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A sexually dimorphic neuronal cluster in the mouse medial amygdala responds to male sexual status

Increasing scientific interest has been directed toward understanding sexual dimorphism in the brain. Although several brain structures exhibit masculine or feminine characteristics, strictly binary anatomical feature, comparable to those observed in genitalia, has been rarely identified. In this study, we identified a dense, sexually dimorphic cluster of neurons in the posterodorsal medial amygdala (MeApd), which we named DIMPLE (Dimorphic IEGs Medial Posterodorsal amygdala Labeled Ensemble) that exhibited a remarkable binary pattern of c-fos promoter activation. Using the TRAP2 (Targeted Recombination in Active Populations) transgenic mouse model, we found that it was consistently labeled in all females, regardless of age or sexual experience. In contrast, DIMPLE labeling was absent in adult virgin males but present both prior to weaning and following mating. Surgical removal of gonads (ovariectomy or orchiectomy) did not alter the labeling pattern of DIMPLE in either sex. Interestingly, a single intraperitoneal injection of prolactin, a hormone that increases in males after mating, induced DIMPLE labeling in virgin males. However, treatment with cabergoline, a potent inhibitor of prolactin secretion, did not prevent DIMPLE labeling in females or in postmating males. Given the established role of the MeApd in social and reproductive behaviors, we hypothesize that DIMPLE may support neural mechanisms underlying female-typical behavior and potentially contribute to postmating behavioral shifts in males.

Correction: Dementia and autopsy-verified causes of death in racially-diverse older Brazilians

Magnetotelluric forward modeling on fine grid via deep learning with physical information constraints

The EPS-I exopolysaccharide transforms <i>Ralstonia</i> wilt pathogen biofilms into viscoelastic fluids for rapid dissemination in planta

Ralstonia solanacearum species complex (RSSC) pathogens cause destructive plant wilt diseases of a wide variety of crops, leading to significant agricultural losses worldwide. These bacteria rapidly spread through the water-transporting xylem where they grow prolifically and produce abundant biofilm that clogs xylem vessels. To understand RSSC biofilm behavior in planta, we examined their complex fluid mechanics. Rheological analyses revealed that unlike all previously analyzed microbial biofilms, RSSC biofilms are shear-thinning, viscoelastic fluids at physiologically relevant shear forces. To determine which factors confer these unique mechanics, we analyzed biofilms of bacterial mutants with altered biofilm components. Genetic analysis demonstrated that development of the viscous-dominant biofilms required production of EPS-I, an amphiphilic exopolysaccharide that is a major virulence factor for all RSSC pathogens. We show that EPS-I confers “biofilm mobility”, which allows wild-type RSSC colonies to passively expand when deformed. Despite its high metabolic cost, bioassays demonstrated that EPS-I production conferred a net fitness benefit where biofilm mobility allowed the pathogen to spread and access more nutrients in complex environments like xylem vessels. The RSSC are a monophyletic lineage of aggressive plant wilt pathogens, and our evolutionary hypothesis testing suggests the origin of the eps biosynthetic gene cluster coincides with the emergence of wilt pathogenesis in the RSSC ancestor. Furthermore, comparative physiological assays demonstrated that biofilm mobility is unique to the RSSC within the genus Ralstonia . In summary, EPS-I production is a key evolutionary innovation that enables RSSC dispersal and virulence by conferring unique biofilm mechanics.

