar soft tissue stiffness plays a crucial role in the development of diabetic foot complications, but in vivo assessments are constrained by anatomical variability and probe-induced measurement artifacts. To develop anatomically layered polyurethane phantom models mimicking healthy and diabetic plantar soft tissues and evaluate the reliability and concurrent validity of four mechanical stiffness assessment tools, [MyotonPRO, Shore Durometer, IndentoPRO, and Tissue Compliance Meter (TCM)] against Shear Wave Elastography (SWE). Six regional phantom models (calcaneus, midfoot, forefoot) with skin, fat pad, fascia, and muscle layers were fabricated. SWE was performed in no-contact mode to eliminate surface compression, improving measurement consistency. A total of 162 configurations were tested under blinded and randomized conditions. Intra- and inter-rater reliability was assessed using ICCs; concurrent validity was evaluated via correlation and regression analyses with SWE. All devices demonstrated excellent reliability (ICC range: 0.88–0.99). SWE-derived stiffness was significantly higher in diabetic models, especially in the calcaneal and midfoot regions (p &lt; 0.001). IndentoPRO showed the highest correlation with SWE (r = 0.91), followed by MyotonPRO (r = 0.87), TCM (r = 0.85), and Durometer (r = 0.78). TCM exhibited the highest predictive value (R2 = 0.502) and most consistent performance across diabetic regions. The developed phantom models offer a standardized platform for evaluating stiffness assessment tools. While SWE remains the reference standard, mechanical devices, particularly TCM and IndentoPRO, demonstrated valid and reproducible performance. This phantom-based approach holds promise for supporting medical device development, regulatory validation, and preclinical testing in diabetic foot biomechanics.

Motor expertise modulates cortical activation during imagery of simple and complex actions

Motor imagery (MI) engages neural systems that overlap with actual movement and is widely used in sport and rehabilitation. Yet conflicting findings suggest that experts show either reduced (neural efficiency) or increased (vivid simulation) brain activation during MI. We hypothesized that task complexity moderates this effect. Using fNIRS, we compared experts and novices during MI of simple versus complex soccer actions. Experts showed lower activation for simple tasks but higher activation for complex ones, while novices showed the opposite pattern. These findings unify opposing accounts of expertise, revealing that expert brains adaptively scale simulation to task demands. This has practical implications for optimizing MI-based training across skill levels.

Dynamic weight clustered federated learning for IoT DDoS attack detection