Design Unsaturated Selenium Coordinated NbSe2-x as Multifunctional Sulfur Electrocatalyst toward Fast and Durable Sulfur Reduction Reaction.

Lithium-sulfur (Li-S) battery are considered as the next generation energy storage system owing to their ultra-high theoretical specific capacity and energy density. However, the commercialization of Li-S battery is still hindered by the intrinsically low conductivity of sulfur, sluggish catalytic conversion and notorious shuttle effect of polysulfides. The implantation of defects in sulfur electrocatalyst can effectively increase its conductivity and catalytic efficiency of lithium polysulfides, but the current mainstream defective materials are limited and lack of in-depth research. Herein, a defective niobium selenide (NbSe2-x) nanosheet sulfur electrocatalyst is constructed with enriched selenium defects, which demonstrates strong interaction with sulfur species, endowing NbSe2-x with rapid and reliable sulfur reduction reaction. As a result, the Li-S cell with NbSe2-x exhibits excellent multiplicative performance in both coin cell and pouch cell, which maintains stable cycling for over 2000 cycles under 5 C, corresponding to a low-capacity fading rate of 0.024% per cycle. Ah level pouch cell is also fabricated, showing a decent energy density of 378 Wh kg-1. This creative strategy not only emphasizes the importance of selenium defect engineering in Li-S batterie toward practical application, but also enlightens the material engineering to realize superior performance in related energy storage and conversion area.

Designing Cooperative Ion Transport Pathway in Ultra-Thin Solid-State Electrolytes toward Practical Lithium Metal Batteries.

Solid polymer electrolytes (SPEs) are promising for high-energy-density solid-state Li metal batteries due to their decent flexibility, safety, and interfacial stability. However, their development was seriously hindered by the interfacial instability and limited conductivity, leading to inferior electrochemical performance. Herein, we proposed to design ultra-thin solid-state electrolyte with long-range cooperative ion transport pathway to effectively increase the ionic conductivity and stability. The impregnation of PVDF-HFP inside pores of fluorinated covalent organic framework (CF3-COF) can disrupt its symmetry, rendering rapid ion transportation and inhibited anion immigration. The functional groups of CF3-COF can interact with PVDF-HFP to form fast Li+ transport channels, which enables the uniform and confined Li+ conduction within the electrolyte. The introduction of CF3-COF also enhances the mechanical strength and flexibility of SPEs, as well as ensures homogeneous Li deposition and inhibited dendrite growth. Hence, a remarkably high conductivity of 1.21×10-3 S cm-1 can be achieved. Finally, the ultra-thin SPEs with an extremely long cycle life exceed 9000 h can be obtained while the NCM523/Li pouch cell demonstrates a high capacity of 760 mAh and 96 % capacity retention after cycling, holding great promises to be utilized for practical solid-state Li metal batteries.

Substantia Innominata Glutamatergic Neurons Modulate Sevoflurane Anesthesia in Male Mice.

BACKGROUND: Accumulated evidence suggests that brain regions that promote wakefulness also facilitate emergence from general anesthesia (GA). Glutamatergic neurons in the substantia innominata (SI) regulate motivation-related aversive, depressive, and aggressive behaviors relying on heightened arousal. Here, we hypothesize that glutamatergic neurons in the SI are also involved in the regulation of the effects of sevoflurane anesthesia. METHODS: With a combination of fiber photometry, chemogenetic and optogenetic tools, behavioral tests, and cortical electroencephalogram recordings, we investigated whether and how SI glutamatergic neurons and their projections to the lateral hypothalamus (LH) regulate sevoflurane anesthesia in adult male mice. RESULTS: Population activity of glutamatergic neurons in the SI gradually decreased upon sevoflurane-induced loss of consciousness (LOC) and slowly returned as soon as inhalation of sevoflurane discontinued before recovery of consciousness (ROC). Chemogenetic activation of SI glutamatergic neurons dampened the animals' sensitivity to sevoflurane exposure, prolonged induction time (mean ± standard deviation [SD]; 389 ± 67 seconds vs 458 ± 53 seconds; P = .047), and shortened emergence time (305 seconds, 95% confidence interval [CI], 242-369 seconds vs 207 seconds, 95% CI, 135-279 seconds; P = .004), whereas chemogenetic inhibition of these neurons facilitated sevoflurane anesthesia. Furthermore, optogenetic activation of SI glutamatergic neurons and their terminals in LH induced cortical activation and behavioral emergence from different depths of sevoflurane anesthesia. CONCLUSIONS: Our study shows that SI glutamatergic neuronal activity facilitates emergence from sevoflurane anesthesia and provides evidence for the involvement of the SI-LH glutamatergic pathway in the regulation of consciousness during GA.

