Construction of a In2O3/ultrathin g-C3N4 S-scheme heterojunction for sensitive photoelectrochemical aptasensing of diazinon.

A single semiconductor-based photoelectrochemical (PEC) aptasensor usually faces a challenge of low sensitivity due to poor solar energy utilization and a high photogenerated carrier recombination rate. Herein, an ultra-thin carbon nitride nanosheet-coated In2O3 (In2O3/CNS) S-type heterojunction-based PEC aptasensor has been established to achieve highly sensitive detection of diazinon (DZN) pesticide in water environment. Construction of S-type heterojunction induces a band shift and an electric field effect, enhancing light utilization and accelerating directional transmission of carriers, leading to outstanding PEC performance. The creation of internal electric field at interface ensures stable carrier transport. Additionally, ultrathin CNS structure can effectively shorten the transport path of carriers. The close coating of In2O3 and CNS promotes the transfer of charge. The synergistic effects amplify the sensor's response, ultimately enabling the effective detection of DZN residue over a wide detection range (0.98 âˆ¼ 980.0 pg mL-1), a low detection limit (0.33 pg mL-1, S/N = 3) and excellent accuracy in practical application (RSD < 5 %). This work provides a reference for the construction of a new S-type heterojunction-based PEC sensor.

A photoelectrochemical aptasensor based on W6+-doped carbon nitride with carbon-rich structure for sensitive detection of diazinon.

A photoelectrochemical (PEC) aptasensor us reported based on W6+-doped carbon nitride with carbon-rich structure (WCCN). WCCN exhibited excellent photoelectric conversion performance owing to the carbon-rich structure and W6+ doping. C atoms can replace the center N/edge N atoms to form a carbon-rich structure, improving the insufficient light absorption of CN in the visible region. Also, W6+ doping forms a directional electron transfer channel, achieving the efficient separation and transport of carriers. W6+ doping and carbon-rich structure can promote the generation, transfer, and separation of photogenerated carriers, further enhancing PEC performance. The fabricated PEC aptasensor based on WCCN demonstrated a wide detection range (3.92 ~ 588 pg L-1), a low detection limit (1.31 pg L-1, S/N = 3), good reproducibility, selectivity, stability, and practical application in actual water samples. This work explores the modification strategy of element doping for carbon nitride with high photoelectric property and offers a cost-effective and simplified method for the detection of pesticide residues.

[Effects of mild moxibustion on visceral hypersensitivity via SCF/c-kit signaling pathway in diarrhea-predominant irritable bowel syndrome rats with syndrome of liver-qi stagnation and spleen deficiency]. / åŸºäºŽå¹²ç»†èƒžç”Ÿé•¿å› å­/é ªæ°¨é ¸æ¿€é ¶å—ä½“ä¿¡å·é€šè·¯æŽ¢è®¨æ¸©å’Œç¸å¯¹è‚éƒè„¾è™šè¯è ¹æ³»åž‹è‚ æ˜“æ¿€ç»¼åˆå¾å¤§é¼ å† è„é«˜æ•æ„Ÿçš„å½±å“.

