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The Ebola filovirus (EBOV) poses a serious threat to global health and national security. Nanobodies, a type of single-domain antibody, have demonstrated promising therapeutic potential. We identified two anti-EBOV nanobodies, Nanosota-EB1 and Nanosota-EB2, which specifically target the EBOV glycoprotein (GP). Cryo-EM and biochemical data revealed that Nanosota-EB1 binds to the glycan cap of GP1, preventing its protease cleavage, while Nanosota-EB2 binds to critical membrane-fusion elements in GP2, stabilizing it in the pre-fusion state. Nanosota-EB2 is a potent neutralizer of EBOV infection in vitro and offers excellent protection in a mouse model of EBOV challenge, while Nanosota-EB1 provides moderate neutralization and protection. Nanosota-EB1 and Nanosota-EB2 are the first nanobodies shown to inhibit authentic EBOV. Combined with our newly developed structure-guided in vitro evolution approach, they lay the foundation for nanobody-based therapies against EBOV and other viruses within the ebolavirus genus.

Fleas frequently parasitize rodents and serve as major vectors for many zoonotic diseases. The Alxa Desert in Inner Mongolia, China, is a typical arid region in Asia, which is suitable for the coexistence of a variety of rodents in this environment. Understanding the host selection of fleas among these rodents and the factors influencing this selection is crucial for comprehending rodent-borne diseases and the vector roles of fleas. This study utilized live-trap methods to capture rodents coexisting in the Alxa Desert from April to October 2022. Body surface fleas were collected and analyzed for abundance across different hosts, sexes, and reproductive statuses. The results indicated that: (1) there were significant differences in the species and abundance of parasitic fleas on different rodent species, with Ophthalmopsylla kiritschenkoi and Mesopsylla hebes preferring the Dipus sagitta and Orientallactaga sibirica as their hosts, and Xenopsylla conformis preferring Meriones meridianus as its host. (2) Fleas exhibited sex-preferential host selection, showing a greater preference for male hosts. (3) Among rodents of different reproductive states, most fleas prefer to parasitize individuals in non-reproductive periods. (4) The mean abundance of fleas varied significantly between seasons (P

Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic viruses due to their favorable properties. In this study, we identified a novel nanobody, Nanosota-9, which demonstrates high potency against a wide range of Omicron subvariants both in vitro and in a mouse model. Cryo-EM data revealed that Nanosota-9 neutralizes Omicron through a unique mechanism: two Nanosota-9 molecules crosslink two receptor-binding domains (RBDs) of the trimeric Omicron spike protein, preventing the RBDs from binding to the ACE2 receptor. This mechanism explains its strong anti-Omicron potency. Additionally, the Nanosota-9 binding epitopes on the spike protein are relatively conserved among Omicron subvariants, contributing to its broad anti-Omicron spectrum. Combined with our recently developed structure-guided in vitro evolution approach for nanobodies, Nanosota-9 has the potential to serve as the foundation for a superior anti-Omicron therapeutic.

Summary: Background: Despite significant reductions in mother-to-child HIV-1 transmission risks due to the advancements and scale-up of antiretroviral therapy (ART), the global burden of HIV-1 drug resistance (HIVDR) in treatment-naive and treatment-experienced children and adolescents remains poorly understood. In this study, we conducted a systematic review and meta-analysis to estimate the prevalence of HIVDR in these populations globally, regionally, and at the country level. Methods: We systematically searched PubMed, Embase, and Web of Science for studies reporting HIVDR in treatment-naive and treatment-experienced children and adolescents from inception to June 28, 2024. Eligible studies reported at least ten successfully genotyped cases. We excluded studies where drug resistance was not reported separately for children and adults or for treatment-naive and treatment-experienced populations. The methodological quality of eligible studies was assessed, and random-effect models were used for meta-analysis to determine the pooled overall and regimen-specific prevalence of one or more HIVDR mutations in these populations globally, regionally, or at the country level. This study is registered with PROSPERO under the number CRD42023424483. Findings: Of 2282 records identified, 136 studies (28,539 HIV-1-infected children from 52 countries) were included for analysis. The overall prevalence of HIVDR is 26.31% (95% CI, 20.76–32.25) among treatment-naive children and 74.16% (95% CI, 67.74–80.13) among treatment-experienced children (p

BackgroundLiposarcoma (LPS) is a kind of malignancy of soft tissue usually found in the retroperitoneal, limb, or neck region, and some may be detected with delayed symptoms (pain or palpable mass), and less frequently occurs in organs of the digestive system. In contrast, Dedifferentiated liposarcoma (DDLPS) is a common histological subtype of LPS. The present study reported a case of dedifferentiated liposarcoma originating in the gallbladder. Differentiated liposarcoma originating from the gallbladder is rarely reported.Case descriptionA 64-year-old female patient presented to our hospital with a painless abdominal mass. Abdominal computed tomography (CT) showed that the gallbladder had lost its normal shape, and a 9.1 cm × 7.1 cm × 12.1 cm mass was seen in the area of the gallbladder fossa and the right upper abdomen below it, which had an irregular morphology, inhomogeneous density, and nodular calcification, with marked inhomogeneous enhancement on enhancement scan. Preoperative tumor markers and liver function indicators were not abnormal. With suspicion of a giant malignant tumor of the gallbladder, she underwent a cholecystectomy combined with abdominal mass resection. After surgery, the tumor and gallbladder, were completely resected, and postoperative pathological results confirmed the diagnosis of dedifferentiated liposarcoma deriving from gallbladder. After surgery, the patient and his family refused to continue treatment. After 15 months follow-up, the patient remains asymptomatic and does not show any signs of recurrence. And she is now under continued follow - up.ConclusionsTreatment of dedifferentiated liposarcoma is still at exploratory stage, and a lack of clinical evidence for this condition might hinder access to clinical trials and studies. Currently, the treatment of choice for dedifferentiated liposarcoma remains radical resection. In the available clinical studies, there are no robust data to support clinical use of neoadjuvant and adjuvant radiochemotherapy. As with other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential future treatment.

