Spontaneous single-nucleotide substitutions and microsatellite mutations have distinct distributions of fitness effects.

The fitness effects of new mutations determine key properties of evolutionary processes. Beneficial mutations drive evolution, yet selection is also shaped by the frequency of small-effect deleterious mutations, whose combined effect can burden otherwise adaptive lineages and alter evolutionary trajectories and outcomes in clonally evolving organisms such as viruses, microbes, and tumors. The small effect sizes of these important mutations have made accurate measurements of their rates difficult. In microbes, assessing the effect of mutations on growth can be especially instructive, as this complex phenotype is closely linked to fitness in clonally evolving organisms. Here, we perform high-throughput time-lapse microscopy on cells from mutation-accumulation strains to precisely infer the distribution of mutational effects on growth rate in the budding yeast, Saccharomyces cerevisiae. We show that mutational effects on growth rate are overwhelmingly negative, highly skewed towards very small effect sizes, and frequent enough to suggest that deleterious hitchhikers may impose a significant burden on evolving lineages. By using lines that accumulated mutations in either wild-type or slippage repair-defective backgrounds, we further disentangle the effects of 2 common types of mutations, single-nucleotide substitutions and simple sequence repeat indels, and show that they have distinct effects on yeast growth rate. Although the average effect of a simple sequence repeat mutation is very small (approximately 0.3%), many do alter growth rate, implying that this class of frequent mutations has an important evolutionary impact.

ERK inhibition rescues defects in fate specification of Nf1-deficient neural progenitors and brain abnormalities.

Germline mutations in the RAS/ERK signaling pathway underlie several related developmental disorders collectively termed neuro-cardio-facial-cutaneous (NCFC) syndromes. NCFC patients manifest varying degrees of cognitive impairment, but the developmental basis of their brain abnormalities remains largely unknown. Neurofibromatosis type 1 (NF1), an NCFC syndrome, is caused by loss-of-function heterozygous mutations in the NF1 gene, which encodes neurofibromin, a RAS GTPase-activating protein. Here, we show that biallelic Nf1 inactivation promotes Erk-dependent, ectopic Olig2 expression specifically in transit-amplifying progenitors, leading to increased gliogenesis at the expense of neurogenesis in neonatal and adult subventricular zone (SVZ). Nf1-deficient brains exhibit enlarged corpus callosum, a structural defect linked to severe learning deficits in NF1 patients. Strikingly, these NF1-associated developmental defects are rescued by transient treatment with an MEK/ERK inhibitor during neonatal stages. This study reveals a critical role for Nf1 in maintaining postnatal SVZ-derived neurogenesis and identifies a potential therapeutic window for treating NF1-associated brain abnormalities.

Emergence of silent NDM-1 carbapenemase gene in carbapenem-susceptible Klebsiella pneumoniae: Clinical implications and epidemiological insights.

The global dissemination of carbapenemase genes, particularly blaNDM-1, poses a significant threat to public health. While research has mainly focused on strains with phenotypic resistance, the impact of silent resistance genes has been largely overlooked. This study documents the first instance of silent blaNDM-1 in a cluster of clonally related carbapenem-susceptible K. pneumoniae strains from a single patient. Despite initial effectiveness of carbapenem therapy, the patient experienced four recurrent lung infections over five months, indicating persistent K. pneumoniae infection. Genomic sequencing revealed all strains harbored blaNDM-1 on the epidemic IncX3 plasmid. A deletion within the upstream promoter region (PISAba125) of blaNDM-1 hindered its expression, resulting in phenotypic susceptibility to carbapenems. However, in vitro bactericidal assays and a mouse infection model showed that K. pneumoniae strains with silent blaNDM-1 exhibited significant tolerance to carbapenem-mediated killing. These findings demonstrate that silent blaNDM-1 can mediate both phenotypic susceptibility and antibiotic tolerance. In silico analysis of 1986 blaNDM sequences showed that 1956 (98.5%) retained the original promoter PISAba125. Given that previous genomic sequencing typically targets carbapenem-resistant strains, accurately assessing the prevalence of silent blaNDM remains challenging. This study highlights the hidden threat of silent resistance genes to clinical antimicrobial therapy and calls for enhanced clinical awareness and laboratory detection.

