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Background: Functional disability, defined as acquired difficulty in performing basic daily tasks or more complex tasks needed for independent living. Functional assessment among community dwelling elderly is critical due to the changes taking place during the normal aging process, acute illness, worsening chronic illness, and hospitalization which compromises their performances necessary to live independently. Measuring their functional ability can provide objective data to assist with targeting individualized care plan for older adults being the highest consumers of medications due to greater burden of medical conditions in addition to being vulnerable to the effects of medications. It is crucial for the pharmacists to be aware of the geriatric functional disability as pharmacies are often the first point-of-care this elderly group may encounter in community settings. Methods: This study was conducted to estimate the prevalence of functional disability and the common difficulties in the daily task performance among elderly from a state in the Northern region of Malaysia. Besides, the differences in terms of functional disability in both genders were also explored. Among a total of 266 elderly participants. Results: Around 42 % was estimated to face at least one difficulty with Activities of Daily Living while more than half, 57 %, had at least one difficulty with Instrumental Activities of Daily Living. The most common difficulties reported with Activities of Daily Living and Instrumental Activities of Daily Living were transferring (22 %) and transportation (33 %), respectively. Conclusion: In order to deliver effective pharmaceutical care plan emphatically, both senior-friendly pharmacy curricula and pharmacy settings are imperative to address the most common difficulties faced by this vulnerable group.

Underground coal gasification (UCG) as an alternative coal mining technology is attracting much attention. However, due to the high experimental cost of UCG, the evolution mechanism of coal seam should be deeply explored prior to the implement of experiments. By virtue of the great computational power of computers, the computational fluid dynamics (CFD) is able to simulate the production process of UCG at a relatively lower cost. The in-situ ignition and combustion of deep coal seam heated by 1 000 K flue gas is simulated and the changes of temperature, molar O2 fraction and porosity are analyzed by the CFD software, Fluent, developed by Ansys cor-poration. It is elucidated that pumping 1 000 K flue gas for 500 s is inadequate for coal seam ignition, while 1 000 s heating has been enough for coal seam ignition. On the internal surface of coal seam, the high temperature is accumulated in the 0−0.6 m coal seam near inlet. The maximum temperature before ignition is below inlet temperature of heating flue gas, 1 000 K, while the maximum temperature after ignition exceeds 1 000 K and reaches up to 1 250 K. Almost all O2 is consumed in the high-temperature zone, while less than 2% molar O2 fraction arrives at the internal surface of coal seam in other lower-temperature zones. The porosity rapidly increases in high-temperature zone and at 1000 s the porosity in the part of coal seam reaches up to 0.9. In the interior of coal seam, the thicker the coal seam is, the lower the temperature rises. The maximum temperature on 7 cm line is only 500 K at 1 000 s and 2 000 s, much lower than that on the internal surface of coal seam when it is heated for the same time. During 2 000 s ignition, little O2 penetrates 7 cm and 14 cm coal seam and the porosities of interior coal seam are all below 0.4. The low porosities are attributed to the low temperature and low molar O2 fraction. The simulation on temperature, molar O2 fraction and porosity may provide a reference for how to promote the reaction in the interior of coal seam.

Abstract Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also represents the position of a conspecific performing a spatial task. However, whether this representation is allocentric, egocentric or mixed is less clear. In this study we investigated the representation of others during free behavior and in a task where female mice learned to follow a conspecific for a reward. We found that most cells represent the position of others relative to self-position (social-vector cells) rather than to the environment, with a prevalence of purely egocentric coding modulated by context and mouse identity. Learning of a pursuit task improved the tuning of social-vector cells, but their number remained invariant. Collectively, our results suggest that the hippocampus flexibly codes the position of others in multiple coordinate systems, albeit favoring the self as a reference point.

Precisely predicting natural gas prices (NGPs) is important because it can provide the necessary decision-making basis for energy scheduling, planning and control. However, NGPs are affected by many factors and exhibit the characteristics of nonlinearity and randomness, which makes accurate predictions challenging. Therefore, in this paper, the information gain of multisource data and the global optimization ability of the gray wolf algorithm are used to build a multifactor-driven NGP hybrid forecasting model to improve the prediction performance. First, the emotional tendency and readability of news text are extracted and calculated by using VADER and textstat tools, respectively. Then the network search index is filtered and integrated by using the correlation coefficient method and the CRITIC method to form alternative variables of multisource data (news and search index). Second, the gray wolf optimization algorithm is used to find and determine the best key parameter group in long short-term memory model. Finally, the spot price of natural gas in Henry Hub from March 1, 2012 to February 28, 2022 is selected as the prediction object, and multi-scenario numerical experiments are carried out to verify the effectiveness of the proposed model. The ablation experiment results show that the information gain brought by multisource data can effectively improve the prediction effect of NGPs. Furthermore, the proposed model has the best prediction performance in different scenarios and can be regarded as a promising prediction tool.