Abstract Although Omicron RBD of SARS-CoV-2 accumulates many mutations, the backbone region (truncated RBD) of spike protein is highly conserved. Here, we designed several subunit vaccines by keeping the conserved spike backbone region of SARS-CoV-2 Omicron BA.1 subvariant (S-6P-no-RBD), or inserting the RBD of Delta variant (S-6P-Delta-RBD), Omicron (BA.5) variant (S-6P-BA5-RBD), or ancestral SARS-CoV-2 (S-6P-WT-RBD) to the above backbone construct, and evaluated their ability to induce immune responses and cross-protective efficacy against various SARS-CoV-2 variants and SARS-CoV. Among the four subunit vaccines, S-6P-Delta-RBD protein elicited broad and potent neutralizing antibodies against all SARS-CoV-2 variants tested, including Alpha, Beta, Gamma, and Delta variants, the BA.1, BA.2, BA.2.75, BA.4.6, and BA.5 Omicron subvariants, and the ancestral strain of SARS-CoV-2. This vaccine prevented infection and replication of SARS-CoV-2 Omicron, and completely protected immunized mice against lethal challenge with the SARS-CoV-2 Delta variant and SARS-CoV. Sera from S-6P-Delta-RBD-immunized mice protected naive mice against challenge with the Delta variant, with significantly reduced viral titers and without pathological effects. Protection correlated positively with the serum neutralizing antibody titer. Overall, the designed vaccine has potential for development as a universal COVID-19 vaccine and/or a pan-sarbecovirus subunit vaccine that will prevent current and future outbreaks caused by SARS-CoV-2 variants and SARS-related CoVs.

BackgroundColorectal cancer (CRC) is a leading cause of morbidity and mortality, and timely diagnosis and intervention are crucial for cancer patients. Transfer RNA-derived fragments (tRFs) play a noncoding regulatory role in organisms. Serum EV(extracellular vesicles), as an integral mediator of intercellular transmission of genetic information vesicles in Transfer RNA-derived fragment (tRF RNA), are expected to be minimally invasive diagnostic and predictive biologic factors of CRC.MethodsCollect serum samples from 205 CRC patients, and then isolate extracellular vesicles from the serum. Captured the physical morphology of EV through transmission electron microscopy. The particle size was detected by particle size assay, and protein expression on the surface of EV was verified by Western blot. Gene microarrays were screened for differentially expressed tRF-RNA. TRF RNAs were verified by qPCR for differential expression in 205 CRC patients and 201 healthy donors, assessing the CRC diagnostic efficiency by area under the curve (AUC).ResultsCompared with 201 healthy donors, CRC patients experienced significantly down-regulated serum EV 3’tRF-ThrCGT while significantly up-regulated 3’tRF-mtlleGAT. Serum EV 3’tRF-ThrCGT and 3’tRF-mtlleGAT predictive diagnostic efficiency: 0.669 and 0.656, and the combination of CEA and CA724 predictive diagnostic efficiency was 0.938.ConclusionThe study data showed that 3’tRF-ThrCGT and 3’tRF-mtlelGAT can be minimally invasive diagnostic CRC indicators. The combination of tumor markers CEA and CA724 has important diagnostic significance.

The issue of whether CoCrFeNi is a single-phase or dual-phase high-entropy alloy (HEA) has long been in dispute. In this study, CoCrFeNi has been verified to be a dual-phase HEA composed of dendritic phases with an FCC structure and inter-dendritic phases with a BCC structure. The BCC phases within inter-dendritic regions are identified as Cr3O oxides which form inevitably under the arc-melting process. Undercooling treatment under a strong magnetic field can regulate the composition and precipitation of the BCC phase, refine the grain size, and enhance the solid solubility, consequently, the mechanical performances of CoCrFeNi HEA are effectively enhanced.

Abstract Previous work comparing safety and effectiveness outcomes for new initiators of angiotensin converting‐enzyme inhibitors (ACEi) and thiazides demonstrated more favorable outcomes for thiazides, although cohort definitions allowed for addition of a second antihypertensive medication after a week of monotherapy. Here, we modify the monotherapy definition, imposing exit from cohorts upon addition of another antihypertensive medication. We determine hazard ratios (HR) for 55 safety and effectiveness outcomes over six databases and compare results to earlier findings. We find, for all primary outcomes, statistically significant differences in effectiveness between ACEi and thiazides were not replicated (HRs: 1.11, 1.06, 1.12 for acute myocardial infarction, hospitalization with heart failure and stroke, respectively). While statistical significance is similarly lost for several safety outcomes, the safety profile of thiazides remains more favorable. Our results indicate a less striking difference in effectiveness of thiazides compared to ACEi and reflect some sensitivity to the monotherapy cohort definition modification.