Effects of acupuncture combined with trunk strengthening training on balance and gait abilities in stroke hemiplegic patients.

This study aimed to observe the effects of acupuncture combined with trunk strengthening training on balance and gait abilities in stroke hemiplegic patients. Sixty stroke hemiplegic patients were selected and randomly divided into a treatment group and a control group, with 30 patients in each group. The control group received conventional rehabilitation training and trunk strengthening exercises, while the treatment group received acupuncture in addition to the same interventions. Before and after 8 weeks of treatment, patients were assessed using the Holden Functional Ambulation Categories and Berg Balance Scale, and measurements were taken for step length, step width, and gait speed. Prior to treatment, there were no significant differences in Holden scores, Berg scores, step length, step width, or gait speed between the 2 groups (P > .05). After 8 weeks of treatment, significant improvements were observed in the aforementioned parameters in both groups (P < .05), with the acupuncture group showing significantly greater improvement compared to the control group (P < .05). Acupuncture combined with trunk strengthening training can significantly improve balance and gait impairments in stroke hemiplegic patients.

A novel Saclayvirus Acinetobacter baumannii phage genomic analysis and effectiveness in preventing pneumonia.

Acinetobacter baumannii, which is resistant to multiple drugs, is an opportunistic pathogen responsible for severe nosocomial infections. With no antibiotics available, phages have obtained clinical attention. However, since immunocompromised patients are often susceptible to infection, the appropriate timing of administration is particularly important. During this research, we obtained a lytic phage vB_AbaM_P1 that specifically targets A. baumannii. We then assessed its potential as a prophylactic treatment for lung infections caused by clinical strains. The virus experiences a period of inactivity lasting 30 min and produces approximately 788 particles during an outbreak. Transmission electron microscopy shows that vB_AbaM_P1 was similar to the Saclayvirus. Based on the analysis of high-throughput sequencing and bioinformatics, vB_AbaM_P1 consists of 107537 bases with a G + C content of 37.68%. It contains a total of 177 open reading frames and 14 tRNAs. No antibiotic genes were detected. In vivo experiments, using a cyclophosphamide-induced neutrophil deficiency model, tested the protective effect of phage on neutrophil-deficient rats by prophylactic application of phage. The use of phages resulted in a decrease in rat mortality caused by A. baumannii and a reduction in the bacterial burden in the lungs. Histologic examination of lung tissue revealed a decrease in the presence of immune cells. The presence of phage vB_AbaM_P1 had a notable impact on preventing A. baumannii infection, as evidenced by the decrease in oxidative stress in lung tissue and cytokine levels in serum. Our research offers more robust evidence for the early utilization of bacteriophages to mitigate A. baumannii infection. KEY POINTS: •A novel Saclayvirus phage infecting A. baumannii was isolated from sewage. •The whole genome was determined, analyzed, and compared to other phages. •Assaying the effect of phage in preventing infection in neutrophil-deficient models.

In vivo efficacy of phage cocktails against carbapenem resistance Acinetobacter baumannii in the rat pneumonia model.