Tunicates have a complex, highly dynamic TNF superfamily

Genes of the Tumor Necrosis Factor Superfamily (TNFSF) encode proteins with critical roles in cell signaling in animals, particularly in immunity and development. The evolution of the TNF superfamily remains poorly understood. This study demonstrates that tunicates possess a much more complex TNF superfamily than previously assumed. Some species have a large number of TNFSF genes, up to 14, due to frequent, independent tandem duplications. Significantly, this number exceeds that observed in many vertebrates (e.g., all characterized cyclostomes, as well as some birds and reptiles). As in vertebrates, the TNF superfamily of tunicates is capable of rapid evolutionary change. All 24 model tunicate species analyzed have different sets of TNFSF genes and even closely related species often have quite distinct TNF superfamilies. A comparison of tunicate and vertebrate data suggests that four TNFSF genes were present in the last common ancestor of both lineages. One of these genes was subsequently lost while the other three underwent independent duplications in early tunicate evolution. Six TNFSF genes were likely present in the common ancestor of all tunicates except perhaps appendicularians, for which data remain inconclusive. These results are consistent with the current model of how the TNFSF vertebrate genes emerged and evolved, except that whole-genome duplications played a significant role in expanding the family in vertebrates but not in tunicates. Transcription data obtained from Ciona intestinalis type A ( C. robusta ) indicate that several distantly related TNFSF genes share similar patterns of expression during development and in adults. Gene expression data are compatible with TNFSF genes having multiple roles, some of them in the innate immune system. Their involvement in immune defense may explain the rapid changes in TNFSF gene number observed in both tunicates and vertebrates.

Multipassage Landau-Zener tunneling oscillations in the dual dressing of atomic qubits

A surface-exposed cardiolipin synthase provides an unexpected paradigm for maintaining the Gram-negative outer membrane

Gram-negative bacteria have long been thought to confine primary glycerophospholipid synthesis to the inner membrane (IM). Here, we challenge this paradigm by identifying ClsO, an outer membrane (OM) lipoprotein from Acinetobacter baumannii that functions as a cardiolipin synthase. In contrast to canonical cardiolipin synthases, which are restricted to the IM, ClsO is surface-exposed and deposits cardiolipin into the outer leaflet of the OM, colocalizing with Acinetobacter lipooligosaccharide. Loss of ClsO sensitizes cells to membrane disrupting agents, such as bile salts, and key antibiotics, implicating ClsO in OM barrier integrity. ClsO activity increases when mislocalized glycerophospholipids accumulate at the cell surface, such as in cells lacking Mla (maintenance of lipid asymmetry) system, consistent with a surface-active site mechanism. Engineering mutations in ClsO that prevent its trafficking to the OM was found to abolish nearly all enzymatic activity. Remarkably, we found that ClsO homologs are widespread across Proteobacteria and confirmed several to be functional cardiolipin synthases, indicating a conserved strategy of surface lipid remodeling. These findings redefine the spatial organization of lipid metabolism in Gram-negative bacteria and reveal an adaptive mechanism to maintain OM integrity when membrane asymmetry is compromised.

Effect of esketamine-based patient-controlled intravenous analgesia on postoperative pain and quality of recovery after video-assisted thoracoscopic lobectomy: A prospective, double-blind, randomized controlled trial

Objective This double-blinded randomized study aimed to investigate the effects of esketamine-based patient-controlled intravenous analgesia (PCIA) on postoperative analgesia and quality of recovery in patients undergoing video-assisted thoracoscopic (VATS) lobectomy. Methods Patients undergoing selective VATS lobectomy were enrolled and randomly assigned (1:1) to receive PICA with 1.5 mg/kg esketamine (group K) or 1.5 mg/kg sufentanil (group S). Pain intensity was evaluated using the short-form of the McGill Pain Questionnaire (SF-MPQ) and the visual analog scale (VAS). The primary endpoint was the SF-MPQ score of patients on postoperative day 1. Results Between December 2021 and May 2022, 84 eligible patients received the allocated treatment, with 80 patients (40 per group) ultimately included in the analysis. The total SF-MPQ score in group K was lower than that in group S on postoperative day 1 ( P  &lt; 0.001) and day 2 ( P  &lt; 0.001). Additionally, the VAS-rest, VAS-movement and patients’ depression-related scores in group K were all significantly lower than those in group S on postoperative day 1 ( P  = 0.012, P  = 0.008 and P  = 0.009, respectively) and day 2 (all P  &lt; 0.001), whereas the postoperative recovery quality was significantly higher in group K than that in group S on postoperative days 1 and 2 (both P  &lt; 0.001). A lower incidence of total adverse events (AEs) was observed in group K than in group S (15% vs. 35%, P  = 0.039). Conclusion The use of 1.5 mg/kg esketamine in PCIA for postoperative analgesia in patients undergoing VATS lobectomy showed a promising analgesic effect and improved perioperative depression and postoperative recovery quality, with no severe AEs observed.