The noise that comes from finite element simulation often causes the model to fall into the local optimal solution and over fitting during optimization of generator. Thus, this paper proposes a Gaussian Process Regression (GPR) model based on Conditional Likelihood Lower Bound Search (CLLBS) to optimize the design of the generator, which can filter the noise in the data and search for global optimization by combining the Conditional Likelihood Lower Bound Search method. Taking the efficiency optimization of 15 kW Permanent Magnet Synchronous Motor as an example. Firstly, this method uses the elementary effect analysis to choose the sensitive variables, combining the evolutionary algorithm to design the super Latin cube sampling plan; Then the generator-converter system is simulated by establishing a co-simulation platform to obtain data. A Gaussian process regression model combing the method of the conditional likelihood lower bound search is established, which combined the chi-square test to optimize the accuracy of the model globally. Secondly, after the model reaches the accuracy, the Pareto frontier is obtained through the NSGA-II algorithm by considering the maximum output torque as a constraint. Last, the constrained optimization is transformed into an unconstrained optimizing problem by introducing maximum constrained improvement expectation (CEI) optimization method based on the re-interpolation model, which cross-validated the optimization results of the Gaussian process regression model. The above method increase the efficiency of generator by 0.76% and 0.5% respectively; And this method can be used for rapid modeling and multi-objective optimization of generator systems.

Abstract Pursuit of improved living quality has stimulated great demand for high-performance conformal healthcare devices in modern human society. However, manufacturing of efficient, comfortable and stretchable biomedical apparatus faces huge challenges using traditional materials. Liquid metals (LMs) show remarkable potential to solve this problem due to their extraordinary biocompatibility, stretchability, thermal and electrical conductivity. In recent years, tremendous explorations have attempted to make stretchable biomedical devices with LMs. Herein, we review the stretchable LM-based biomedical devices on the topics of disease treatment and human function augmenting. The representative and up-to-date neural interfaces, alloy cement, e-vessels, soft heaters, exoskeletons, and e-skins are summarized. The existing issues of LMs applied for biomedical devices are also discussed. This review can provide guidance for the follow-up research in LM-based biomedical devices.

Since the COVID-19 outbreak, raccoon dogs have been suggested as a potential intermediary in transmitting SARS-CoV-2 to humans. To understand their role in the COVID-19 pandemic and the species barrier for SARS-CoV-2 transmission to humans, we analyzed how their ACE2 protein interacts with SARS-CoV-2 spike protein. Biochemical data showed that raccoon dog ACE2 is an effective receptor for SARS-CoV-2 spike protein, though not as effective as human ACE2. Structural comparisons highlighted differences in the virus-binding residues of raccoon dog ACE2 compared to human ACE2 (L24Q, Y34H, E38D, T82M, R353K), explaining their varied effectiveness as receptors for SARS-CoV-2. These variations contribute to the species barrier that exists between raccoon dogs and humans regarding SARS-CoV-2 transmission. Identifying these barriers can help assess the susceptibility of other mammals to SARS-CoV-2. Our research underscores the potential of raccoon dogs as SARS-CoV-2 carriers and identifies molecular barriers that affect the virus's ability to jump between species.

Abstract Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.

The distribution of diffuse spot energy can be used to sensitively evaluate the aberrations and defects of optical systems. Therefore, the objective and quantitative measurement of diffuse spot parameters is an important means to control the detection quality of space debris detection systems. At present, the existing optical system dispersion measurement method can only judge whether the energy distribution meets the index. However, these methods ca not provide an objective quantitative basis to guide the installation process. To solve this problem, a mathematical simulation model of 3D multi-phase sub-pixel PSF distribution is proposed. According to the relation between the CCD target plane and the theoretical image plane (focal plane, defocus, and deflection), the diffuse spot distribution of the optical system is simulated with different phase combinations. Then, Pearson Correlation Coefficient (PCC) is used to evaluate the matching similarity of the diffuse spot image. The simulation results show that when the PCC is greater than 0.96, the distribution of the two diffuse spots can be identified as matching. This also confirms the accuracy of the proposed PSF model. Then, the focusing deviation of the system being tested can be analyzed according to the phase size of the diffuse spot simulation image. This method can quickly and accurately guide the focal surface installation and testing of the system. Therefore, the purpose of improving the detection accuracy of space debris is achieved. It also provides a quantitative basis for the engineering application of optical detection systems in the future.

Brandt’s voles (Lasiopodomys brandtii), one of the main non-hibernating rodent species in the typical grassland of Inner Mongolia, live in groups and have the behavioral habit of hoarding food in underground warehouses in autumn to prepare for the winter food shortage ahead. The division of labor and cooperation are typical behavior patterns of gregarious mammals, but it is unclear whether Brandt’s voles exercise a division of labor in food hoarding before overwintering. To explore the division of food hoarding in Brandt’s voles during the autumn period, three treatments, namely added food, added food + competition, and control, were set up with three replicates. An infrared camera was positioned to observe and record the behavior of Brandt’s voles under different treatments. Next, behavioral experiments regarding food-hoarding division were performed on individuals. The results showed that (1) Brandt’s voles had two types of hoarding behavior, namely high food hoarding and low food hoarding, but not all individuals displayed hoarding behavior. (2) In all treatments, feeding behavior, which was the most important type of behavior, accounted for the highest proportion of all behaviors. (3) There was no significant difference in body weight and sex between high- and low-food-hoarding individuals of Brandt’s voles, and there was no significant difference between high- and low-food-hoarding individuals in other divisions of labor either. (4) There was no significant difference in inquiry ability between high- and low-food-hoarding groups, but there was a significant difference in spatial memory. High-food-hoarding individuals had greater spatial memory. In summary, Brandt’s voles had two types of hoarding behavior: high food hoarding and low food hoarding. Furthermore, high-food-hoarding individuals had greater spatial memory.