Currently, the drugs used in clinical to treat psoriasis mainly broadly suppress cellular immunity. However, these drugs can only provide temporary and partial symptom relief, they do not cure the condition and may lead to recurrence or even serious toxic side effects. In this study, we describe the discovery of a novel potent CDK8 inhibitor as a treatment for psoriasis. Through structure-based design, compound 46 was identified as the most promising candidate, exhibiting a strong inhibitory effect on CDK8 (IC50 value of 57 nM) along with favourable inhibition against NF-κB. Additionally, it demonstrated a positive effect in an in vitro psoriasis model induced by TNF-α. Furthermore, this compound enhanced the thermal stability of CDK8 and exerted evident effects on the biological function of CDK8, and it had favourable selectivity across the CDK family and tyrosine kinase. This compound showed no obvious inhibitory effect on CYP450 enzyme. Further studies confirmed that compound 46 exhibited therapeutic effect on IMQ-induced psoriasis, alleviated the inflammatory response in mice, and enhanced the expression of Foxp3 and IL-10 in the dorsal skin in vivo. This discovery provides a new strategy for developing selective CDK8 inhibitors with anti-inflammatory activity for the treatment of psoriasis.

Background: HbA1c test is the most-ordered laboratory test in public primary care clinics, accounting for 17% of laboratory services. In recent years, there has been growing adoption of self-service technology in taking clinical measurements. However, there are currently no on-site self-testing HbA1c facilities. This study assessed patients’ acceptability and ability to perform self-testing of HbA1c levels and the feasibility of implementation in primary care setting. Methods: A total of 30 eligible diabetic patients were recruited in Tampines Polyclinic. Participants were shown a demonstration video before self-testing with a Point-of-Care HbA1c analyzer and completed a questionnaire after self-testing. The usability of the system was assessed using System Usability Scale (SUS). Acceptance and ability were assessed using either a five or six point-Likert Scale for the 7-step procedure. Fisher’s exact test was used to test for association with SUS score. Results: The study population comprises mainly males (60.0%), Chinese (50.0%), had highest qualification of secondary education and beyond (80.0%), with a mean age of 61.4 ± 8.3 years. The mean SUS score was 66.5 ± 13.3 and the average time taken to complete the HbA1c self-testing was 11.8 ± 4.5 min. No significant association was observed between demographics and SUS score. Although 40.0% of participants experienced some difficulty in inserting the cartridge into the analyzer, all were able to understand and follow the video and were willing to perform self-testing in the future. Conclusion: There is high level of acceptance and ability among diabetic patients to adopt HbA1c self-testing. It is feasible for use in primary care.

ObjectiveThe aim of this study was to identify the molecular subtypes of breast cancer based on chromatin regulator-related genes.MethodsThe RNA sequencing data of The Cancer Genome Atlas–Breast Cancer cohort were obtained from the official website, while the single-cell data were downloaded from the Gene Expression Omnibus database (GSE176078). Validation was performed using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Furthermore, the immune characteristics, tumor stemness, heterogeneity, and clinical characteristics of these molecular subtypes were analyzed. The correlation between chromatin regulators and chemotherapy resistance was examined in vitro using the quantitative real-time polymerase chain reaction (qRT-PCR) and Cell Counting Kit-8 (CCK8) assays.ResultsThis study identified three stable molecular subtypes with different prognostic and pathological features. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein–protein interaction analyses revealed that the differentially expressed genes were associated with disease processes, such as mitotic nuclear division, chromosome segregation, condensed chromosome, and specific chromosome region. The T stage and subtypes were correlated with the clinical features. Tumor heterogeneity (mutant-allele tumor heterogeneity, tumor mutational burden, purity, and homologous recombination deficiency) and tumor stemness (RNA expression-based stemness score, epigenetically regulated RNA expression-based stemness score, DNA methylation-based stemness score, and epigenetically regulated DNA methylation-based stemness score) significantly varied between the three subtypes. Furthermore, Western blotting, qRT-PCR, and CCK8 assays demonstrated that the expression of ASCL1 was positively correlated with chemotherapy resistance in breast cancer.ConclusionThis study identified the subtypes of breast cancer based on chromatin regulators and analyzed their clinical features, gene mutation status, immunophenotype, and drug sensitivity. The results of this study provide effective strategies for assessing clinical prognosis and developing personalized treatment strategies.