Profound primary prevention of liver cancer following a natural experiment in China: A 50-year perspective and public health implications.

Liver cancer causes upwards of 1 million cancer deaths annually and is projected to rise by at least 55% over the next 15 years. Two of the major risk factors contributing to liver cancer have been well documented by multiple epidemiologic studies and the hepatitis B virus (HBV) and aflatoxin show a synergy that increases by more than 8-fold the risk of liver cancer relative to HBV alone. Using the population-based cancer registry established by the Qidong Liver Cancer Institute in 1972 and aflatoxin-specific biomarkers, we document that reduction of aflatoxin exposure has likely contributed to a nearly 70% decline in age-standardized liver cancer incidence over the past 30 years despite an unchanging prevalence of HBV infection in cases. A natural experiment of economic reform in the 1980s drove a rapid switch from consumption of heavily contaminated corn to minimally, if any, contaminated rice and subsequent dietary diversity. Aflatoxin consumption appears to accelerate the time to liver cancer diagnosis; lowering exposure to this carcinogen adds years of life before a cancer diagnosis. Thus, in 1990 the median age of diagnosis was 48 years, while increasing to 67 years by 2021. These findings have important translational public health implications since up to 5 billion people worldwide might be routinely exposed to dietary aflatoxin, especially in societies using corn as the staple food. Interventions against aflatoxin are an achievable outcome leading to a reduction in liver cancer incidence and years of delay of its nearly always fatal diagnosis.

LINC00629, a HOXB4-downregulated long noncoding RNA, inhibits glycolysis and ovarian cancer progression by destabilizing c-Myc.

Ovarian cancer (OC) cells typically reprogram their metabolism to promote rapid proliferation. However, the role of long noncoding RNAs (lncRNAs) in the metabolic reprogramming of ovarian cancer, especially in glucose metabolic reprogramming, remains largely unknown. LINC00629 has been reported in our previous study to promote osteosarcoma progression. Upregulated LINC00629 was found to enhance the growth-suppressive effect of apigenin on oral squamous cell carcinoma. However, the precise function of LINC00629 in ovarian cancer development remains poorly understood. In this study, we found that LINC00629 was significantly downregulated in OC tissues and that low LINC00629 expression was associated with poor survival. Inhibition of LINC00629 was required for increased glycolysis activity and cell proliferation in ovarian cancer. In vivo, overexpression of LINC00629 dramatically inhibited tumor growth and lung metastasis. Mechanistically, LINC00629 interacted with and destabilized c-Myc, leading to its ubiquitination and proteasome degradation, further resulting in increased expression of downstream glycolysis-related genes and glucose metabolic reprogramming in OC. Interestingly, HOXB4 bound to the LINC00629 promoter and inhibited its transcription, indicating that LINC00629 is a transcriptional target of HOXB4. Collectively, these findings establish a direct role for LINC00629 in suppressing glucose metabolism, and HOXB4/LINC00629/c-Myc might serve as a potential biomarker and an effective therapeutic strategy for OC cancer treatment.

Dual Engine Boosts Organic Photoelectrochemical Transistor for Enhanced Modulation and Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.

Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

scDEA: differential expression analysis in single-cell RNA-sequencing data via ensemble learning.

The identification of differentially expressed genes between different cell groups is a crucial step in analyzing single-cell RNA-sequencing (scRNA-seq) data. Even though various differential expression analysis methods for scRNA-seq data have been proposed based on different model assumptions and strategies recently, the differentially expressed genes identified by them are quite different from each other, and the performances of them depend on the underlying data structures. In this paper, we propose a new ensemble learning-based differential expression analysis method, scDEA, to produce a more stable and accurate result. scDEA integrates the P-values obtained from 12 individual differential expression analysis methods for each gene using a P-value combination method. Comprehensive experiments show that scDEA outperforms the state-of-the-art individual methods with different experimental settings and evaluation metrics. We expect that scDEA will serve a wide range of users, including biologists, bioinformaticians and data scientists, who need to detect differentially expressed genes in scRNA-seq data.

Ultrahigh-Precision Hamiltonian Parameter Estimation in a Superconducting Circuit.

