Search

Abstract Claudin18.2 (CLDN18.2) is overexpressed in cancers of the digestive system, rendering it an ideal drug target for antibody-drug conjugates (ADCs). Despite many CLDN18.2-directed ADCs undergoing clinical trials, the inconclusive underlying mechanisms pose a hurdle to extending the utility of these agents. In our study, αCLDN18.2-MMAE, an ADC composed of an anti-CLDN18.2 monoclonal antibody and the tubulin inhibitor MMAE, induced a dose-dependent apoptosis via the cleavage of caspase-9/PARP proteins in CLDN18.2-positive gastric cancer cells. It was worth noting that autophagy was remarkably activated during the αCLDN18.2-MMAE treatment, which was characterized by the accumulation of autophagosomes, the conversion of autophagy marker LC3 from its form I to II, and the complete autophagic flux. Inhibiting autophagy by autophagy inhibitor LY294002 remarkably enhanced αCLDN18.2-MMAE-induced cytotoxicity and caspase-mediated apoptosis, indicating the cytoprotective role of autophagy in CLDN18.2-directed ADC-treated gastric cancer cells. Combination with an autophagy inhibitor significantly potentiated the in vivo antitumoral efficacy of αCLDN18.2-MMAE. Besides, the Akt/mTOR pathway inactivation was demonstrated to be implicated in the autophagy initiation in αCLDN18.2-MMAE-treated gastric cancer cells. In conclusion, our study highlighted a groundbreaking investigation into the mechanism of the CLDN18.2-directed ADC, focusing on the crucial role of autophagy, providing a novel insight to treat gastric cancer by the combination of CLDN18.2-directed ADC and autophagy inhibitor.

BackgroundObservational studies have suggested a potential relationship between birthweight and telomere length. However, the causal link between these two parameters remains undefined. In this study, we use Mendelian Randomization (MR). This method employs genetic variants as instrumental variables, to explore the existence of causal associations and elucidate the causal relationship between birth weight and telomere length.MethodsWe used 35 single nucleotide polymorphisms (SNPs) as instrumental variables for birth weight. These SNPs were identified from a meta-analysis involving 153,781 individuals. Furthermore, we obtained summary statistics for telomere length from a study conducted on 472,174 United Kingdom Biobank participants. To evaluate the causal estimates, we applied the random effect inverse variance weighted method (IVW) and several other MR methods, such as MR-Egger, weighted median, and MR-PRESSO, to verify the reliability of our findings.ResultsOur analysis supports a significant causal relationship between genetically predicted birth weight and telomer3e length. The inverse variance weighted analysis results for birth weight (Beta = 0.048; 95%CI = 0.023 to 0.073; p < 0.001) corroborate this association.ConclusionOur study provides robust evidence supporting a causal link between higher birth weight and longer telomere length.

Solid-state electrolytes (SSEs), particularly garnet-type Li6.4La3Zr1.4Ta0.6O12 (LLZTO), offer high stability and a wide electrochemical window. However, their grain boundaries limit ionic conductivity, necessitating high-temperature sintering for improved performance. Yet, this process results in brittle electrolytes prone to fracture during manufacturing. To address these difficulties, solvent-free solid-state electrolytes with a polyacrylonitrile (PAN) coating on LLZTO particles are reported in this work. Most notably, the PAN-coated LLZTO (PAN@LLZTO) electrolyte demonstrates self-supporting characteristics, eliminating the need for high-temperature sintering. Importantly, the homogeneous polymeric PAN coating, synthesized via the described method, facilitates efficient Li+ transport between LLZTO particles. This electrolyte not only achieves an ionic conductivity of up to 2.11 × 10−3 S cm−1 but also exhibits excellent interfacial compatibility with lithium. Furthermore, a lithium metal battery incorporating 3% PAN@LLZTO-3%PTFE as the solid-state electrolyte and LiFePO4 as the cathode demonstrates a remarkable specific discharge capacity of 169 mAh g−1 at 0.1 °C. The strategy of organic polymer-coated LLZTO provides the possibility of a green manufacturing process for preparing room-temperature sinter-free solid-state electrolytes, which shows significant cost-effectiveness.