Acinetobacter baumannii, an opportunistic pathogen, poses a significant threat in intensive care units, leading to severe nosocomial infections. The rise of multi-drug-resistant strains, particularly carbapenem-resistant A. baumannii, has created formidable challenges for effective treatment. Given the prolonged development cycle and high costs associated with antibiotics, phages have garnered clinical attention as an alternative for combating infections caused by drug-resistant bacteria. However, the utilization of phage therapy encounters notable challenges, including the narrow host spectrum, where each phage targets a limited subset of bacteria, increasing the risk of phage resistance development. Additionally, uncertainties in immune system dynamics during treatment hinder tailoring symptomatic interventions based on patient-specific states. In this study, we isolated two A. baumannii phages from wastewater and conducted a comprehensive assessment of their potential applications. This evaluation included sequencing analysis, genome classification, pH and temperature stability assessments, and in vitro bacterial inhibition assays. Further investigations involved analyzing histological and cytokine alterations in rats undergoing phage cocktail treatment for pneumonia. The therapeutic efficacy of the phages was validated, and transcriptomic studies of rat lung tissue during phage treatment revealed crucial changes in the immune system. The findings from our study underscore the potential of phages for future development as a treatment strategy and offer compelling evidence regarding immune system dynamics throughout the treatment process.IMPORTANCEDue to the growing problem of multi-drug-resistant bacteria, the use of phages is being considered as an alternative to antibiotics, and the genetic safety and application stability of phages determine the potential of phage application. The absence of drug resistance genes and virulence genes in the phage genome can ensure the safety of phage application, and the fact that phage can remain active in a wide range of temperatures and pH is also necessary for application. In addition, the effect evaluation of preclinical studies is especially important for clinical application. By simulating the immune response situation during the treatment process through mammalian models, the changes in animal immunity can be observed, and the effect of phage therapy can be further evaluated. Our study provides compelling evidence that phages hold promise for further development as therapeutic agents for Acinetobacter baumannii infections.

Ammonium Additive Engineering in Antisolvents for Improving Perovskite/Charge-Transport-Layer Interfaces toward Efficient Lead-Tin Alloyed Perovskite Solar Cells.

Although significant advancements have been achieved in lead-tin (Pb-Sn) alloyed perovskite solar cells (PSCs), their power conversion efficiency (PCE) remains inferior to that of their Pb-based counterparts, primarily due to higher open-circuit voltage (Voc) losses and lower fill factors (FFs). Herein, we report both perovskite top and bottom interfacial improvements by incorporating a facile fluorophenylethylammonium iodide (p-FPEAI)/ethyl acetate (EA) solution during the film crystal growth. Based on the analysis of perovskite crystallization, film growth, and strain relaxation, the mechanisms behind these interfacial improvements have been well understood. Furthermore, p-FPEAI could reduce the defect density and nonradiative recombination losses, thus attributing to the improved Voc and FF. Finally, the treated device achieved a PCE of 20.14% with a Voc of up to 0.84 V, which is among the highest reported values so far for Pb-Sn alloyed PSCs without additional precursor additives. In addition, the unencapsulated p-FPEAI-treated device maintained its initial efficiency of approximately 92% after being kept in a nitrogen atmosphere for 1 month, in contrast to the control device which retained only 30% of its initial value. Our findings provide a comprehension for understanding the effect of bulky cations as antisolvents on fabricating highly efficient Pb-Sn alloyed perovskite solar cells.

Over 19% Efficiency Perovskite Solar Modules by Simultaneously Suppressing Cation Deprotonation and Iodide Oxidation.

Perovskite solar cells (PSCs) based on sputtered nickel oxide (NiOx) hole transport layer have emerged as promising configuration due to their good stability, cost-effectiveness, and scalability. However, the adverse chemical redox reaction at the NiOx/perovskite interface remains an ever-present problem that has not yet been well solved. To address this issue before, the problems that cation deprotonation and iodide oxidation that occurred in precursor solution easily result in the interfacial chemical reaction should be prevented. Hence, we report an efficient strategy to simultaneously suppress the interfacial reaction and stabilize the precursor solution by incorporating a reducing and weakly acidic stabilizer, l-ascorbic acid (l-AA). l-AA can reduce I2 generated in the precursor solution and during the interfacial reaction to I-. Furthermore, the protons ionized by adjacent enol hydroxyl groups in l-AA effectively impede the deprotonation of organic cations in the precursor solution as well as at the NiOx/perovskite interface resulting from the chemical reaction. Attributing to the improved crystallization of the perovskite film and the suppression of the interfacial reaction by l-AA, the inverted PSC based on such good light absorber achieves an impressive power conversion efficiency (PCE) of 22.72% along with a high open-circuit voltage of 1.19 V. Notably, further introducing l-AA into the large-area solar modules by the slot-die coating method in air enables a remarkable PCE of 19.17%, which reaches one of the highest PCEs reported for inverted perovskite solar modules (PSMs) (active area >50 cm2) to date. l-AA located at the buried interface also forms a barrier layer that can prevent undesirable chemical reactions at the NiOx/perovskite interface, significantly enhancing the device stability of solar cells and PSMs. These findings in our work provide important guidance for improving the NiOx/perovskite interface and the fabrication of highly efficient, low-cost, and large-area PSMs.