OBJECTIVES: To observe the effect of mild moxibustion on stem cell factor (SCF)/tyrosine kinase receptor (c-kit) signaling pathway and visceral hypersensitivity of diarrhea predominant irritable bowel syndrome (IBS-D) model rats with liver-qi stagnation and spleen deficiency syndrome, so as to explore its mechanisms underlying improvement of IBS-D. METHODS: A total of 24 male Wistar rats were randomly divided into normal, IBS-D model, medication and mild moxibustion groups, with 6 rats in each group. The IBS-D model was established by glacial acetic acid (4%) enema plus restraint stress stimulation once daily for 14 days. Rats of the medication group were treated by gavage of pivamium bromide (15 mg/kg) once a day for 14 days. Mild moxibustion was applied to bilateral "Tianshu"(ST25), "Shangjuxu"(ST37) and "Taichong"(LR3) for 20 min, once daily for 14 consecutive days. After the intervention, the rats' general state of each group were observed. The rate of loose stools (LSR), and the minimum volume threshold for abdominal withdrawal reflex(AWR) were observed, and the open field test was used to assess the state of rats' motor activities (including rearing times, grooming times and total number of square-crossings in 5 min). Morphological changes of the colon tissue were observed by hematoxylin-eosin (H.E.) staining, The count of mast cells (MC) in the colon tissues was determined by toluidine blue staining. Contents of serum 5-hydroxytryptamine (5-HT) and substance P (SP) were determined by enzyme-linked immunosorbent assay (ELISA). The relative expression levels of SCF and c-kit mRNAs and proteins in the colon tissues were detected by real-time quantitative PCR and Western blot, respectively. RESULTS: Compared with the normal group, the body weight, minimum volume threshold of AWR, total numbers of square-crossing, rearing times and grooming times were significantly decreased (P<0.05), and the LSR, number of MC, contents of 5-HT and SP, and the expression levels of SCF and c-kit mRNAs and proteins were considerably increased in the model group (P<0.01). In comparison with the model group after interventions, the body weight, minimum volume threshold of AWR, total numbers of square-crossing, rearing times and grooming times were apparently increased in both medication and moxibustion groups (P<0.05, P<0.01), and the LSR, number of MC, 5-HT and SP contents in both medication and moxibustion groups, and the expression levels of SCF and c-kit mRNA and protein in the moxibustion group (not in the medication group) were obviously decreased (P<0.05, P<0.01). H.E. staining showed that in the model group, a small amount of inflammatory cells in the mucosal layer of colon tissue could be seen. in the medication group, a small number of lymphocytes in colon tissue were observed, while in the mild moxibustion group, a small amount of neutrophils in colon tissue were observed. CONCLUSIONS: Mild moxibustion can reduce visceral hypersensitivity and improve abdominal pain, diarrhea and locomotion state in IBS-D rats with liver-qi stagnation and spleen deficiency syndrome, which may be associated with its functions in reducing the number of MC and the levels of 5-HT and SP and down-regulating the activities of SCF/c-kit signaling pathway.

Achieving ultra-low voltage fading in Co-free Li-rich layered oxides via effortless surface defect engineering.

Cobalt (Co)-free lithium (Li)-rich layered oxides (LLOs) have emerged as promising cathode materials for the next generation of Li-ion batteries, attributed to their competitive market positioning and high energy density. Nevertheless, challenges arise from surface oxygen loss due to irreversible anionic redox reactions, leading to severe voltage and capacity decay that hinder the large-scale adoption of LLOs. Herein, we present an innovative, facile, and environmentally friendly hydrothermal approach to induce surface reconstruction of Li1.2Mn0.6Ni0.2O2 material. A multifaceted combination involving the spinel phase, oxygen vacancies, and reduced manganese is orchestrated to alleviate the irreversible oxygen redox and impressively enhance Li-ion diffusion. The modified sample, owing to this surface transition, demonstrates low-strain and low-distortion properties along with a substantial improvement in structural stability, supported by both experimental validations and theoretical studies. As a result, the engineered sample exhibits exceptional capacity retention of 97.12% after 150 cycles at 1C, with an ultra-low voltage decay (0.91 mV cycle-1). Additionally, noteworthy enhancements in initial coulombic efficiency and rate performance are also observed. This straightforward surface defect engineering method offers a pathway to developing "low-strain" LLOs with superior electrochemical performance, thereby laying a solid foundation for future commercial applications.

Trinitarian Design of Gradient Artificial Interphase Enables Colossal Granular Li Deposits for Stable Li-Metal Batteries.

The cycling lifespan of Li-metal batteries is compromised by the unstable solid electrolyte interphase (SEI) and the continuous Li dendrites, restricting their practical implementations. Given these challenges, establishing an artificial SEI holds promise. Herein, a trinitarian gradient interphase is innovatively designed through composite coatings of magnesium fluoride (MgF2), N-hexadecyltrimethylammonium chloride (CTAC), and polyvinylidene fluoride-hexafluoropropylene copolymer (PVDF-HFP) on Li-metal anode (LMA). Specifically, the MgF2/CTAC/PVDF-HFP SEI spontaneously forms a lithium fluoride (LiF)-rich PVDF-HFP-based SEI, along with lithium-magnesium (Li-Mg) alloy substrate as lithiophilic electronic conductor and positively charged CTAC during plating. Noticeably, the Li-Mg alloy homogenizes the distribution of electric field and reduce the internal resistance, while the electronically insulated LiF/PVDF-HFP composite SEI offers fast ion-conducting and mechanical flexibility, accommodating the volumetric expansion and ensuring stable Li-ion flux. Additionally, CTAC at the dendritic tip is pivotal for mitigating dendrites through its electrostatic shield mechanism. Innovatively, this trinitarian synergistic mechanism, which facilitates colossal granular Li deposits, constructs a dendrite-free LMA, leading to stable cycling performances in practical Li||LFP, popular Li||NCM811, and promising Li||S full cells. This work demonstrates the design of multifunctional composite SEI for comprehensive Li protection, thereby inspiring further advancements in artificial SEI engineering for alkali-metal batteries.