African swine fever virus (ASFV) is one of the most complex viruses. ASFV is a serious threat to the global swine industry because no commercial vaccines against this virus are currently available except in Vietnam. Moreover, ASFV is highly stable in the environment and can survive in water, feed, and aerosols for a long time. ASFV is transmitted through the digestive and respiratory tract. Mucosal immunity is the first line of defense against ASFV. Saccharomyces cerevisiae (SC), which has been certified by the U.S. Food and Drug Administration and has a generally recognized as safe status in the food industry, was used for oral immunization in this study. ASFV antigens were effectively expressed in recombinant SC strains with high DNA copy numbers and stable growth though surface display technology and chromosome engineering (δ-integration). The recombinant SC strains containing eight ASFV antigens—KP177R, E183L, E199L, CP204L, E248R, EP402R, B602L, and B646L— induced strong humoral and mucosal immune responses in mice. There was no antigenic competition, and these antigens induced Th1 and Th2 cellular immune responses. Therefore, the oral immunization strategy using recombinant SC strains containing multiple ASFV antigens demonstrate potential for future testing in swine, including challenge studies to evaluate its efficacy as a vaccine against ASFV.

Abstract The operation of traditional aqueous-electrolyte zinc-ion batteries is adversely affected by the uncontrollable growth of zinc dendrites and the occurrence of side reactions. These problems can be avoided by the development of functional hydrogel electrolytes as replacements for aqueous electrolytes. However, the mechanism by which most hydrogel electrolytes inhibit the growth of zinc dendrites on a zinc anode has not been investigated in detail, and there is a lack of a large-scale recovery method for mainstream hydrogel electrolytes. In this paper, we describe the development of a recyclable and biodegradable hydrogel electrolyte based on natural biomaterials, namely chitosan and polyaspartic acid. The distinctive adsorptivity and inducibility of chitosan and polyaspartic acid in the hydrogel electrolyte triggers a double coupling network and an associated synergistic inhibition mechanism, thereby effectively inhibiting the side reactions on the zinc anode. In addition, this hydrogel electrolyte played a crucial role in an aqueous acid-based Zinc/MnO2 battery, by maintaining its interior two-electron redox reaction and inhibiting the formation of zinc dendrites. Furthermore, the sustainable biomass-based hydrogel electrolyte is biodegradable, and could be recovered from the Zinc/MnO2 battery for subsequent recycling.

Diabetes and depression are common comorbid conditions that impose a substantial health burden. Acupuncture may effectively improve symptoms in patients with diabetes and depression, but the underlying mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) may play a vital role in the effects of acupuncture on diabetes and depression comorbidity. This review summarizes the potential role of BDNF in acupuncture for diabetes and depression comorbidity. BDNF appears to exert its effects via the BDNF-TrkB-ERK-CREB signaling pathway. BDNF levels are reduced in diabetes and depression, and acupuncture may increase BDNF expression, improving symptoms and glycemic control. High-quality research is needed to validate the efficacy of acupuncture for diabetes and depression comorbidity. Randomized controlled trials and mechanistic studies should investigate the BDNF pathway and other potential mechanisms. Improved understanding of the links between diabetes, depression and acupuncture may enable targeted and individualized patient care. Earlier diagnosis and management of diabetes and depression comorbidity should also be a priority.