Brain glucose induces tolerance of Cryptococcus neoformans to amphotericin B during meningitis.

Antibiotic tolerance is the ability of a susceptible population to survive high doses of cidal drugs and has been shown to compromise therapeutic outcomes in bacterial infections. In comparison, whether fungicide tolerance can be induced by host-derived factors during fungal diseases remains largely unknown. Here, through a systematic evaluation of metabolite-drug-fungal interactions in the leading fungal meningitis pathogen, Cryptococcus neoformans, we found that brain glucose induces fungal tolerance to amphotericin B (AmB) in mouse brain tissue and patient cerebrospinal fluid via the fungal glucose repression activator Mig1. Mig1-mediated tolerance limits treatment efficacy for cryptococcal meningitis in mice via inhibiting the synthesis of ergosterol, the target of AmB, and promoting the production of inositolphosphorylceramide, which competes with AmB for ergosterol. Furthermore, AmB combined with an inhibitor of fungal-specific inositolphosphorylceramide synthase, aureobasidin A, shows better efficacy against cryptococcal meningitis in mice than do clinically recommended therapies.

Highly Efficient and Stable ITO-Free Organic Solar Cells Based on Squaraine N-Doped Quaternary Bulk Heterojunction.

Simultaneously achieving high efficiency and robust device stability remains a significant challenge for organic solar cells (OSCs). Solving this challenge is highly dependent on the film morphology of the bulk heterojunction (BHJ) photoactive blends; however, there is a lack of rational control strategy. Herein, it is shown that the molecular crystallinity and nanomorphology of nonfullerene-based BHJ can be effectively controlled by a squaraine-based doping strategy, leading to an increase in device efficiency from 17.26% to 18.5% when doping 2 wt% squaraine into the PBDB-TF:BTP-eC9:PC71 BM ternary BHJ. The efficiency is further improved to 19.11% (certified 19.06%) using an indium-tin-oxide-free column-patterned microcavity (CPM) architecture. Combined with interfacial modification, CPM quaternary OSC excitingly shows an extrapolated lifetime of ≈23 years based on accelerated aging test, with the mechanism behind enhanced stability well studied. Furthermore, a flexible OSC module with a high and stable efficiency of 15.2% and an overall area of 5 cm2 is successfully fabricated, exhibiting a high average output power for wearable electronics. This work demonstrates that OSCs with new design of BHJ and device architecture are highly promising to be practical relevance with excellent performance and stability.

Optogenetic and pharmacological interventions link hypocretin neurons to impulsivity in mice.

Neurons in the lateral hypothalamus expressing the neuropeptide Hypocretin, also known as orexin, are known critical modulators of arousal stability. However, their role in the different components of the arousal construct such as attention and decision making is poorly understood. Here we study Hypocretin neuronal circuit dynamics during stop action impulsivity in a Go/NoGo task in mice. We show that Hypocretin neuronal activity correlates with anticipation of reward. We then assessed the causal role of Hypocretin neuronal activity using optogenetics in a Go/NoGo task. We show that stimulation of Hypocretin neurons during the cue period dramatically increases the number of premature responses. These effects are mimicked by amphetamine, reduced by atomoxetine, a norepinephrine uptake inhibitor, and blocked by a Hypocretin receptor 1 selective antagonist. We conclude that Hypocretin neurons have a key role in the integration of salient stimuli during wakefulness to produce appropriate and timely responses to rewarding and aversive cues.