The Combination of Gd-EOB-DTPA Enhanced T1 Mapping with Apparent Diffusion Coefficient could Improve the Diagnostic Efficacy of Hepatocellular Carcinoma Grading.

BACKGROUND: Accurately predicting the hepatocellular carcinoma (HCC) grade may facilitate the rational selection of treatment strategies. The diagnostic efficacy of the combination of Gadolinium ethoxybenzy diethylenetriamine pentaacetic (Gd-EOB-DTPA) enhancement T1 mapping and apparent diffusion coefficient (ADC) values in predicting HCC grade needs further validation. OBJECTIVES: This study aimed to assess the capacity of Gd-EOB-DTPA-enhanced T1 mapping and ADC values, both individually and in combination, to discriminate between different grades of HCC. MATERIALS AND METHODS: From July 2017 to February 2020, 96 patients (male, 83; mean age, 53.67 years; age range, 29-71 years) clinically diagnosed with HCC were included in the present study. All patients underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI, including T1 mapping sequence) before surgery or biopsy. All the patients were categorized into 3 groups according to the pathological results (including 24 cases of well-differentiated HCCs, 59 cases of moderately differentiated HCCs, 13 cases of and poorly differentiated HCCs). The mean Gd-EOB-DTPA enhanced T1 values (ΔT1=[(T1pre-T1post)/T1pre]×100%) and ADC values between different grading groups of HCC were calculated and compared. The area under the characteristics curve (AUC), the diagnostic threshold, sensitivity, and specificity of ΔT1 and ADC for differential diagnosis were analyzed. RESULTS: Mean ΔT1 was 58% for well-differentiated HCCs, 50% for moderately-differentiated HCCs, and 43% for poorly-differentiated HCCs. ΔT1 showed statistical differences between the groups (P<0.001). The mean ADC values of the 3 groups were 1.11×10-3 mm2/s, 0.91×10-3 mm2/s, and 0.80×10-3mm2/s, respectively. ADC showed statistical differences between the groups (P<0.001). In discriminating well- differentiated group from the moderately differentiated group, the AUC of ΔT1 was 0.751 (95% CI: 0.642, 0.859), the AUC of ADC was 0.782 (95% CI: 0.671, 0.894), the AUC of combined model was 0.811 (95% CI: 0.709, 0.914). In discriminating the poorly differentiated group from the moderately differentiated group, the AUC of ΔT1 was 0.768 (95% CI: 0.634, 0.902), the AUC of ADC was 0.754 (95% CI: 0.603, 0.904), and the AUC of the combined model was 0.841 (95% CI: 0.729, 0.953). CONCLUSION: Gd-EOB-DTPA enhanced T1 mapping, and ADC values have complementary effects on the sensitivity and specificity for identifying different HCC grades. A combined model of Gd-EOB-DTPA-enhanced MRI T1 mapping and ADC values could improve diagnostic performance for predicting HCC grades.

Multifunctional pH-responsive hydrogel dressings based on carboxymethyl chitosan: Synthesis, characterization fostering the wound healing.

Antibiotic abuse is increasing the present rate of drug-resistant bacterial wound infections, producing a significant healthcare burden globally. Herein, we prepared a pH-responsive CMCS/PVP/TA (CPT) multifunctional hydrogel dressing by embedding the natural plant extract TA as a nonantibiotic and cross-linking agent in carboxymethyl chitosan (CMCS) and polyvinylpyrrolidone (PVP) to prompt wound healing. The CPT hydrogel demonstrated excellent self-healing, self-adaptive, and adhesion properties to match different wound requirements. Importantly, this hydrogel showed pH sensitivity and exhibited good activity against resistant bacteria and antioxidant activity by releasing TA in case of bacterial infection (alkaline). Furthermore, the CPT hydrogel exhibited coagulant ability and could rapidly stop bleeding within 30 s. The biocompatible hydrogel effectively accelerated wound healing in a full-thickness skin defect model by thickening granulation tissue, increasing collagen deposition, vascular proliferation, and M2-type macrophage polarization. In conclusion, this study demonstrates that multifunctional CPT hydrogel offers a candidate material with potential applications for infected skin wound healing.