Abstract Chronic kidney disease affects approximately 14.3% of people worldwide. Tubulointerstitial fibrosis is the final stage of almost all progressive CKD. To date, the pathogenesis of renal fibrosis remains unclear, and there is a lack of effective treatments, leading to renal replacement therapy. Mitophagy is a type of selective autophagy that has been recognized as an important way to remove dysfunctional mitochondria and abrogate the excessive accumulation of mitochondrial-derived reactive oxygen species (ROS) to balance the function of cells. However, the role of mitophagy and its regulation in renal fibrosis need further examination. In this study, we showed that mitophagy was induced in renal tubular epithelial cells in renal fibrosis. After silencing BNIP3, mitophagy was abolished in vivo and in vitro, indicating the important effect of the BNIP3-dependent pathway on mitophagy. Furthermore, in unilateral ureteral obstruction (UUO) models and hypoxic conditions, the production of mitochondrial ROS, mitochondrial damage, activation of the NLRP3 inflammasome, and the levels of αSMA and TGFβ1 increased significantly following BNIP3 gene deletion or silencing. Following silencing BNIP3 and pretreatment with mitoTEMPO or MCC950, the protein levels of αSMA and TGFβ1 decreased significantly in HK-2 cells under hypoxic conditions. These findings demonstrated that HIF1α-BNIP3-mediated mitophagy played a protective role against hypoxia-induced renal epithelial cell injury and renal fibrosis by reducing mitochondrial ROS and inhibiting activation of the NLRP3 inflammasome.

As a popular energy storage equipment, lithium-ion batteries (LIBs) have many advantages, such as high energy density and long cycle life. At this stage, with the increasing demand for energy storage materials, the industrialization of batteries is facing new challenges such as enhancing efficiency, reducing energy consumption, and improving battery performance. In particular, the challenges mentioned above are particularly critical in advanced next-generation battery manufacturing. For batteries, the electrode processing process plays a crucial role in advancing lithium-ion battery technology and has a significant impact on battery energy density, manufacturing cost, and yield. Dry electrode technology is an emerging technology that has attracted extensive attention from both academia and the manufacturing industry due to its unique advantages and compatibility. This paper provides a detailed introduction to the development status and application examples of various dry electrode technologies. It discusses the latest advancements in commonly used binders for different dry processes and offers insights into future electrode manufacturing.

The preservation of biodiversity is crucial for maintaining ecological balance and promoting the harmonious development of mankind and nature. To formulate a biodiversity conservation plan for Guilin in China and accurately evaluate the impact of conservation measures on regional biodiversity, this study combined the InVEST model (v 3.7.0), the GeoSOS-FLUS model (v 2.3), and the landscape pattern index, analyzing the spatiotemporal changes in biodiversity from 2000 to 2020 in Guilin and simulating biodiversity under different development scenarios in 2040. The results showed the following: (1) The biodiversity index in Guilin displayed a declining trend, with the average annual value decreasing from 0.875 in 2000 to 0.870 in 2020. The area experiencing a reduction in biodiversity was primarily concentrated around the city. (2) The biodiversity level of each district and county had a large spatiotemporal difference, with the overall distribution characteristics of “higher in the northwest, southwest, and east, and lower in the northeast, southeast and central”. (3) The biodiversity hotspots were identified as priority areas for conservation; woodland and wetland were effectively protected, and the expansion of construction land and arable land was limited under the ecological protection scenario compared with the natural development scenario. (4) The annual average value of the biodiversity index of Guilin could reach 0.872 in 2040 after the adoption of ecological conservation measures, which is 0.013 higher than the natural development scenario. The results of this study can provide guidance for the construction of a national sustainable development model city and land use planning in Guilin, as well as a scientific reference for the creation of biodiversity conservation policies.

Type 2 diabetes (T2D) is the leading cause of diabetes worldwide and is increasing rapidly, especially in youth. It accounts for most diabetes deaths in adults ≥20 years old in the Americas, with type 2 diabetes responsible for most of the disease burden. The incidence and burden of type 2 diabetes in adolescents and young adults have risen in recent decades globally. Countries with lower socioeconomic status had the highest incidence and burden, and females generally had higher mortality and disease burden than males at ages

With the extensive integration of the Internet, social networks and the internet of things, the social internet of things has increasingly become a significant research issue. In the social internet of things application scenario, one of the greatest challenges is how to accurately recommend or match smart objects for users with massive resources. Although a variety of recommendation algorithms have been employed in this field, they ignore the massive text resources in the social internet of things, which can effectively improve the effect of recommendation. In this paper, a smart object recommendation approach named object recommendation based on topic learning and joint features is proposed. The proposed approach extracts and calculates topics and service relevant features of texts related to smart objects and introduces the “thing-thing” relationship information in the internet of things to improve the effect of recommendation. Experiments show that the proposed approach enables higher accuracy compared to the existing recommendation methods.