Forests play a crucial role in maintaining the integrity of natural ecosystems. Accurate mapping of windfall damages following storms is essential for effective post-disaster management. While remote sensing image classification offers substantial advantages over ground surveys for monitoring changes in forests, it encounters several challenges. Firstly, training samples in classification algorithms are typically selected through pixel-based random sampling or manual regional sampling. This approach struggles with accurately modeling complex patterns in high-resolution images and often results in redundant samples. Secondly, the limited availability of labeled samples compromises the classification accuracy when they are divided into training and test sets. To address these issues, two innovative approaches are proposed in this paper. The first is a new sample selection method which combines block-based sampling with spatial features extracted by single or multiple windows. Second, a new evaluation criterion is proposed by using the homomorphic hypothesis margin map with out-of-bag (OOB) accuracy. The former can not only assess the confidence level of each pixel category but also make regional boundaries clearer, and the latter can replace the test set so that all samples can be used for change detection. The experimental results show that the OOB accuracy obtained by spatial features with whole block sampling was 7.2% higher than that obtained by spectral features with pixel-based sampling and 2–3% higher than that for block center sampling, of which the highest value reached 98.8%. Additionally, the feasibility of identifying storm-damaged forests using only post-storm images has been demonstrated.

As the most abundant group of mammals, rodents possess a very rich ecotype, which makes them ideal for studying the relationship between diet and host gut microecology. Zokors are specialized herbivorous rodents adapted to living underground. Unlike more generalized herbivorous rodents, they feed on the underground parts of grassland plants. There are two species of the genus Myospalax in the Eurasian steppes in China: one is Myospalax psilurus, which inhabits meadow grasslands and forest edge areas, and the other is M. aspalax, which inhabits typical grassland areas. How are the dietary choices of the two species adapted to long-term subterranean life, and what is the relationship of this diet with gut microbes? Are there unique indicator genera for their gut microbial communities? Relevant factors, such as the ability of both species to degrade cellulose, are not yet clear. In this study, we analyzed the gut bacterial communities and diet compositions of two species of zokors using 16S amplicon technology combined with macro-barcoding technology. We found that the diversity of gut microbial bacterial communities in M. psilurus was significantly higher than that in M. aspalax, and that the two species of zokors possessed different gut bacterial indicator genera. Differences in the feeding habits of the two species of zokors stem from food composition rather than diversity. Based on the results of Mantel analyses, the gut bacterial community of M. aspalax showed a significant positive correlation with the creeping-rooted type food, and there was a complementary relationship between the axis root-type-food- and the rhizome-type-food-dominated (containing bulb types and tuberous root types) food groups. Functional prediction based on KEGG found that M. psilurus possessed a stronger degradation ability in the same cellulose degradation pathway. Neutral modeling results show that the gut flora of the M. psilurus has a wider ecological niche compared to that of the M. aspalax. This provides a new perspective for understanding how rodents living underground in grassland areas respond to changes in food conditions.

Brandt's Vole (Lasiopodomys brandtii) is one of the most abundant rodent species in the grasslands of Inner Mongolia, China, and one of the main carriers of Yersinia pestis, the plague bacterium. There have been several instances of plague transmission among L. brandtii, and all of their dominant flea species are known carriers of plague. Little work has been done to understand the regulation of flea abundance on L. brandtii by biotic and abiotic factors. Here, we examine the impacts of host and climate variation on flea abundance on L. brandtii in May, July, and September of 2021 in the East Ujumqin Banner, Xilinhot City, Inner Mongolia Autonomous Region. We arrived at the following conclusions: 1) There were 8 flea species representing 2 families and 5 genera collected from L. brandtii, and Frontopsylla luculenta, Neopsylla pleskei orientalis, and Amphipsylla primaris mitis were most common. 2) Host body weight, host age, season, temperature, and humidity are key factors influencing flea abundance on L. brandtii. 3) Flea species vary in their respective responses to factors.

ABSTRACTThe discovery of functional amyloids in bacteria dates back several decades, and our understanding of the Escherichia coli curli biogenesis system has gradually expanded over time. However, due to its high aggregation propensity and intrinsically disordered nature, CsgA, the main structural component of curli fibrils, has eluded comprehensive structural characterization. Recent advancements in cryo-electron microscopy (cryo-EM) offer a promising tool to achieve high-resolution structural insights into E. coli CsgA fibrils. In this study, we outline an approach to addressing the colloidal instability challenges associated with CsgA, achieved through engineering and electrostatic repulsion. Then, we present the cryo-EM structure of CsgA fibrils at 3.62 Å resolution. This structure provides new insights into the cross-β structure of E. coli CsgA. Additionally, our study identifies two distinct spatial arrangements within several CsgA fibrils, a 2-CsgA-fibril pair and a 3-CsgA-fibril bundle, shedding light on the intricate hierarchy of the biofilm extracellular matrix and laying the foundation for precise manipulation of CsgA-derived biomaterials.IMPORTANCEThe visualization of the architecture of Escherichia coli CsgA amyloid fibril has been a longstanding research question, for which a high-resolution structure is still unavailable. CsgA serves as a major subunit of curli, the primary component of the extracellular matrix generated by bacteria. The support provided by this extracellular matrix enables bacterial biofilms to resist antibiotic treatment, significantly impacting human health. CsgA has been identified in members of Enterobacteriaceae, with pathogenic E. coli being the most well-known model system. Our novel insights into the structure of E. coli CsgA protofilaments form the basis for drug design targeting diseases associated with biofilms. Additionally, CsgA is widely researched in biomaterials due to its self-assembly characteristics. The resolved spatial arrangements of CsgA amyloids revealed in our study will further enhance the precision design of functional biomaterials. Therefore, our study uniquely contributes to the understanding of CsgA amyloids for both microbiology and material science.