Damage-Tolerant and Self-Repairing Web-Like Borate Type Binder Enable Stable Operation of Efficient Si-Based Anodes.

Novel binder designs are shown to be fruitful in improving the electrochemical performance of silicon (Si)-based anodes. However, issues with mechanical damage from dramatic volume change and poor lithium-ion (Li+) diffusion kinetics in Si-based materials still need to be addressed. Herein, an aqueous self-repairing borate-type binder (SBG) with a web-like architecture and high ionic conductivity is designed for Si and SiO electrodes. The 3D web-like architecture of the SBG binder enables uniform stress distribution, while its self-repairing ability promotes effective stress dissipation and mechanical damage repair, thereby enhancing the damage tolerance of the electrode. The tetracoordinate boron ions ( - BO 4 - $ - {\mathrm{BO}}_4^ - $ ) in the SBG binder boosts the Li transportation kinetics of Si-based electrodes. Based on dynamic covalent and ionic conductive boronic ester bonds, the diverse requirements of the binder, including uniform stress distribution, self-repairing ability, and high ionic conductivity, can be met by simple components. Consequently, the proposed straightforward multifunction design strategy for binders based on dynamic boron chemistry provides valuable insights into fabricating high-performance Si-based anodes.

Construction of Dual-Active Sites by Interfacing with Polyhydroxy Fullerene on Nickel Hydroxide Surfaces to Promote CO2 Deep Photoreduction to CH4.

Due to the complex series of elementary steps involved, achieving deep photoreduction of CO2 to multielectron products such as CH4 remains a challenging task. Therefore, it is crucial to strategically design catalysts that facilitate the controlled formation of the crucial intermediates and provide precise control over the reaction pathway. Herein, we present a pioneering approach by employing polyhydroxy fullerene (PHF) molecules to modify the surface of Ni(OH)2, creating stable and effective synergistic sites to enhance the formation of CH4 from CO2 under light irradiation. As a result, the optimized PHF-modified Ni(OH)2 cocatalyst achieves a CH4 production rate of 455 µmol g-1 h-1, with an electron-based selectivity of approximately 60%. The combination of in situ characterizations and theoretical calculations reveals that the hydroxyl species on the surface of PHF can participate in stabilizing crucial intermediates and facilitating water activation, thereby altering the reaction pathway to form CH4 instead of CO. This study provides a novel approach to regulating the selectivity of photocatalytic CO2 reduction by exploring molecular surface modification through interfacing with functionalized carbon clusters.

A comprehensive review on targeting cluster of differentiation: An attractive strategy for inhibiting viruses through host proteins.

Viral infections continue to pose a significant global public health threat. Targeting host proteins, such as cluster of differentiation (CD) macromolecules, may offer a promising alternative approach to developing antiviral treatments. CDs are cell-surface biological macromolecules mainly expressed on leukocytes that viruses can use to enter cells, thereby evading immune detection and promoting their replication. The manipulation of CDs by viruses may represent an effective and clever means of survival through the prolonged co-evolution of hosts and viruses. Targeting of CDs is anticipated to hinder the invasion of related viruses, modulate the body's immune system, and diminish the incidence of subsequent inflammation. They have become crucial for biomedical diagnosis, and some have been used as valuable tools for resisting viral infections. However, a summary of the structures and functions of CDs involved in viral infection is currently lacking. The development of drugs targeting these biological macromolecules is restricted both in terms of their availability and the number of compounds currently identified. This review provides a comprehensive analysis of the critical role of CD proteins in virus invasion and a list of relevant targeted antiviral agents, which will serve as a valuable reference for future research in this field.

Electrolyte Design Chart Reframed by Intermolecular Interactions for High-Performance Li-Ion Batteries.