Parkinson's disease-related constipation (PDC) is commonly associated with impaired dopamine transmission and gastrointestinal dysfunction. Current pharmacological treatments have limited efficacy and potential side effects. Acupuncture has shown promise as an alternative or adjunct therapy by modulating the brain–gut axis, gastrointestinal hormones, and autonomic function. Preliminary randomized trials have shown that acupuncture significantly improves constipation symptoms, bowel movements, and comfort compared to sham or drug treatments and is well-tolerated. The mechanisms of action may involve regulating the gut microbiota and mucosal immunity to improve dysbiosis and gastrointestinal motility. However, more rigorous studies are required to optimize acupuncture protocols and determine long-term efficacy and safety. In summary, acupuncture shows promise as an adjunct therapy for PDC, but further research is needed to confirm its efficacy and safety.

Lithium-ion batteries (LIBs) have recently become popular for energy storage due to their high energy density, storage capacity, and long-term cycle life. Although binders make up only a small proportion of LIBs, they have become the key to promoting the transformation of the battery preparation process. Along with the development of binders, the battery manufacturing process has evolved from the conventional slurry-casting (SC) process to a more attractive solvent-free (SF) method. Compared with traditional LIBs manufacturing method, the SF method could dramatically reduce and increase the energy density due to the reduced preparation steps and enhanced electrode loading. Polytetrafluoroethylene (PTFE), as a typical binder, has played an important role in fabricating high-performance LIBs, particularly in regards to the SF technique. In this paper, the development history and application status of PTFE binder was introduced, and then its contributions and the inherent problems involved in the SF process were described and analyzed. Finally, the viewpoints concerning the future trends for PTFE-based SF manufacturing methods were also discussed. We hope this work can inspire future research concerning high-quality SF binders and assist in promoting the evolution of the SF manufacturing technology in regards to LIBs.

IntroductionThe bulb of Fritillaria hupehensis, a traditional cough and expectorant medicine, is usually harvested from June to September according to traditional cultivation experience, without practical scientific guidance. Although steroidal alkaloid metabolites have been identified in F. hupehensis, the dynamic changes in their levels during bulb development and their molecular regulatory mechanisms are poorly understood.MethodsIn this study, integrative analyses of the bulbus phenotype, bioactive chemical investigations, and metabolome and transcriptome profiles were performed to systematically explore the variations in steroidal alkaloid metabolite levels and identify the genes modulating their accumulation and the corresponding regulatory mechanisms.ResultsThe results showed that weight, size, and total alkaloid content of the regenerated bulbs reached a maximum at IM03 (post-withering stage, early July), whereas peiminine content reached a maximum at IM02 (withering stage, early June). There were no significant differences between IM02 and IM03, indicating that regenerated bulbs could be harvested appropriately in early June or July. Peiminine, peimine, tortifoline, hupehenine, korseveramine, delafrine, hericenone N-oxide, korseveridine, puqiedinone, pingbeinone, puqienine B, puqienine E, pingbeimine A, jervine, and ussuriedine levels were upregulated in IM02 and IM03, compared with IM01 (vigorous growth stage, early April). The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the accumulation of steroidal alkaloid metabolites mainly occurred prior to IM02. HMGR1, DXR, CAS1, CYP 90A1, and DET2 may play a positive role in peiminine, peimine, hupehenine, korseveramine, korseveridine, hericenone N-oxide, puqiedinone, delafrine, tortifoline, pingbeinone, puqienine B, puqienine E, pingbeimine A, jervine, and ussuriedine biosynthesis, whereas the downregulation of FPS1, SQE and 17-DHCR may lead to a reduction in peimisine levels. Weighted gene correlation network analysis showed that CYP 74A2-1, CYP 74A2-2, CYP 71A26-1, CYP 71A26-2, and CYP74A were negatively correlated with peiminine and pingbeimine A, whereas CYP R and CYP707A1 were positively correlated. . CYP 74A2-1 and CYP 74A2-2 may play a negative role in peimine and korseveridine biosynthesis, whereas CYP R plays a positive role. In addition, the highly expressed C2H2, HSF, AP2/ERF, HB, GRAS, C3H, NAC, MYB-related transcription factors (TFs), GARP-G2-like TFs, and WRKY may play positive roles in the accumulation of peiminine, peimine, korseveridine, and pingbeimine A.DiscussionThese results provide new insights into scientific harvesting of F. hupehensis.