The relationship between the local structures and the thermodynamic properties of metallic liquids has been a fundamental issue, which significantly impacts the comprehensive performances of metallic materials. The temperature-induced structure evolution in CoxBy alloy liquids, involving CoB, Co2B, Co3B, and Co23B6, was investigated using ab initio molecular dynamics simulations. The results show that the clusters of icosahedral-like polyhedrons are found predominantly in all alloys at low temperature, while the heating induces the decrease in ideal icosahedral and the increase in defected icosahedral. At high temperature, the polyhedron clusters decrease significantly and the ideal icosahedra transforms into smaller short-range polyhedrons, signifying the temperature-induced chemical structure change from long-range to short-range ordering. The aggregation of B atoms at high temperature is confirmed by atomic configuration, charge density, and B-centered Voronoi polyhedrons, and the α-Co single phase is observed below 1600 K. This study is helpful for understanding the local structure variability in eutectic Co-B alloys and guiding solidification path in theory.

PurposeThe aim of this study is to provide treatment for patients with urinary incontinence at different periods after radical prostatectomy.MethodsThe PubMed, Embase, Cochrane, and Web of Science were searched for all literature on the effectiveness on urinary control after radical prostate cancer between the date of database creation and 15 November 2023 and performed a quality assessment. A network meta-analysis was performed using RevMan 5.3 and Stata 17.0 software and evaluated using the surface under the cumulative ranking curve.ResultsThe results of the network meta-analysis showed that pelvic floor muscle therapy including biofeedback with professional therapist–guided treatment demonstrated better results at 1 month to 6 months; electrical stimulation, biofeedback, and professional therapist guidance may be more effective at 3 months of treatment; professional therapist–guided recovery may be less effective at 6 months of treatment; and combined therapy demonstrated better results at 1 year of treatment. During the course of treatment, biofeedback with professional therapist–guided treatment may have significant therapeutic effects in the short term after surgery, but, in the long term, the combination of multiple treatments (pelvic floor muscle training+ routine care + biofeedback + professional therapist–guided treatment + electrical nerve stimulation therapy) may address cases of urinary incontinence that remain unrecovered long after surgery.ConclusionIn general, all treatment methods improve the different stages of functional recovery of the pelvic floor muscles. However, in the long term, there are no significant differences between the treatments. Given the cost-effectiveness, pelvic floor muscle training + routine care + biofeedback + professional therapist–guided treatment + electrical nerve stimulation therapy within 3 months and pelvic floor muscle + routine care after 3 months may be a more economical option to treat urinary incontinence.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=331797, identifier CRD42022331797.

Dipus sagitta is a major rodent found in arid environments and desert areas. They feed on plant seeds, young branches and some small insects, and have hibernating habits. Peak Dipus sagitta numbers impact the construction of the plant community in the environment, but also have a human impact as these rodents carry a variety of parasitic fleas capable of spreading serious diseases to humans. Based on 216 present distribution records of Dipus sagitta and seven environmental variables, this article simulates the potential distribution of Dipus sagitta during the Last Glacial Maximum, the mid-Holocene, the present and the future (2070s, RCP4.5, RCP8.5). This study also analyzes the geographic changes of the population distribution and evaluates the importance of climate factors by integrating contribution rate, replacement importance value and the jackknife test using the MaxEnt model. In this study, we opted to assess the predictive capabilities of our model using the receiver operating characteristic (ROC) and partial receiver operating characteristic (pROC) metrics. The findings indicate that the AUC value exceeds 0.9 and the AUC ratio is greater than 1, indicating superior predictive performance by the model. The results showed that the main climatic factors affecting the distribution of the three-toed jerboa were precipitation in the coldest quarter, temperature seasonality (standard deviation), and mean annual temperature. Under the two warming scenarios of the mid-Holocene and the future, there were differences in the changes in the distribution area of the three-toed jerboa. During the mid-Holocene, the suitable distribution area of the three-toed jerboa expanded, with a 93.91% increase in the rate of change compared to the Last Glacial Maximum. The size of the three-toed jerboa’s habitat decreases under both future climate scenarios. Compared to the current period, under the RCP4.5 emission scenario, the change rate is −2.96%, and under the RCP8.5 emission scenario, the change rate is −7.41%. This indicates a trend of contraction in the south and expansion in the north. It is important to assess changes in the geographic population of Dipus sagitta due to climate change to formulate population control strategies of these harmful rodents and to prevent and control the long-distance transmission of zoonotic diseases.

Prostate cancer is a common malignancy in urology which often develops into castration-resistant prostate cancer (CRPC) after hormone therapy. Studies have shown that the mechanism of its occurrence is related to androgen receptor splice variants (AR splice variants). This work employs a bibliometric approach to explore the knowledge structure and emerging trends of AR variants in prostate cancer. The literature from 2000 to 2021 was obtained from Web of Science Core Collection (WoSCC), and the results were analyzed and visualized via CiteSpace and VOSviewer regarding publication number, citation number, country, region, institution, journal, author, keyword and reference. A total of 1503 publications were obtained. The number of publications and citations in this field is increasing. United States is the most prominent country, and University of Washington is the most influential institution in terms of this research field. European Urology is the most authoritative journal regarding this field. Gleave, Martin is the most productive author, and collaborated closely with others having centrality >0.1. The keywords abiraterone and AR-V7 have the strongest citation bursts in recent years and continuing to the end of 2021 which indicate the trend and further research directions. The most cited papers and co-cited references were related to the clinical significance of AR-V7 and its mechanism of promoting CRPC. This study used visualization software CiteSpace and VOSviewer to analyze the current status and the research trends of AR variants in prostate cancer (PCa) over the past 20 years. The findings can identify research hotspots and reveal future research directions.