The Hamiltonian, which determines the evolution of a quantum system, is fundamental in quantum physics. Therefore, it is crucial to implement high-precision generation and measurement of the Hamiltonian in a practical quantum system. Here, we experimentally demonstrate ultrahigh-precision Hamiltonian parameter estimation with a significant quantum advantage in a superconducting circuit via sequential control. We first observe the commutation relation for noncommuting operations determined by the system Hamiltonian, both with and without adding quantum control, verifying the commuting property of controlled noncommuting operations. Based on this control-induced commuting property, we further demonstrate Hamiltonian parameter estimation for polar and azimuth angles in superconducting circuits, achieving ultrahigh metrological gains in measurement precision exceeding the standard quantum limit by up to 16.0 and 16.1 dB at N=100, respectively.

Heterogeneous Porous Synergistic Photocatalysts for Organic Transformations.

Recent interest has surged in using heterogeneous carriers to boost synergistic photocatalysis for organic transformations. Heterogeneous catalysts not only facilitate synergistic enhancement of distinct catalytic centers compared to their homogeneous counterparts, but also allow for the easy recovery and reuse of catalysts. This mini-review summarizes recent advancements in developing heterogeneous carriers, including metal-organic frameworks, covalent-organic frameworks, porous organic polymers, and others, for synergistic catalytic reactions. The advantages of porous materials in heterogeneous catalysis originate from their ability to provide a high surface area, facilitate enhanced mass transport, offer a tunable chemical structure, ensure the stability of active species, and enable easy recovery and reuse of catalysts. Both photosensitizers and catalysts can be intricately incorporated into suitable porous carriers to create heterogeneous dual photocatalysts for organic transformations. Notably, experimental evidence from reported cases has shown that the catalytic efficacy of heterogeneous catalysts often surpasses that of their homogeneous analogues. This enhanced performance is attributed to the proximity and confinement effects provided by the porous nature of the carriers. It is expected that porous carriers will provide a versatile platform for integrating diverse catalysts, thus exhibiting superior performance across a range of organic transformations and appealing prospect for industrial applications.

Activation of moderate autophagy promotes survival of fat graft.

Clinically unpredictable retention following fat grafting remains outstanding problems because of the unrevealed mechanism of grafted fat survival. The role of autophagy, a process to maintain cellular homeostasis through recycling cellular debris, has yet been to be reported in fat grafting. This study aims to improve the survival of fat grafting through the autophagy. First, the relationship between cell death and autophagy in the early stage of fat grafting was evaluated through immunostaining, RNA sequencing, and western blot. Next, rapamycin, an autophagic agonist, was used for the culturing of adipose-derived stem cells and adipocytes during ischemia. Cell death, autophagy, and reactive oxygen species (ROS) were assayed. Finally, rapamycin was used to assist fat grafting in nude mice. The results demonstrated that the peak of cell death at the early stage of fat grafting was accompanied by a decrease in autophagy. In vitro, during ischemia, 25 nM was confirmed as the optimal dose of rapamycin that reduces cell death with enhanced autophagy and mitophagy, improved mitochondrial quality as well as decreased ROS accumulation. In vivo, promoted mitophagy, alleviated oxidative stress, and decreased cell apoptosis of rapamycin-treated fat grafts were observed in the early stage. In addition, rapamycin increased the survival of fat grafts with increased neovascularization and reduced fibrosis. We suggested that moderate autophagy induced by rapamycin contribute to enhanced ischemic tolerance and long term survival of fat grafts through mitochondrial quality control.

The Association of Systemic Inflammatory Response Index and Neutrophil-to-High-Density Lipoprotein Ratio Mediated by Fasting Blood Glucose with 90-Day Prognosis in Acute Ischemic Stroke Patients.