Correction: Decomposition of socioeconomic inequalities in zero-dose children aged 12–23 months in India

Disorder-induced stress–flow misalignment in soft glassy materials revealed using multidirectional shear

Controlling the mechanical response of soft glassy materials—such as emulsions, foams, and colloidal suspensions—is key for many industrial processes. While their steady-state flow behavior is reasonably well understood, their response to complex flow histories, as encountered in operations like pumping or mixing, remains poorly known. Using a custom multiaxis shear apparatus that enables arbitrary changes in flow direction, we investigate how shear history influences the mechanical behavior of a model soft glassy system. We uncover a transient shear response orthogonal to the applied shear direction, together with an anisotropic yield surface. These effects point to an underlying anisotropic distribution of internal stresses imprinted by previous deformation. To rationalize this behavior, we use a mesoscopic elastoplastic model, demonstrating that local mechanical disorder governs the emergence of macroscopic stress–flow misalignment. Our findings offer a route to experimentally probe the distribution of local yield stresses in soft glassy materials.

Adult airway management in ICU and regular floors: A prospective study as part of a healthcare improvement initiative in a tertiary care center

Background Despite recent advancements, airway management outside the operating room (OR) remains a challenging task and is associated with a high rate of complications. The first pass success rate at our institution was low. We developed a standardized multidisciplinary protocol to improve it as part of a healthcare improvement initiative. Methods Following the implementation of the protocol, this prospective observational study was conducted on patients over 18 years old requiring intubation by anesthesia providers on regular floors and in intensive care units. The primary outcome was the first-attempt success rate of endotracheal intubation. Secondary outcomes included total number of attempts, time to successful intubation, equipment and medications used, and occurrence of adverse events such as severe hypotension (systolic blood pressure (SBP) ≤80 mmHg), severe hypoxemia (SpO2 ≤ 85%), and cardiac arrest. Results All 199 patients were successfully intubated, with 184 patients (92.5%) intubated at first attempt. Twenty-four patients had a baseline SBP ≤ 80 mmHg, with 35 additional patients experiencing a drop in blood pressure during intubation. Thirty-eight patients had a baseline SpO 2  ≤ 85%, with 11 additional patients experiencing desaturation during intubation. Two patients had cardiac arrest during intubation and were resuscitated. Multivariable logistic regression identified SpO2 ≤ 85% as the only predictor of hypoxemia (OR: 22.85, 95%CI: 9.07–57.55, P &lt; 0.001) and baseline hypotension as the only predictor of hypotension during intubation (OR: 32.43, 95%CI: 7.14–147.33, P &lt; 0.001). Conclusion Implementing a standardized multidisciplinary protocol that includes highly experienced anesthesia providers and the use of muscle relaxants resulted in a very high first-attempt intubation success rate in critically ill patients, with the persistence of a high incidence of adverse events. Our successful approach may inform other policymakers about best practices for safe intubation in high-risk patients, highlighting the need for strategies to mitigate hemodynamic and respiratory complications and encouraging them to implement airway healthcare improvement initiatives in their institutions.