Developing advanced electrolytes has been regarded as a pivotal strategy for enhancing the electrochemical performance of batteries; however, the criteria for electrolyte design remain elusive. In this study, we present an electrolyte design chart reframed through intermolecular interactions. By combining systematic nuclear magnetic resonance, Fourier transform infrared measurements, molecular dynamics (MD) simulations, and machine-learning-assisted classifications, we establish semiquantitative correlations between electrolyte components and the electrochemical reversibility of electrolytes. We propose the equivalent increment of Li salt resulting from functional cosolvent and solvent-solvent interactions for effective electrolyte design and prediction. The controllable regulation of the electrolyte design chart by the properties of solvent-solvent interactions presents varying equivalent effects of increasing Li salt concentrations in different electrolyte systems. Based on this mechanism, we demonstrate highly reversible and nonflammable phosphate-based electrolytes for graphite||NCM811 full cells. The proposed electrolyte design chart, semiquantitatively determined by intermolecular interactions, provides the necessary experimental foundation and basis for the future rapid screening and prediction of electrolytes using machine-learning methods.

Anti-Coronavirus Potential of Polyether Ionophores: The New Application of Veterinary Antibiotics in Livestock.

Coronaviruses have consistently posed a major global concern in the field of livestock industry and public health. However, there is currently a lack of efficient drugs with broad-spectrum antiviral activity to address the challenges presented by emerging mutated strains or drug resistance. Additionally, the method for identifying multitarget drugs is also insufficient. Aminopeptidase N (APN) and 3C-like proteinase (3CLpro) represent promising targets for host-directed and virus-directed strategies, respectively, in the development of effective drugs against various coronaviruses. In this study, maduramycin ammonium demonstrated a broad-spectrum antiviral effect by targeting both of the proteins. The binding domains 4 Å from the ligand of both target proteins shared a structural similarity, suggesting that screening and designing drugs based on these domains might exhibit broad-spectrum and highly effective antiviral activity. Furthermore, it was identified that the polyether ionophores' ability to carry zinc ion might be one of the reasons why they were able to target APN and exhibit antiviral effect. The findings of this experiment provide novel perspectives for future drug screening and design, while also offering valuable references for the utilization of polyether ionophores in the management of livestock health.

Building and Validation of an Acute Event Prediction Model for Severe Mental Disorders.

Background: The global incidence of acute events in psychiatric patients is intensifying, and models to successfully predict acute events have attracted much attention. Objective: To explore the influence factors of acute incident severe mental disorders (SMDs) and the application of Rstudio statistical software, and build and verify a nomogram prediction model. Methods: SMDs were taken as research objects. The questionnaire survey method was adopted to collect data. Patients with acute event independent factors were screened. R software multivariable Logistic regression model was constructed and a nomogram was drawn. Results: A total of 342 patients with SMDs were hospitalized, and the number of patients who encountered acute events was 64, which accounted for 18.70% of all patients. Statistical significances were found in many aspects (all P ˂ 0.05). Such aspects included Medication adherence, disease diagnosis, marital status, caregivers, social support and the hospitalization environment (odds ratio (OR) = 4.08, 11.62, 12.06, 10.52, 0.04 and 0.61, respectively) were independent risk factors for the acute events of patients with SMDs. The prediction model was modeled, and the AUC was 0.77 and 0.80. The calibration curve shows that the model has good calibration. The clinical decision curve shows that the model has a good clinical effect. Conclusion: The constructed risk prediction model shows good prediction effectiveness in the acute events of patients with SMDs, which is helpful for the early detection of clinical mental health staff at high risk of acute events.