INTRODUCTION: The contribution of individual and combined inflammatory markers for the prognosis of acute ischemic stroke (AIS) remains elusive. This study investigated the effect of systemic inflammatory response index (SIRI), and neutrophil to high-density lipoprotein ratio (NHR), which is mediated by fasting blood glucose (FBG), on 90-day prognosis of patients with AIS. METHODS: In this pre-specified substudy of an observational cohort study, 2,828 patients with AIS were enrolled from the Nanjing Stroke Registry between January 2017 and July 2021. Peripheral venous blood was collected from patients fasting for at least 8 h within 24 h of admission to gather information on the following parameters: neutrophil count, lymphocyte count, monocyte count, HDL level, and fasting blood glucose level. Then, the SIRI and NHR values were calculated. Following this, the correlation among SIRI, NHR, and modified Rankin Scale (mRS) scores 90 days after onset was examined via univariate and multivariate logistic analyses. Lastly, mediation analysis was performed to examine the relationship between systematic inflammatory response and study outcomes mediated by FBG. RESULTS: SIRI and NHR were both negatively correlated with clinical outcomes (p < 0.05). Logistic regression analysis revealed that SIRI and NHR were independently associated with poor outcomes after adjusting for potential confounders. Subgroup analyses further validated these correlations. Meanwhile, mediation analysis corroborated that FBG partially mediated the associations between SIRI and a poor prognosis at 90 days (indirect effect estimate = 0.0038, bootstrap 95% CI 0.001-0.008; direct effect estimate = 0.1719, bootstrap 95% CI 0.1258-0.2179). Besides, FBG also played a mediating role between NHR and poor outcomes (indirect effect estimate = 0.0066, bootstrap 95% CI 0.002-0.120; direct effect estimate = 0.1308, bootstrap 95% CI 0.0934-0.1681). CONCLUSION: Our study demonstrated that SIRI and NHR are positively associated with poor clinical and mortality outcomes at 90 days in AIS patients, which was partially mediated by FBG.

Effect of different nutrients on blood glucose, inflammatory response and oxidative stress in gestational diabetes mellitus: a network meta-analysis.

We searched PubMed, Web of Science, Embase, The Cochrane Library, China Biomedical Literature Database and other databases from inception to June 2023. The included studies were randomised controlled trials (RCT). The studies were screened by four authors, divided into two independent pairs. A total of eighteen studies were included, including 1362 patients, involving twelve intervention measures. The different nutrients had a significant effect on improving blood glucose, reducing inflammation levels and reducing oxidative stress compared with placebo (P < 0.05). Cumulative probability ranking showed that vitamin A + vitamin D + vitamin E ranked first in lowering fasting blood glucose (standardised mean difference (SMD) = 41.30, 95 % CI (2.07, 825.60)) and postprandial 2-h blood glucose (SMD = 15.19, 95 % CI (4.16, 55.53)). In terms of insulin resistance index, the first highest probability ranking is vitamin D (SMD = 5.12, 95 % CI (0.76, 34.54)). In terms of reducing the high-sensitivity C-reactive protein level, the first in probability ranking is VE (SMD = 2.58, 95 % CI (1.87,3.55)). The results of cumulative probability ranking showed that Mg + Zn + Ca + VD ranked first in reducing TNF-α (SMD = 1.90, 95% CI (0.40, 9.08)) and IL-6 (SMD = 1.83, 95 % CI (0.37, 9.12)). In terms of reducing malondialdehyde levels, the first ranked probability is VB1 (SMD = 4.99, 95 % CI (1.85, 13.46)). Cumulative probability ranking results showed that Ca + VD ranked first in reducing total antioxidant capacity (SMD = 0.66,95 % CI (0.38, 1.15)) and glutathione (SMD = 1.39, 95 % CI (0.43, 4.56)). In conclusion, nutritional interventions have significant effects on improving blood glucose, inflammatory levels and oxidative stress in patients with gestational diabetes. Due to the high uncertainty in the results and differences in the number and quality of studies included, the reliability of the conclusions still needs to be validated by conducting large-sample, high-quality RCT studies.

Evidence of Pericyte Damage in a Cognitively Normal Cohort: Association With CSF and PET Biomarkers of Alzheimer Disease.