Optimized gradient of lyophilized platelet-rich plasma in biomimetic 3D-printed triphasic scaffold based on alginate and gelatin for osteochondral tissue engineering

Abstract This study developed a 3D-printed, triphasic (subchondral bone, calcified, and articular cartilage) scaffold using biological macromolecule-based bioinks to support the chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). A subchondral bone layer was formed by blending various concentrations of graphene oxide (GO) (1% and 2% w/w) into an alginate (Alg) and gelatin (Gel) bioink, two natural biopolymers known for their biocompatibility and biodegradability. Following mechanical and biocompatibility assessments, the 1% GO concentration was selected and applied consistently through the subchondral and calcified cartilage layers. In contrast, the gradient of lyophilized platelet-rich plasma (PRP) powder was adjusted to 1%, 2%, and 3% (w/v) to more accurately replicate the characteristics of calcified and articular cartilage. Triphasic scaffolds with different PRP gradients were evaluated for water absorption, biodegradability, rheological behavior, stem cell viability, and chondroinductive activity. The results indicated that 3D-printed triphasic scaffolds containing 1% or 2% PRP exhibited favorable biomechanical properties, with no significant differences between the two concentrations. However, scaffolds with 2% PRP facilitated the attachment, proliferation, and survival of BM-MSCs, as indicated by an increase in the expression of cartilage-related genes and enhanced production of glycosaminoglycan (GAG), as confirmed through real-time PCR and Alcian Blue staining, respectively.

Slippage reconfiguration of trinucleotide repeat hairpins impedes resolution by human replication protein A

Abnormal expansions of trinucleotide repeats (TNRs) are a major cause of neurodegenerative diseases, often driven by the formation of stable hairpin structures that interfere with protein machineries in DNA cellular processes. On the other hand, human replication protein A (hRPA) plays a central role in stabilizing single-stranded DNA and resolution of secondary structures. Understanding how hRPA interacts with TNR hairpins has become crucial to uncovering the mechanisms that regulate TNR stability. Here, we employed single-molecule fluorescence resonance energy transfer to investigate the interaction between hRPA and CTG repeat hairpins of varying lengths. We found that blunt-end hairpins impede hRPA resolution, while the presence of a short overhang facilitates initial binding followed by invasion. At higher repeat lengths, hRPA binding induces partial hairpin resolution, followed by conformational slippage that restores blunt-end hairpin structures and hinders further progression. Hairpin resolution is coordinated by the interplay of the multiple dynamic binding modes of hRPA and the slippage reconfiguration of the TNR hairpins. Moreover, our results reveal a concentration- and stoichiometry-dependent resolution process, herein full resolution of TNR hairpins with pathologically relevant repeat lengths requires protein concentrations exceeding physiological levels, potentially contributing to disease pathogenesis.

Carbon nanotube and carbon dot mediated plasmid DNA delivery in cowpea leaves

CRISPR-Cas9 technology has been widely used as a key molecular biology tool for crop improvement. However, the advance of this technology has been hindered by host species- or genotype-dependent tissue culture protocols and poor transformation efficiencies. Recent research has shown that plasmid DNA delivered by single-walled carbon nanotubes (SWCNTs) and carbon dots (CDs) can diffuse through plant cell walls, enabling the transient expression of genetic material in plant tissues. However, such an experiment has not been performed in legumes, most of which are considered recalcitrant species for transformation. In this study, we aim to investigate the capability of a SWCNT or CD-based plasmid delivery system in expressing a target gene in cowpea ( Vigna unguiculata ) leaves via infiltration using the β-glucuronidase ( GUS ) reporter gene. Further, we aim to see the potential of SWCNTs and CDs for a CRISPR-Cas9 gene construct delivery system, with phytoene desaturase ( PDS ) as the target gene. Our results showed that SWCNTs and CDs can deliver the GUS reporter gene construct in the surrounding area near the site of the infiltration, which results in the temporary expression of GUS by observing the blue color in this area. Likewise, infiltration of the CRISPR-Cas9 vectors targeting the PDS gene for the knockout resulted in multiplex editing and large deletions within the target gene. Overall, our findings pave the way for overcoming conventional DNA delivery challenges. However, further research is needed to explore optimal germline targets for plant tissues to avoid chimerism and to allow for more efficient CRISPR-Cas9 editing resulting in heritable mutations.