In new-tier cities with rapid urbanization, the reorganization of urban spatial functions and the development of road networks have brought novel challenges to traffic congestion control. Urban land use patterns have a significant correlation with urban traffic congestion. However, whether and how land use patterns of cities close to the roads affect road congestion is less to be discussed. This article investigated the relationship between land use patterns close to the urban trunk road network and traffic congestion in new tier cities Xi’an, China. We adopted the DBSCAN algorithm to cluster POIs and use the mixed POI clusters to label the socio-economic functions of roads. We found the spatial heterogeneity of POIs on the trunk road network and identified the impacts of the scales and types of POI on road congestion based on the empirical analysis. Compared to the POIs as origin and destination of the trips, the POIs as stopover points of the trips cause significantly more road congestion. The POIs with bidirectional flows at entrances/exits are more likely to cause road congestion than the POIs with unidirectional flows. Moreover, the POIs with flexible traffic flows increase road congestion, while the POIs with predicted traffic flows have no statistically significant correlation with road congestion. The results help urban planners to plan the scale, type, and location of POIs close to roads and to optimize the socio-economic functions of roads and alleviate road congestion.

Most of the available divisible-load scheduling models assume that all servers in networked systems are idle before workloads arrive and that they can remain available online during workload computation. In fact, this assumption is not always valid. Different servers on networked systems may have heterogenous available times. If we ignore the availability constraints when dividing and distributing workloads among servers, some servers may not be able to start processing their assigned load fractions or deliver them on time. In view of this, we propose a new multi-installment scheduling model based on server availability time constraints. To solve this problem, we design an efficient heuristic algorithm consisting of a repair strategy and a local search strategy, by which an optimal load partitioning scheme is derived. The repair strategy guarantees time constraints, while the local search strategy achieves optimality. We evaluate the performance via rigorous simulation experiments and our results show that the proposed algorithm is suitable for solving large-scale scheduling problems employing heterogeneous servers with arbitrary available times. The proposed algorithm is shown to be superior to the existing algorithm in terms of achieving a shorter makespan of workloads.

Liquid ammonia is an ideal zero-carbon fuel for internal combustion engines. High-pressure injection is a key technology in organizing ammonia combustion. Characteristics of high-pressure liquid ammonia injection is lack of research. Spray behaviors are likely to change when a high-pressure diesel injector uses liquid ammonia as its fuel. This study uses high-speed imaging with a DBI method to investigate the liquid penetration, width, and spray tip velocity of high-pressure liquid ammonia injection up to 100 MPa. Non-flash and flash boiling conditions were included in the experimental conditions. Simulation was also used to evaluate the results. In non-flash boiling conditions, the Hiroyasu model provided better accuracy than the Siebers model. In flash boiling conditions, a phenomenon was found that liquid penetration and spray tip velocity were strongly suppressed in the initial stage of the injection process, this being the “spray resistance phenomenon”. The “spray resistance phenomenon” was observed when ambient pressure was below 0.7 MPa during 0–0.05 ms ASOI and was highly related to the superheated degree. The shape of near-nozzle sprays abruptly changed at 0.05 ms ASOI, indicating that strong cavitation inside the nozzle caused by needle lift effects is the key reason for the “spray resistance phenomenon”.