BACKGROUND: Blood-brain barrier (BBB) dysfunction is emerging as an important pathophysiologic factor in Alzheimer disease (AD). Cerebrospinal fluid (CSF) platelet-derived growth factor receptor-ß (PDGFRß) is a biomarker of BBB pericyte injury and has been implicated in cognitive impairment and AD. METHODS: We aimed to study CSF PDGFRß protein levels, along with CSF biomarkers of brain amyloidosis and tau pathology in a well-characterized population of cognitively unimpaired individuals and correlated CSF findings with amyloid-PET positivity. We performed an institutional review board (IRB)-approved cross-sectional analysis of a prospectively enrolled cohort of 36 cognitively normal volunteers with available CSF, Pittsburgh compound B PET/CT, Mini-Mental State Exam score, Global Deterioration Scale, and known apolipoprotein E ( APOE ) ε4 status. RESULTS: Thirty-six subjects were included. Mean age was 63.3 years; 31 of 36 were female, 6 of 36 were amyloid-PET-positive and 12 of 36 were APOE ε4 carriers. We found a moderate positive correlation between CSF PDGFRß and both total Tau (r=0.45, P =0.006) and phosphorylated Tau 181 (r=0.51, P =0.002). CSF PDGFRß levels were not associated with either the CSF Aß42 or the amyloid-PET. CONCLUSIONS: We demonstrated a moderate positive correlation between PDGFRß and both total Tau and phosphorylated Tau 181 in cognitively normal individuals. Our data support the hypothesis that BBB dysfunction represents an important early pathophysiologic step in AD, warranting larger prospective studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00094939.

Study of resistive switching behavior in HfO2nanocrystals synthesized via a low temperature hydrothermal method.

The resistive switching property in HfO2have attracted increasing interest in recent years. In this work, amorphous HfO2nanocrystals are synthesized by a facile hydrothermal method. Then, the as-synthesized nanocrystals are rapid thermal annealed in different atmospheres for improving the crystal quality, and monoclinic phase is determined as the main crystal structure of the annealed HfO2. Subsequently, metal-insulator-metal structure devices based on HfO2samples are fabricated. Electrical measurement indicates that 700 °C annealing processes in Air and Ar environments can slightly improve the bipolar resistive switching and retention behaviors. Higher annealed temperature (900 °C) will further improve the crystal quality of HfO2, while the resistive switching and retention behaviors of the devices continuously attenuate, which can be ascribed to the reduction of the conductive filaments induced by defects.

Predicting latent lncRNA and cancer metastatic event associations via variational graph auto-encoder.

Long non-coding RNA (lncRNA) are shown to be closely associated with cancer metastatic events (CME, e.g., cancer cell invasion, intravasation, extravasation, proliferation) that collaboratively accelerate malignant cancer spread and cause high mortality rate in patients. Clinical trials may accurately uncover the relationships between lncRNAs and CMEs; however, it is time-consuming and expensive. With the accumulation of data, there is an urgent need to find efficient ways to identify these relationships. Herein, a graph embedding representation-based predictor (VGEA-LCME) for exploring latent lncRNA-CME associations is introduced. In VGEA-LCME, a heterogeneous combined network is constructed by integrating similarity and linkage matrix that can maintain internal and external characteristics of networks, and a variational graph auto-encoder serves as a feature generator to represent arbitrary lncRNA and CME pair. The final robustness predicted result is obtained by ensemble classifier strategy via cross-validation. Experimental comparisons and literature verification show better remarkable performance of VGEA-LCME, although the similarities between CMEs are challenging to calculate. In addition, VGEA-LCME can further identify organ-specific CMEs. To the best of our knowledge, this is the first computational attempt to discover the potential relationships between lncRNAs and CMEs. It may provide support and new insight for guiding experimental research of metastatic cancers. The source code and data are available at https://github.com/zhuyuan-cug/VGAE-LCME.

Rapamycin protects mouse skin from ultraviolet B-induced photodamage by modulating Hspb2-mediated autophagy and apoptosis.

BACKGROUND: Continuous exposure to UVB is the main extrinsic cause of skin photodamage, which is associated with oxidative stress, DNA damage, apoptosis and degradation of collagen. Rapamycin, a mechanistic target inhibitor of rapamycin complex 1 (mTORC1), has been shown to play a crucial role anti-tumor and aging retardation, but its mechanism of action in UVB-induced photodamage still remains unknown. In this study, we investigated the role of rapamycin and Hspb2 (also known as Hsp27) in UVB-induced photodamage in mice. METHODS AND RESULTS: We constructed skin acute photodamage models on the ears of WT and Hspb2 KO mice, respectively, and administered rapamycin treatment. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels, with a significant increase in p53 levels and Bax/Bcl-2 ratio, a reduction in LC3II/I ratio and an increase in p62 levels in the KO mice compared to those in WT mice after the same dose of UVB irradiation. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. CONCLUSIONS: Rapamycin can alleviate skin photodamage from Hspb2 knockout to some extent. It may be a potential therapeutic drug for skin photodamage. In this study, we investigated the role of rapamycin and Hspb2 in UVB-induced photodamage in mice. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. We conclude that rapamycin and Hspb2 exert a synergistic protective effect in skin photodamage.