A validation study comparing Cheetah monitor cardiac output to thermodilution cardiac output in patients with severe mitral regurgitation

Symmetry-protected topological polarons

Emergent quasiparticles in solids often exhibit unique topological properties as a result of the complex interplay between charge, orbital, spin, and lattice degrees of freedom. Among these quasiparticles, the polaron occupies a special place as the first known manifestation of the interaction between a fermion and a boson field. While polarons have been investigated for almost a century, whether these quasiparticles exhibit topological properties and why remain open questions. Here, we establish the universal symmetry principles governing the topology of polar textures in large polarons. Using a group-theoretic analysis, we identify four distinct classes of polar textures in time-reversal-invariant systems, and we show that they carry integer topological charges. We validate this classification by performing state-of-the-art first-principles calculations of materials representative of each class. For these materials, we compute the fingerprints of polaron topology in Huang diffuse scattering and propose ultrafast electron and X-ray scattering experiments to detect these quasiparticles.

Developing a simple, cost-effective proof-of-concept vaccine candidate against EHEC for cattle

Enterohemorrhagic Escherichia coli (EHEC) is a zoonotic pathogen responsible for severe human diseases, including hemorrhagic diarrhea and hemolytic uremic syndrome (HUS), primarily mediated by Shiga toxins (Stx). Intestinal colonization depends on the type III secretion system (T3SS), which induces attaching and effacing (A/E) lesions. Cattle are the main reservoir, and preharvest vaccines are key to reducing human exposure. In this work, we engineered a chimeric antigen EIT (EspA 36-192 -Intimin 653-935 -Tir 258-361 ) to be expressed in the periplasm of E. coli BL21, enabling simple extraction by thermal shock. To favor scalable production, the process avoids the use of antibiotics, chemical inducers, and mechanical disruption, while remaining compatible with standard infrastructure and low-cost adjuvants. Immunization of mice with an EIT-enriched periplasmic fraction (EIT-PF) induced strong antibody responses with enhanced functional activity against A/E pedestal formation in vitro , and accelerated clearance of experimental E. coli O157 infection in mice. A three-dose EIT-PF immunization was tested in cattle. Notably, a single EIT-PF dose elicited antibodies that recognized multiple EHEC serotypes and EPEC, as well as each chimera component, effectively interfering with T3SS-dependent pedestal formation in vitro . Our findings support EIT-PF as a broadly reactive, proof-of-concept vaccine candidate for cattle; further studies are required to assess efficacy under field conditions.

Exploring phytochemistry, antioxidant potential, essential oil profiling and bioactive profiling of Pogostemon mollis Benth. through GC–MS and UPLC-QTOF-MS/MS

Abstract The genus Pogostemon (Lamiaceae) is known for its diverse pharmacological and ethnomedicinal properties, which may be due to the presence of various bioactive constituents. This study investigates antioxidant potential, profiling of phytochemicals, essential oil and their derivatives from Pogostemon mollis Benth., and correlation among them. Plant parts were taken in fresh and dried forms, were extracted using methanol, acetone and distilled water through ultrasonication extraction method. Essential oil was obtained from the aerial parts through hydro-distillation with a Clevenger apparatus. Antioxidant activity by DPPH, FRAP, and ABTS, demonstrating significant radical scavenging and reducing power; dry aqueous leaf extract showing the highest inhibition (65.1 ± 0.11%) and the lowest in fresh aqueous stem extract (9.80 ± 0.24%). Total phenolic and flavonoid contents were checked for extracts, revealing maximum phenolic content in dry methanolic leaf extract (249.9 ± 0.47 mg GAE/g) and minimum in fresh acetonic root extract (64.12 ± 0.31 mg GAE/g). The highest flavonoid content was found in dry acetonic leaf extract (50.5 ± 0.00 mg RE/g), while the lowest was in fresh aqueous root extract (16.04 ± 0.49 mg RE/g). UPLC-QTOF-MS/MS revealed 99 bioactive compounds, such as anticancer (camptothecin), antiviral (zidovudine), flavonoid (luteolin), and terpenoid (nerolidol) agents. GC–MS identified 68 compounds in the essential oil, with major constituents including lupeol (6.33%), alpha-cyperone (7.15%), and caryophyllene oxide (7.23%). Significant correlations were found between total phenolic content, total flavonoid content, and antioxidant activities, highlighting the therapeutic potential of P. mollis for developing natural antioxidants and bioactive formulations.