A major challenge in many machine learning tasks is that the model expressive power depends on model size. Low-rank tensor methods are an efficient tool for handling the curse of dimensionality in many large-scale machine learning models. The major challenges in training a tensor learning model include how to process the high-volume data, how to determine the tensor rank automatically, and how to estimate the uncertainty of the results. While existing tensor learning focuses on a specific task, this paper proposes a generic Bayesian framework that can be employed to solve a broad class of tensor learning problems such as tensor completion, tensor regression, and tensorized neural networks. We develop a low-rank tensor prior for automatic rank determination in nonlinear problems. Our method is implemented with both stochastic gradient Hamiltonian Monte Carlo (SGHMC) and Stein Variational Gradient Descent (SVGD). We compare the automatic rank determination and uncertainty quantification of these two solvers. We demonstrate that our proposed method can determine the tensor rank automatically and can quantify the uncertainty of the obtained results. We validate our framework on tensor completion tasks and tensorized neural network training tasks.

We demonstrate a chip-scale germanium-silicon optical phased array (OPA) fabricated on a CMOS-compatible platform capable of 2D beam steering in the mid-infrared wavelength range. The OPA included a specially designed grating emitter waveguide array with uniform emission intensity along the mm-length waveguide propagation to realize very sharp instantaneous field-of-view (IFOV) and wide beam-steering total-field-of-view (TFOV). The experimental results indicated lateral beam-steering TFOV up to 12.7° by phase-tuning the waveguide array and longitudinal TFOV up to 12° by wavelength tuning. The 3-dB beam divergence is 3.08° × 0.18°. The demonstrated OPA architecture can employ wafer-scale fabrication and integration while supporting sensing and imaging applications in the mid-infrared spectral range.

Background Immediately placed implants with immediate provisionalization have become attractive options for patients and clinicians. However, there is no agreement on the esthetic advantages of immediately placed implants with immediate provisionalization. The aim of this systematic review and meta-analysis will be to assess the effect of immediate provisionalization on the clinical esthetic outcomes of immediately placed implants in a single-tooth implant of the esthetic area. Methods An electronic search of MEDLINE/PubMed, EMBASE, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine (CBM), Wan Fang Database, China National Knowledge Infrastructure Database (CNKI), and VIP Science Technology Periodical Database will be performed. The search will be carried out in the databases for articles published until May 2021. Two researchers will independently perform the literature selection, data extraction and quality assessment. Only randomized controlled trials (RCTs) reporting on the impact of immediate provisionalization on the clinical esthetic outcomes of implants immediately placed in a single-tooth implant of the aesthetic area will be included. The primary outcome of this study will be the esthetic outcome assessed by the objective index and patient satisfaction. The survival rate of implants and restorations and the changes in mucosa and bone around implants will also be analyzed. The included studies will be analyzed by Review Manager 5.3, and a meta-analysis will be performed. Results The study will evaluate the clinical esthetic outcomes of immediately placed implants with and without immediate provisionalization in single-tooth implants of the esthetic area. The results will provide clinicians with a better treatment approach in their application. Conclusion This systematic review and meta-analysis will provide more reliable, evidence-based data for the impact of immediate provisionalization on the clinical esthetic outcomes of immediately placed implants, which may or may not be beneficial. Registration number PROSPERO registration number: CRD42021221669.

Grape seed procyanidin extract (GSPE) can modulate intestinal dysfunction, however; the mechanism needs to be clarified. This study aims at investigating the beneficial effect of GSPE on intestinal epithelial integrity and its regulatory mechanism. The results showed that consumption of high-fat (HF) diet for 13 weeks increased intestinal permeability. GSPE (200 mg/kg·bw) treatment reduced the concentration of lipopolysaccharide (LPS) in the circulatory system. The expression of tight junction proteins increased in GSPE-treated rats. Moreover, GSPE treatment inhibited the expression of pro-inflammatory mediators. The flow cytometry results revealed that GSPE treatment significantly increased the proportion of CD4+ CD25+ Foxp3+ Tregs in gut-associated lymphoid tissue. GSPE modulated the composition of the gut microbiota and Spearman's correlation analysis revealed that the genera Anaerotruncus, Blautia, Oscillibacter, and Ruminococcaceae_UCG-004 were related to intestinal permeability indices. In conclusion, GSPE ameliorated intestinal barrier dysfunction in HF diet-fed rats, probably via the regulation of intestinal immune balance and intestinal microbiota.