Comparative analysis of the intestinal flora of BmNPV-resistant and BmNPV-sensitive silkworm varieties.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a very common and infectious virus that affects silkworms and hinders silk production. To investigate the intestinal flora of BmNPV-resistant and BmNPV-sensitive silkworm varieties, 16 S rDNA high-throughput sequencing was performed. The results of the cluster analysis showed that the intestinal flora of the resistant silkworm variety was more abundant than that of the sensitive silkworm variety. This was found even when infection with BmNPV caused a sharp decline in the number of intestinal floral species in both resistant and sensitive silkworm varieties. The abundances of the intestinal flora, including Aureimonas, Ileibacterium, Peptostreptococcus, Pseudomonas, Enterococcus, and Halomonas, in the resistant variety were considerably greater after infection with BmNPV than those in the sensitive variety. After infection with BmNPV, four kinds of important intestinal bacteria, namely, f_Saccharimonadaceae, Peptostreptococcus, Aureirmonas, and f_Rhizobiaceae, were found in the resistant silkworm variety. In the sensitive silkworm variety, only Faecalibaculum was an important intestinal bacterium. The differential or important bacteria mentioned above might be involved in immunoreaction or antiviral activities, especially in the intestines of BmNPV-resistant silkworms. By conducting a functional enrichment analysis, we found that BmNPV infection did not change the abundance of important functional components of the intestinal flora in resistant or sensitive silkworm varieties. However, some functional factors, such as the biosynthesis, transport, and catabolism of secondary metabolites (e.g., terpenoids and polyketides) and lipid transport and metabolism, were more important in the resistant silkworm variety than in the sensitive variety; thus, these factors may increase the resistance of the host to BmNPV. To summarize, we found significant differences in the composition, abundance, and function of the intestinal flora between resistant and sensitive silkworm varieties, especially after infection with BmNPV, which might be closely related to the resistance of resistant silkworm varieties to BmNPV.

Identification of PTPN12 Phosphatase as a Novel Negative Regulator of Hippo Pathway Effectors YAP/TAZ in Breast Cancer.

The Hippo pathway plays crucial roles in governing various biological processes during tumorigenesis and metastasis. Within this pathway, upstream signaling stimuli activate a core kinase cascade, involving MST1/2 and LATS1/2, that subsequently phosphorylates and inhibits the transcriptional co-activators YAP and its paralog TAZ. This inhibition modulates the transcriptional regulation of downstream target genes, impacting cell proliferation, migration, and death. Despite the acknowledged significance of protein kinases in the Hippo pathway, the regulatory influence of protein phosphatases remains largely unexplored. In this study, we conducted the first gain-of-functional screen for protein tyrosine phosphatases (PTPs) regulating the Hippo pathway. Utilizing a LATS kinase biosensor (LATS-BS), a YAP/TAZ activity reporter (STBS-Luc), and a comprehensive PTP library, we identified numerous novel PTPs that play regulatory roles in the Hippo pathway. Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer biology and potential therapeutic strategies.

Advances in sarcopenia: mechanisms, therapeutic targets, and intervention strategies.

Sarcopenia is a multifactorial condition characterized by loss of muscle mass. It poses significant health risks in older adults worldwide. Both pharmacological and non-pharmacological approaches are reported to address this disease. Certain dietary patterns, such as adequate energy intake and essential amino acids, have shown positive outcomes in preserving muscle function. Various medications, including myostatin inhibitors, growth hormones, and activin type II receptor inhibitors, have been evaluated for their effectiveness in managing sarcopenia. However, it is important to consider the variable efficacy and potential side effects associated with these treatments. There are currently no drugs approved by the Food and Drug Administration for sarcopenia. The ongoing research aims to develop more effective strategies in the future. Our review of research on disease mechanisms and drug development will be a valuable contribution to future research endeavors.

Design and synthesis of APN and 3CLpro dual-target inhibitors based on STSBPT with anticoronavirus activity.

Coronaviruses (CoVs) have continuously posed a threat to human and animal health. However, existing antiviral drugs are still insufficient in overcoming the challenges caused by multiple strains of CoVs. And methods for developing multi-target drugs are limited in terms of exploring drug targets with similar functions or structures. In this study, four rounds of structural design and modification on salinomycin were performed for novel antiviral compounds. It was based on the strategy of similar topological structure binding properties of protein targets (STSBPT), resulting in the high-efficient synthesis of the optimal compound M1, which could bind to aminopeptidase N and 3C-like protease from hosts and viruses, respectively, and exhibit a broad-spectrum antiviral effect against severe acute respiratory syndrome CoV 2 pseudovirus, porcine epidemic diarrhea virus, transmissible gastroenteritis virus, feline infectious peritonitis virus and mouse hepatitis virus. Furthermore, the drug-binding domains of these proteins were found to be structurally similar based on the STSBPT strategy. The compounds screened and designed based on this region were expected to have broad-spectrum and strong antiviral activities. The STSBPT strategy is expected to be a fundamental tool in accelerating the discovery of multiple targets with similar effects and drugs.