Effect of combination drug therapy during cesarean section in preventing postpartum hemorrhage for women with hypertensive disorder complicating pregnancy.

The study was carried out to observe the effect of combination drug therapy during cesarean section in preventing postpartum hemorrhage for women with hypertensive disorder complicating pregnancy (HDCP). The 180 women who had been treated in our hospital for HDCP were enrolled and randomly divided into observation group (sublingual administration of carboprost combined with oxytocin treatment (20IU oxytocin and small pot drip of 10IU oxytocin after delivery) and control group (1mg of carboprost when the fetal head came out and then applied with intramuscular injection of 20IU oxytocin), each containing 90. The comparison of postpartum hemorrhage situation between two groups was carried out. Compared with control group, the observation group had significantly lower intraoperative blood loss and postoperative 1h blood loss, p<0.0, but similar postoperative 2-24h blood loss, p>0.05; in observation, there were 6 cases of postpartum hemorrhage, while the number in control group was 20 cases. The two groups had no difference in blood pressure after treatment, p>0.05.The combination drug therapy during cesarean section is effective and reliable in preventing postpartum hemorrhage for women with HDCP.

Natural and anthropogenic factors and their interactions drive stream community integrity in a North American river basin at a large spatial scale.

Urbanization, agriculture, and other human activities can exert considerable influence on the health and integrity of stream ecosystems. These influences vary greatly over space, time, and scale. We investigated trends in stream biotic integrity over 19 years (1997-2016) in relation to natural and anthropogenic factors in their spatial context using data from a stream biomonitoring program in a region dominated by agricultural land use. Macroinvertebrate and fish diversity and abundance data were used to calculate four multimetric indices (MMIs) that described biotic integrity of streams from 1997 to 2016. Boosted regression trees (BRT), a machine learning technique, were used to model how stream integrity responded to catchment-level natural and anthropogenic drivers including land use, human population density, road density, runoff potential, and natural factors such as latitude and elevation. Neither natural nor anthropogenic factors were consistently more influential on the MMIs. Macroinvertebrate indices were most responsive to time, latitude, elevation, and road density. Fish indices were driven mostly by latitude and longitude, with agricultural land cover among the most influential anthropogenic factors. We concluded that 1) stream biotic integrity was mostly stable in the study region from 1997 to 2016, although macroinvertebrate MMIs had decreased approximately 10% since 2010; 2) stream biotic integrity was driven by a mix of factors including geography, human activity, and variability over yearly time intervals; 3) MMI responses to environmental drivers were nonlinear and often nonmonotonic; 4) MMI composition could influence causal inferences; and 5) although our findings were mostly consistent with the literature on drivers of stream integrity, some commonly seen patterns were not evident. Our findings highlight the utility of large-scale, publicly available spatial data for understanding drivers of stream biodiversity and illustrate some potential pitfalls of large scale, integrative analyses.

Lateral hypothalamic galanin neurons are activated by stress and blunt anxiety-like behavior in mice.

Despite the prevalence of anxiety disorders, the molecular identity of neural circuits underlying anxiety remains unclear. The lateral hypothalamus (LH) is one brain region implicated in the regulation of anxiety, and our recent data found that chemogenetic activation of LH galanin neurons attenuated the stress response to a novel environment as measured by the marble burying test. Thus, we hypothesize that LH galanin neurons may contribute to anxiety-related behavior. We used chemogenetics and fiber photometry to test the ability of LH galanin neurons to influence anxiety and stress-related behavior. Chemogenetic activation of LH galanin neurons significantly decreased anxiety-like behavior in the elevated plus maze, open field test, and light dark test. However, LH galanin activation did not alter restraint stress induced HPA activation or freezing behavior in the fear conditioning paradigm. In vivo calcium monitoring by fiber photometry indicated that LH galanin neurons were activated by anxiogenic and/or stressful stimuli including tail suspension, novel mouse interaction, and predator odor. Further, in a fear conditioning task, calcium transients strongly increased during foot shock, but were not affected by the unconditioned stimulus tone. These data indicate that LH galanin neurons both respond to and modulate anxiety, with no influence on stress induced HPA activation or fear behaviors. Further investigation of LH galanin circuitry and functional mediators of behavioral output may offer a more refined pharmacological target as an alternative to first-line broad pharmacotherapies such as benzodiazepines.