BackgroundRecent an observational study has suggested a potential connection between gut microbiota (GM) and peptic ulcer diseases (PUDs), particularly gastric ulcer (GU) and duodenal ulcer (DU). However, the causal connection remains unsure.MethodsA two-sample Mendelian randomization (MR) is carried out to explore the connection between the GM and DU or GU. Data on the GM comes from the MiBioGend database, and GU or DU data are based on the FinnGen database. One group of single nucleotide polymorphisms (SNPs) (P < 5 × 10−8) are served as instrumental variables (IVs). To obtain a more comprehensive conclusion, the other SNPs (P < 1 × 10−5) are selected as IVs. Inverse variance weighting (IVW) is used to determine the causal relationship.ResultsAt the level of P < 1 × 10−5, the IVW analysis suggests that Clostridiaceae1, Butyriccoccus, and Peptcoccus have harmful effects on GU, while LachnospiraceaeUCG004 and MollicutesRF9 have beneficial effects on GU. Then, in the case of DU, the IVW analysis suggested that Lentisphaeria, Negativicutes, Clostridiaceae1, ClostridiumseMnsustricto1, ErysipelotrichaceaeUCG003, LachnospiraceaeNC2004group, Selenomonadale, Victivallales, and Lentisphaerae have harmful effects, while Catenibacterium, Escherichia.Shigella, LachnospiraceaeUCG008, and Sutterella have beneficial effects. When P < 5 × 10−8, IVW analysis suggests that GM has no significant influence on GU or DU.ConclusionThis two-sample MR indicates a causal relationship between GM and GU or DU.

Hemp (Cannabis sativa L.) is increasingly gaining traction as a novel and sustainable source of plant protein. Accordingly, the aim of this study was to investigate the effectiveness of two protein extraction methods, alkaline extraction coupled with isoelectric precipitation (AE-IEP) and salt extraction coupled with ultrafiltration (SE-UF) in producing hemp protein isolates (pH-HPI and salt-HPI) with high purity and yield. Structural characterization as impacted by extraction method and cultivar was performed and related to functional performance and nutritional quality. Both extraction methods, with carefully selected parameters, resulted in HPI with high purity (86.6–88.1% protein) and protein extraction yields (81.6–87.3%). All HPI samples had poor solubility (∼9–20%) at neutral pH compared to commercial soy protein and pea protein isolates (cSPI, cPPI). A relatively high surface hydrophobicity and low surface charge contributed to such poor solubility of HPI. However, HPI demonstrated similar solubility at acidic pH (50–67%) and comparable gel strength (up to 24 N) to cSPI. Comparing experimental amino acid composition to the theoretical amino acid distribution in hemp protein provided insights to the functional performance of the protein isolates. While pH-HPI demonstrated better functionality than salt-HPI, minimal structural, functional, and nutritional differences were noted among the pH-HPI samples extracted from four different cultivars. Overall, results from this work could be used to guide future attempts to further develop successful protein extraction processes, and to provide valuable insights to propel breeding efforts that target enhanced hemp protein characteristics for food applications.

Chronic pelvic pain syndrome (CPPS) is a common complication of prostatitis, which was associated with the pathological depolarization of macrophage and the neuroinflammation. However, its underlying reason is far from clear and few effective treatments is applicable. In this study, we tested the effect of obacunone (Oba), a highly oxygenated triterpenoid, on CPPS. The experimental autoimmune prostatitis (EAP) was induced by subcutaneous injection of heterologous prostate homogenate in mice. We found that EAP led to prostatodynia, neuronal activation of spinal dorsal horn, and the pro-inflammatory depolarization of macrophage within prostate, which was significantly alleviated by oral administration of Oba in a dose-dependent manner. Mechanistically, EAP-induced production of IL-6 on prostatic macrophage was suppressed by Oba. Moreover, co-administration of Oba and MIF inhibitor ISO-1 did not lead to additive effect when compared with either alone. In summary, we conclude that Oba prevents the production of macrophage-derived pro-inflammatory factors by inhibiting MIF, which eventually alleviates CPPS after prostatitis.

SARS-CoV-2 spike protein plays a key role in mediating viral entry and inducing host immune responses. It can adopt either an open or closed conformation based on the position of its receptor-binding domain (RBD). It is yet unclear what causes these conformational changes or how they influence the spike’s functions. Here, we show that Lys417 in the RBD plays dual roles in the spike’s structure: it stabilizes the closed conformation of the trimeric spike by mediating inter-spike–subunit interactions; it also directly interacts with ACE2 receptor. Hence, a K417V mutation has opposing effects on the spike’s function: it opens up the spike for better ACE2 binding while weakening the RBD’s direct binding to ACE2. The net outcomes of this mutation are to allow the spike to bind ACE2 with higher probability and mediate viral entry more efficiently, but become more exposed to neutralizing antibodies. Given that residue 417 has been a viral mutational hotspot, SARS-CoV-2 may have been evolving to strike a balance between infection potency and immune evasion, contributing to its pandemic spread.