Optimization via the strategic law of large numbers

This paper proposes a framework for the global optimization of a possibly multimodal continuous function in a bounded rectangular domain. We first show that global optimization is equivalent to an optimal (sampling) strategy formation in a two-armed decision model with known distributions, based on the strategic law of large numbers we establish. There are many optimal strategies in general. We show that a concrete strategy using the sign of the partial gradient of the unique solution to a parabolic partial differential equation (PDE) is asymptotically optimal. Motivated by these results, we propose a class of Strategic Monte Carlo Optimization (SMCO) algorithms, which uses a simple strategy that makes coordinate-wise two-armed decisions based on the signs of the partial gradient (or practically the first difference) of the objective function, without the need of solving PDEs. Under some sufficient conditions, we establish that our SMCO algorithm converges to a local optimizer from a single starting point, and to a global optimizer under a growing set of starting points. Extensive numerical studies demonstrate the suitability of our SMCO algorithms for global optimization well beyond the theoretical guarantees established herein. For a wide range of deterministic and random test functions with challenging landscapes (multimodal, nondifferentiable, discontinuous), our SMCO algorithms perform robustly well, even in high-dimensional ( d = 200 ∼ 1 , 000 ) settings. In fact, our algorithms outperform many state-of-the-art global optimizers, as well as local algorithms (with the same set of starting points as ours).

Body mass index is associated with hypoglycaemia in children with acute vomiting and dehydration

Background Healthy children from 7 months to 7 years are known to be at risk for developing hypoglycaemia during prolonged fasting, particularly during acute illness with decreased oral intake. Our study aimed to identify additional factors associated with hypoglycaemia in children with acute vomiting and dehydration. Methods Our retrospective single-centre study included 560 healthy children and adolescents (aged 29 days to 17.96 years) without known metabolic disorders admitted to hospital with dehydration due to acute illness with vomiting or poor oral intake. Historical and anthropometric parameters were evaluated as potential factors associated with hypoglycaemia. Results A total of 171 (30.5%) participants (aged 0.6–10.7, median 3.8 years) experienced hypoglycaemia (≤3.3 mmol/l). Besides known factors such as a higher degree of dehydration (OR 2.505, 95% CI 1.532–4.095) and complete absence of oral intake (OR 2.185, 95% CI 1.331–3.586), additional factors independently associated with hypoglycaemia included diarrhoea (OR 0.178, 95% CI 0.068–0.468) and lower body mass index (BMI) (OR 0.011, 95% CI 0.000–0.605). Children with hypoglycaemia had a significantly lower BMI (median 14.29 vs 15.46 kg/m 2 , p &lt; 0.001) than children without hypoglycaemia. Only one child with hypoglycaemia was obese. The highest rate of hypoglycaemia (37.5–51.6%) was observed in the 2–7-year age groups, who also had the lowest median BMI values (13.9–14.8). Conclusions Low BMI and absence of diarrhoea were associated with increased odds of hypoglycaemia. The typical BMI curve for children with physiologically low values at 2–7 years of age may partially explain the high incidence of hypoglycaemia in otherwise healthy children with decreased oral intake at this age.