Hyperexcitable arousal circuits drive sleep instability during aging.

Sleep quality declines with age; however, the underlying mechanisms remain elusive. We found that hyperexcitable hypocretin/orexin (Hcrt/OX) neurons drive sleep fragmentation during aging. In aged mice, Hcrt neurons exhibited more frequent neuronal activity epochs driving wake bouts, and optogenetic activation of Hcrt neurons elicited more prolonged wakefulness. Aged Hcrt neurons showed hyperexcitability with lower KCNQ2 expression and impaired M-current, mediated by KCNQ2/3 channels. Single-nucleus RNA-sequencing revealed adaptive changes to Hcrt neuron loss in the aging brain. Disruption of Kcnq2/3 genes in Hcrt neurons of young mice destabilized sleep, mimicking aging-associated sleep fragmentation, whereas the KCNQ-selective activator flupirtine hyperpolarized Hcrt neurons and rejuvenated sleep architecture in aged mice. Our findings demonstrate a mechanism underlying sleep instability during aging and a strategy to improve sleep continuity.

Regulating crystallization dynamics and crystal orientation of methylammonium tin iodide enables high-efficiency lead-free perovskite solar cells.

Tin (Sn)-based perovskite solar cells (PSCs) have attracted much attention because they are more environmentally friendly than lead-based PSCs. However, the fast crystallization of Sn-based perovskite films and the easy oxidation of Sn2+ to Sn4+ hinder the improvement of their efficiency and stability. In this work, ethylammonium bromide (EABr) was added to methylammonium tin iodide (MASnI3) perovskite precursor solution to regulate the crystallization dynamics and improve the film morphology. The results show that the large EA+ ions slow down the crystallization process of Sn-based perovskites and form a smooth perovskite film with high crystallinity, while the added Br- anions further improved the crystallinity and orientation of the perovskite film. Under the combined action of EA+ and Br- ions, the as-produced PSCs achieved a champion power conversion efficiency (PCE) of 9.59%. The EABr additive also retarded the oxidation of Sn2+, and the solar cell device maintained 93% of its initial efficiency after 30 days in a nitrogen-filled glove box without being encapsulated. This work provides a new strategy for the realization of high-efficiency Sn-based PSCs.

Zwitterion-Assisted Crystal Growth of 2D Perovskites with Unfavorable Phase Suppression for High-Performance Solar Cells.

Despite two-dimensional (2D) Ruddlesden-Popper-phase layered perovskites (RPLPs) exhibiting excellent environmental stability, most solar cells based on 2D RPLP films are fabricated in a controlled inert atmosphere. Meanwhile, the poor charge transport of 2D RPLP films owing to the unfavorable phase arrangement and defects limits the efficiency of 2D RPLP solar cells. Here, we fabricate high-efficiency 2D RPLP solar cells in ambient air assisted by a zwitterion (ZW) additive. We show that the ZW additive suppresses the formation of the bottom 2D phases (n ≤ 2) and the top 3D-like phases in 2D RPLP films. These 2D phases usually grow parallel to the substrate and act as trap sites that inhibit charge transport in the vertical direction. The 3D-like phases, on the other hand, aggravate the long-term stability due to the intrinsic instability of MA+ cations. With improved phase distribution, crystal orientation, and reduced trap states in 2D RPLP films, efficient charge transport is obtained. Finally, a record-high open-circuit voltage (Voc) of 1.19 V and a power conversion efficiency of 17.04% with an enhanced stability are achieved for (BA0.9PEA0.1)2MA3Pb4I13-based (n = 4) solar cells fabricated under high humidity (∼65% RH).