Bi-Directional H-Bonding Modulated Soft/Hard Polyethylene Glycol-Polyaniline Coated Si-Anode for High-Performance Li-Ion Batteries.

Ultrahigh-capacity silicon (Si) anodes are essential for the escalating energy demands driven by the booming e-transportation and energy storage field. However, their practical applications are strictly hampered by their intrinsically low electroconductivity, sluggish Li-ion diffusion, and undesirably large volume change. Herein, a high-performance Si anode, comprised of a modulated soft/hard coating of polyethylene glycol (PEG) (as Li-ion conductor) and polyaniline (PANI) (as electron conductor) on the surface of Si nanoparticles (NPs) through H-bonding network, is introduced. In this design, the abundant ─OH groups of soft PEG allow it to uniformly cover Si NPs while the hard PANI binds to PEG through its ─N─H group, thus constructing a tight connectin between Si and PEG-PANI (PP). Consequently, the elastic PP allows Si@PP to accommodate the huge volume expansion while possessing fine electronic/ionic conductivity. Therefore, the Si@PP anode exhibits a high initial Coulombic efficiency of 90.5% and a stable capacity of 1871 mAh g-1 after 100 cycles at 1 A g-1 with a retention of 85.7%. Additionally, the Si@PP anode also demonstrates a high areal capacity of 3.01 mAh cm-2 after 100 cycles at 0.5 A g-1. This work reveals a scalable interface design of multi-layer multifunctional coatings for high-performance electrode materials in next-generation Li-ion batteries.

Flexiplex: a versatile demultiplexer and search tool for omics data.

MOTIVATION: The process of analyzing high throughput sequencing data often requires the identification and extraction of specific target sequences. This could include tasks, such as identifying cellular barcodes and UMIs in single-cell data, and specific genetic variants for genotyping. However, existing tools, which perform these functions are often task-specific, such as only demultiplexing barcodes for a dedicated type of experiment, or are not tolerant to noise in the sequencing data. RESULTS: To overcome these limitations, we developed Flexiplex, a versatile and fast sequence searching and demultiplexing tool for omics data, which is based on the Levenshtein distance and thus allows imperfect matches. We demonstrate Flexiplex's application on three use cases, identifying cell-line-specific sequences in Illumina short-read single-cell data, and discovering and demultiplexing cellular barcodes from noisy long-read single-cell RNA-seq data. We show that Flexiplex achieves an excellent balance of accuracy and computational efficiency compared to leading task-specific tools. AVAILABILITY AND IMPLEMENTATION: Flexiplex is available at https://davidsongroup.github.io/flexiplex/.

STAT5 is essential for inducing the suppressive subset and attenuate cytotoxicity of Vδ2+ T cells in acute myeloid leukemia.

Under the sustained exposure to tumor microenvironment, effector lymphocytes may transform into the suppressive populations. γδ T cells are recognized as a crucial mediator and effector of immune surveillance and thereby a promising candidate for anti-tumor immunotherapy. Emerging clinical studies implicate that some γδ T subsets play an important role in promoting tumor progression. Our previous study identified an abnormal Vδ2+ T cells subset with regulatory features (Reg-Vδ2) in the patients with newly diagnosed acute myeloid leukemia (AML), and demonstrated that Reg-Vδ2 cells significantly suppressed the anti-AML effects of effector Vδ2 cells (Eff-Vδ2). The molecular mechanism underlying the subset transformation of Vδ2 cells remains unclear. Here, we found that the expression and activity of STAT5 were significantly induced in Reg-Vδ2 cells compared with Eff-Vδ2 cells, which was consistent with the differences found in primary Vδ2 cells between AML patients and healthy donors. In-vitro experiments further indicated that STAT5 was required for the induction of Reg-Vδ2 cells. The combined immunophenotypical and functional assays showed that blockage of STAT5 alleviated the immunosuppressive effect of Reg-Vδ2 cells on Eff-Vδ2 cells and enhanced the anti-AML capacity of Vδ2 cells from health donors and AML patients. Collectively, these results suggest that STAT5 acts as a critical regulator in the transformation of effector Vδ2 cells into a subset with immunosuppressive characteristics, providing a potential target for the improvement the efficacy of γδ T cells-based immunotherapy to treat AML and other hematologic malignancies.