Models of the consensus of the individual state in social systems have been the subject of recent research studies in the physics literature. We investigate how network structures coevolve with the individual state under the framework of social identity theory. Also, we propose an adaptive network model to achieve state consensus or local structural adjustment of individuals by evaluating the homogeneity among them. Specifically, the similarity threshold significantly affects the evolution of the network with different initial conditions, and thus there emerges obvious community structure and polarization. More importantly, there exists a critical point of phase transition, at which the network may evolve into a significant community structure and state-consistent group.

Skyline query retrieves a set of skyline points which are not dominated by any other point and has attracted wide attention in database community. Recently, an important variant G-Skyline is developed. It aims to return optimal groups of points. However, when data dimensionality is high, G-Skyline result has too many groups, which makes that users cannot determine which groups are satisfactory. To find less but more representative groups of points, in this paper, we propose a novel concept of $k$ -dominant G-Skyline, which first adopts $k$ -dominance to retrieve more representative points and then computes the groups not $k$ -dominated by others. In addition, we present a two-phase algorithm to efficiently compute $k$ -dominant G-Skyline groups. In the first phase, we construct a $lk$ DG structure while pruning the points never included in any $k$ -dominant G-Skyline group as much as possible. In the second phase, using $lk$ DG, we propose two efficient $k$ -dominant G-Skyline searching methods SM-P and SM-G, which generate new candidate groups from single points and ancestor groups, respectively. Our experimental results indicate that our proposed algorithms are more efficient than the baseline methods on real and synthetic data sets.

Enterotoxigenic Escherichia coli (ETEC) are opportunistic pathogens that colonize the small intestine, produce enterotoxins and induce diarrhea. Some aquaporins (AQPs), such as AQP3 and AQP8, have been reported to participate in diarrhea by decreasing cellular influx in the gastrointestinal (GI) tract. AQP4 is another important water channel in the GI tract, but its role in ETEC-induced diarrhea has not been reported. Here, we demonstrated the potential roles of AQP4 in ETEC-induced diarrhea. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting showed that AQP4 was expressed in the mouse ileum, but not in the duodenum or jejunum while immunohistochemical staining showed that AQP4 localized to the basolateral membrane of ileum epithelial cells. Using an ETEC-induced mice diarrhea model, we demonstrated that both AQP4 mRNA level and the AQP4 protein level in the ileum decreased gradually over a time course of 7 days. These results suggest that AQP4 plays a role in the pathogenesis of ETEC-induced diarrhea by mediating water transport.

This meta-analysis aimed to examine the effects of plyometric training on physical fitness attributes in handball players. A systematic literature search across PubMed, SCOPUS, SPORTDiscus, and Web of Science identified 20 studies with 563 players. Plyometric training showed significant medium-to-large effects on various attributes: countermovement jump with arms (ES = 1.84), countermovement jump (ES = 1.33), squat jump (ES = 1.17), and horizontal jump (ES = 0.83), ≤ 10-m linear sprint time (ES = -1.12), > 10-m linear sprint time (ES = -1.46), repeated sprint ability with change-of-direction time (ES = -1.53), agility (ES = -1.60), maximal strength (ES = 0.52), and force--velocity (muscle power) (ES = 1.13). No significant impact on balance was found. Subgroup analysis indicated more pronounced agility improvements in players ≤ 66.6 kg compared to > 66.6 kg (ES = -1.93 vs. -0.23, p = 0.014). Additionally, greater improvements were observed in linear sprint and repeat sprint ability when comparing training durations of > 8 weeks with those ≤ 8 weeks (ES = -2.30 to -2.89 vs. ES = -0.92 to -0.97). In conclusion, plyometric training effectively improves various physical fitness attributes, including jump performance, linear sprint ability, maximal strength, muscle power and agility. [ABSTRACT FROM AUTHOR]