Fabrication of PHFPO Surface-Modified Conductive AgNWs/PNAGA Hydrogels with Enhanced Water Retention Capacity toward Highly Sensitive Strain Sensors.

Conductive hydrogels, characterized by their unique features of flexibility, biocompatibility, electrical conductivity, and responsiveness to environmental stimuli, have emerged as promising materials for sensitive strain sensors. In this study, a facile strategy to prepare highly conductive hydrogels is reported. Through rational structural and synthetic design, silver nanowires (AgNWs) are incorporated into poly(N-acryloyl glycinamide) (PNAGA) hydrogels, achieving high electrical conductivity (up to 0.88 S m-1), significantly enhanced mechanical properties, and elevated deformative sensitivity. Furthermore, surface modification with polyhexafluoropropylene oxide (PHFPO) has substantially improved the water retention capacity and dressing comfort of this hydrogel material. Based on the above merits, these hydrogels are employed to fabricate highly sensitive wearable strain sensors which can detect and interpret subtle hand and finger movements and enable precise control of machine interfaces. The AgNWs/PNAGA based strain sensors can effectively sense finger motion, enabling the control of robotic fingers to replicate the human hand's gestures. In addition, the high deformative sensitivity and elevated water retention performance of the hydrogels makes them suitable for flow sensing. These conceptual applications demonstrate the potential of this conductive hydrogel in high-performance strain sensors in the future.

Zinc-doped C4N3/BiOBr S-scheme heterostructured hollow spheres for efficient photocatalytic degradation of tetracycline.

Photocatalytic degradation of organic pollutants in water is of great significance to the sustainable development of the environment, but encounters limited efficiency when a single compound is used. Thus, there have been enormous efforts to find novel photocatalytic heterostructured composites with high performance. In this work, a novel S-scheme heterostructure is constructed with BiOBr and Zn2+ doped C4N3 (Zn-C4N3) by a solvothermal method for efficient photodegradation of tetracycline (TC), a residual antibiotic difficult to be removed from the aquatic environment. Thanks to Zn2+-doping induced improvement in chemical affinity between Zn-C4N3 and BiOBr, well-formed Zn-C4N3/BiOBr heterostructured hollow spheres are formed. This structure can efficiently suppress fast recombination of photogenerated electron-hole pairs to enhance the photocatalytic activity of BiOBr dramatically. At a room temperature of 25 °C and neutral pH 7, the catalyst can degrade a significant portion of TC pollutants within 30 min under visible light. Also, the Zn-C4N3/BiOBr heterostructure displays good stability after recycling experiments. Free radical capture experiments and ESR tests show that ˙O2- is the main active substance for photocatalytic degradation of TC. This study provides new insights for constructing heterostructures with an intimate interface between the two phases for photocatalytic applications.

Non-peptidic inhibitors targeting SARS-CoV-2 main protease: A review.

The COVID-19 pandemic continues to pose a threat to global health, and sounds the alarm for research & development of effective anti-coronavirus drugs, which are crucial for the patients and urgently needed for the current epidemic and future crisis. The main protease (Mpro) stands as an essential enzyme in the maturation process of SARS-CoV-2, playing an irreplaceable role in regulating viral RNA replication and transcription. It has emerged as an ideal target for developing antiviral agents against SARS-CoV-2 due to its high conservation and the absence of homologous proteases in the human body. Among the SARS-CoV-2 Mpro inhibitors, non-peptidic compounds hold promising prospects owing to their excellent antiviral activity and improved metabolic stability. In this review, we offer an overview of research progress concerning non-peptidic SARS-CoV-2 Mpro inhibitors since 2020. The efforts delved into molecular structures, structure-activity relationships (SARs), biological activity, and binding modes of these inhibitors with Mpro. This review aims to provide valuable clues and insights for the development of anti-SARS-CoV-2 agents as well as broad-spectrum coronavirus Mpro inhibitors.