Abstract Background Frailty is the third most common complication of diabetes after macrovascular and microvascular complications. The aim of this study was to develop a validated risk prediction model for frailty in patients with diabetes. Methods The research used data from the China Health and Retirement Longitudinal Study (CHARLS), a dataset representative of the Chinese population. Twenty-five indicators, including socio-demographic variables, behavioral factors, health status, and mental health parameters, were analyzed in this study. The study cohort was randomly divided into a training set and a validation set at a ratio of 70 to 30%. LASSO regression analysis was used to screen the variables for the best predictors of the model based on a 10-fold cross-validation. The logistic regression model was applied to explore the associated factors of frailty in patients with diabetes. A nomogram was constructed to develop the prediction model. Calibration curves were applied to evaluate the accuracy of the nomogram model. The area under the receiver operating characteristic curve and decision curve analysis were conducted to assess predictive performance. Results One thousand four hundred thirty-six patients with diabetes from the CHARLS database collected in 2013 (n = 793) and 2015 (n = 643) were included in the final analysis. A total of 145 (10.9%) had frailty symptoms. Multivariate logistic regression analysis showed that marital status, activities of daily living, waist circumference, cognitive function, grip strength, social activity, and depression as predictors of frailty in people with diabetes. These factors were used to construct the nomogram model, which showed good concordance and accuracy. The AUC values of the predictive model and the internal validation set were 0.912 (95%CI 0.887–0.937) and 0.881 (95% CI 0.829–0.934). Hosmer–Lemeshow test values were P = 0.824 and P = 0.608 (both > 0.05). Calibration curves showed significant agreement between the nomogram model and actual observations. ROC and DCA indicated that the nomogram had a good predictive performance. Conclusions Comprehensive nomogram constructed in this study was a promising and convenient tool to evaluate the risk of frailty in patients with diabetes, and contributed clinicians to screening the high-risk population.

Hypervirulent Klebsiella pneumoniae (hvKp) is a notorious clinical pathogen that is more likely to cause severe primary and metastatic abscesses. The dissemination of antimicrobial-resistant hvKp isolates has been reported worldwide, posing a great challenge and severe clinical threat. However, the mechanisms of antimicrobial-resistant hvKp isolates prevalent worldwide are not well precise. Outer membrane vesicles (OMVs) secreted from gram-negative bacteria are an important vehicle for delivering effector molecules inter- and intra-species. To explore whether OMVs as the vector of virulence genes horizontal transfer among Klebsiella pneumoniae and to explain the potential mechanism for the development of antimicrobial-resistant hvKp isolates, we isolated OMVs from hvKp and classical Klebsiella pneumoniae (cKp) by sequential differential centrifugation, respectively. Then, the characteristics and contents of hvKp-OMVs and cKp-OMVs were analyzed. These hvKp-OMVs contain virulence genes, which could be transferred from hvKp horizontally to extended-spectrum beta lactamase (ESBL)-producing cKp, leading to the production of antimicrobial-resistant hypervirulent transformants. Further experiments confirmed the transformants exhibited antimicrobial resistance and hypervirulent phenotypes in vitro and in vivo. In short, this work demonstrated that hvKp-OMVs facilitated virulence genes transfer, allowing an increase in the virulence level of ESBL-producing cKp and providing a new mechanism for the emergence of antimicrobial-resistant hvKp isolates.

Resource partitioning may allow species coexistence. Sand dunes in the typical steppe of Alxa Desert Inner Mongolia, China, consisting of desert, shrub, and grass habitats, provide an appropriate system for studies of spatial niche partitioning among small mammals. In this study, the spatial niche characteristics of four rodents, Orientallactaga sibirica, Meriones meridianus, Dipus sagitta, and Phodopus roborovskii, and their responses to environmental changes in the Alxa Desert were studied from 2017 to 2021. Using the capture-mark-recapture method, we tested if desert rodents with different biological characteristics and life history strategies under heterogeneous environmental conditions allocate resources in spatial niches to achieve sympatric coexistence. We investigated the influence of environmental factors on the spatial niche breadth of rodents using random forest and redundancy analyses. We observed that the spatial niche overlap between O. sibirica and other rodents is extremely low (overlap index ≤ 0.14). P. roborovskii had the smallest spatial niche breadth. Spatial niche overlap was observed in two distinct species pairs, M. meridianus and D. sagitta, and P. roborovskii and D. sagitta. The Pielou evenness index of rodent communities is closely related to the spatial distribution of rodents, and the concealment of habitats is a key factor affecting the spatial occupation of rodents.

It is well-established that there are trillions of gut microbiota (GM) in the human gut. GM and its metabolites can reportedly cause cancer by causing abnormal immune responses. With the development of sequencing technology and the application of germ-free models in recent years, significant inroads have been achieved in research on GM and microbiota-related metabolites. Accordingly, the role and mechanism of GM in colorectal cancer (CRC) development have been gradually revealed. Traditional Chinese medicine (TCM) represents an important source of natural medicines and herbal products, with huge potential as anti-CRC agents. The potential application of TCM to target gut microbes for the treatment of colorectal cancer represents an exciting area of investigation.

Objective To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.Participants 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.Exposure The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measures The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.Results 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.Conclusions Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.

BackgroundUndifferentiated pleomorphic sarcoma (UPS) is a highly malignant soft tissue sarcoma with a poor prognosis and no clear effective clinical means for treatment, and there has been no significant progress in research within this field in recent years. This study aimed to investigate the epidemiology, etiology, clinical features, diagnostic modalities, various treatment modalities, and prognosis of retroperitoneal undifferentiated pleomorphic sarcoma and to contribute to the clinical management of this type of disease. In this study, we report a case of undifferentiated pleomorphic sarcoma with a primary origin in the retroperitoneum. Undifferentiated pleomorphic sarcoma occurring in the retroperitoneum is rarely reported.Case descriptionA 59-year-old man with abdominal distension and pain for 4 months presented to our hospital after the failure of conservative treatment. A 9.6 cm by 7.4 cm mass in the left retroperitoneum was found on a CT scan of the whole abdomen with three degrees of enhancement. After surgical treatment, the tumor and the left kidney were completely removed, and pathological examination and genetic sequencing showed an apparent undifferentiated pleomorphic sarcoma. The patient subsequently declined follow-up treatment and is currently alive and well.ConclusionsAt the current level of clinical technology, the treatment of undifferentiated pleomorphic sarcoma is still in the exploratory stage, and the scarcity of clinical cases of this disease may have hindered the acquisition of clinical trials and research data for this disease. At present, the first choice of treatment for undifferentiated pleomorphic sarcoma is still radical resection. In the existing clinical studies, there are no strong data to support the effect of preoperative neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy in clinical practice. Similar to other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential treatment for this disease in the future. Targeted therapy for this disease still needs further exploration, and we need more reports on related diseases to promote future treatment and research on this disease.

The down raw materials collected from the slaughterhouses generally adhered with an excessive amount of dust and complex stains which hinder them to be utilized directly for down textiles processing. Water washing is an important core process of down raw material processing for dust removal, decontamination, and sterilization of down fibers. However, there is no standard method to analyze the stain category and content of down raw materials, so it can only rely on traditional experience to wash down, which may cause problems including insufficient or excessive washing, and serious damage to the quality of down fibers. Thus, this study has been specifically designed and developed a method dedicated to categorizing stain types and content of down raw materials. This novel design process is named as “one blow and two washes”, which is composed of three steps to analyze dust content, water-soluble stains, and grease stains in down raw material more accurately. In this experiment, the stain analysis of six different sources of down raw materials was carried out, scanning electron microscope (SEM) and super depth of field 3D microscope system were used to characterize down samples. The results showed that the “one blow and two washes” method could accurately be used to distinguish stain categories of different sources of down raw material with a small average variance value and a coefficient of variation less than 12%, indicating that this experimental method has high reliability and good reproducibility. These research results will provide an important basis for the design of the washing agent dosage and process parameters for raw down, which is expected to achieve the precise washing process of raw down and improve the quality of down.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 72–4 (CA72–4) are commonly used markers for colorectal cancer (CRC) in clinical applications. However, low positivity rate and sensitivity limits their clinical effectiveness. In this study, we explored the potential of C–reactive protein (CRP) and fibrinogen to improve the diagnostic efficiency of traditional biomarkers of CRC. The concentrations of CRP and fibrinogen in plasma were significantly higher in CRC patients compared with benign or healthy controls. The area under the ROC curves (AUCs) showed that the diagnostic efficacy of CRP and fibrinogen was 0.745 (95% CI: 0.712–0.779) and 0.699 (95% CI: 0.663–0.734), respectively. AUC increased to 0.750 (95% CI: 0.716–0.784) when CRP and fibrinogen were combined. It also further improved to 0.889 (95% CI: 0.866–0.913) when CRP and fibrinogen were integrated with CEA and CA72–4. Moreover, this combination increased the maximum area under AUC to 0.857 (95% CI: 0.830–0.883), which effective differentiated CRC from benign disease. Overall, this study found that CRP and fibrinogen were highly expressed in the plasma of CRC patients, suggesting their potential to improve the diagnostic efficiency of traditional biomarkers of CRC.

Grassland is not only an important part of the terrestrial ecosystem with multiple ecological functions, but also an important base for Chinese herdsmen to produce and live. However, the occurrence and spread of rodent infestation reduces the biodiversity and productivity of grassland ecosystems. It also severely threatens human life, health, and biosecurity through disease transmission. In this study, we explored the ability of the nanocomposite sterilant ND-1 to control grassland rodent populations. Semi-closed experimental and control plots were established in the desert area of Alashan, Inner Mongolia, China. In spring 2018, the nanocomposite sterile ND-1 (Nongda-1) was introduced once, and the control effect of ND-1 on the growth of the wild population of midday gerbils was measured for two years. We show that ND-1 significantly reduced the population of midday gerbils in the experimental area, with a negative population growth rate. In addition, in the second year, the ratio of female midday gerbils to sub-adults in the experimental area was significantly lower than that in the control area, which resulted in a significant difference in the sex ratio of midday gerbils. There were significantly fewer females than males, and the population growth of midday gerbils in the experimental area was significantly inhibited. ND-1 had no significant effect on the home range of midday gerbils, and sterile individuals continued to occupy the home range and consume resources. Therefore, ND-1 reduced the number of female midday gerbils during the breeding period and the sex ratio and population density and altered the age structure of the wild population. Additionally, competition between sterile and normal individuals had a significant control effect on the growth of wild populations. Our studies demonstrate the significance of ND-1 in the sustainable control of grassland rodent pests, with the potential for limiting grassland rodent damage in the future.

Summary: Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

The compressibility and rebound properties of sand reinforced with polymer and fibers were studied with respect to polymer content, dry density, and types and content of fibers using laboratory standard consolidation experiments. The following conclusions are drawn: (1) with the increase in polymer, the compressive coefficient of reinforced sand decreases gradually. Up to 4%, the compressive coefficient decreases slowly and the resilient rate keeps increasing; (2) with the increase in dry density, the compression coefficient decreases rapidly at first and then changes slowly. Up to 1.55 g/cm3, the compression coefficient changes slowly, while the resilient rate keeps increasing; (3) with the increase in fiber content, the compressive coefficient increases and the compressive characteristics of the sand after adding polypropylene fibers become stronger than those of the sand with addition of sisal fibers. The resilient rate of the reinforced sand keeps increasing and the sand reinforced with sisal fiber has a higher resilient rate; (4) the polymer forms a parallel connection model between sand particles, and the curing film can fill the pore between particles. A spatial stereo structure is formed within the sand mixed with fibers reducing the compression characteristics and increasing the resilience under larger vertical loads.