ObjectiveAccording to the World Alzheimer’s Disease Report in 2015,there were 9.9 million new cases of dementia in the world every year. At present, the number of patients suffering from dementia in China has exceeded 8 million, and it may exceed 26 million by 2040.Mild cognitive impairment (MCI) refers to the pathological state of pre-dementia with the manifestation of the progressive decline of memory or other cognitive functions but without decline of activities of daily life. It is particularly important to prevent or prolong the development of MCI into dementia. Research showing effects of rhythmic auditory stimulation based-movement training(RASMT) interventions on cognitive function is also emerging. Therefore, the present meta-analysis briefly summarize findings regarding the impacts of RASMT programs on cognitive impairment.MethodsData from Pubmed, Embase, and Cochrane Library were utilized. The impact of RASMT on cognitive functions was evaluated using indicators such as overall cognitive status, memory, attention, and executive functions. The REVMAN5.3 software was employed to analyze bias risks integrated into the study and the meta-analysis results for each indicator.ResultsA total of 1,596 studies were retrieved, of which 1,385 non-randomized controlled studies and 48 repetitive studies were excluded. After reviewing titles and abstracts of the remaining 163 articles, 133 irrelevant studies were excluded, 30 studies were downloaded and read the full text. Among 30 articles, 18 articles that did not meet the inclusion criteria were excluded, the other 12 studies were included in this meta-analysis. Utilizing the Cochrane Collaborative Network Bias Risk Assessment Scale, it was found that 11 studies explained the method of random sequence generation, nine studies did not describe allocation concealment, four were single-blinded to all researchers, and eight reported single-blinding in the evaluation of experimental results. In the meta-analysis, the main outcomes showed statistically significant differences in overall cognitive status [MD = 1.19, 95%CI (0.09, 2.29), (p

As one of the most vital ecological regions in China, the well-being of the Inner Mongolia section of the Yellow River Basin directly hinges upon comprehending the variations in its ecosystem. The current research puts emphasis on the analysis of single-factor ecological indicators within the Mongolian section of the Yellow River and lacks summarization and analysis regarding the overall state of the ecosystem within the Mongolian section of the Yellow River. This study, using methods such as remote sensing interpretation and model simulation, combined with ground surveys, analyzes the macrostructure, quality status, service functions, and driving factors of the ecosystem in the Inner Mongolia section of the Yellow River Basin from 2000 to 2020. The results indicate that (1) in 2020, the ecosystem structure in the Inner Mongolia section of the Yellow River Basin was predominantly composed of forest, grassland, and other types of systems. (2) From 2000 to 2020, the Normalized Difference Vegetation Index (NDVI), Fractional Vegetation Cover (FVC), and net primary productivity (NPP) all showed increasing trends in the Inner Mongolia section of the Yellow River Basin, with NPP showing a slightly greater increase compared to the NDVI and FVC. (3) Over the past two decades, the overall rate of decrease in the wind erosion modulus per unit area was 1.675 t hm−2. (4) An analysis of the drivers of ecosystem changes revealed that while climate change has exerted an influence, human activities have likewise had a substantial effect on the ecosystem over the past 20 years. This study contributes to a comprehensive understanding of the current status and changes in the ecosystem, providing a decision-making basis for subsequent ecological protection and management projects.

In September 2020, the Federal Energy Regulatory Commission (FERC) released Order 2222, which opens wholesale markets to small-capacity distributed energy resources (DERs), recognizing their potential in improving operational efficiency by providing bulk grid services. Therefore, a co-simulation capability that can connect transmission and distribution (T&D) simulations and evaluate the impacts of DER provision of bulk grid services is needed. In this paper, we present a new integrated T&D co-simulation platform that incorporates T&D system simulators, DER aggregator/group strategies, and a co-simulation coordinator. Industry-standard communication protocols are employed to mimic real-world conditions. Secondary frequency regulation is selected as the representative bulk grid service, and we simulate the responses of DERs to the frequency regulation signals. The simulation results for a solar-rich distribution feeder in Colorado, USA, demonstrate how the T&D co-simulation setup is used to evaluate the contributions of DERs to minimize the bulk grid frequency deviation.

Summary: Klebsiella pneumoniae (Kp) infection is an important healthcare concern. The ST258 classical (c)Kp strain is dominant in hospital-acquired infections in North America and Europe, while ST23 hypervirulent (hv)Kp prevails in community-acquired infections in Asia. This study aimed to develop symptomatic mucosal infection models in mice that mirror natural infections in humans to gain a deeper understanding of Kp mucosal pathogenesis. We showed that cKp replicates in the nasal cavity instead of the lungs, and this early infection event is crucial for the establishment of chronic colonization in the cecum and colon. In contrast, hvKp replicates directly in the lungs to lethal bacterial load, and early infection of esophagus supported downstream transient colonization in the ileum and cecum. Here, we have developed an in vivo model that illuminates how differences in Kp tropism are responsible for virulence and disease phenotype in cKp and hvKp, providing the basis for further mechanistic study.

The extraction of roadways from remote sensing imagery constitutes a pivotal task, with far-reaching implications across diverse domains such as urban planning, management of transportation systems, emergency response initiatives, and environmental monitoring endeavors. Satellite images captured during daytime have customarily served as the primary resource for this extraction process. However, the emergence of Nighttime Light (NTL) remote sensing data introduces an innovative dimension to this arena. The exploration of NTL data for road extraction remains in its nascent stage, and this study seeks to bridge this gap. We present a refined U-Net model (CA U-Net) integrated with Cross-Attention Mechanisms, meticulously designed to extract roads from Yangwang-1 NTL images. This model incorporates several enhancements, thereby improving its proficiency in identifying and delineating road networks. Through extensive experimentation conducted in the urban landscape of Wenzhou City, the model delivers highly accurate results, achieving an F1 score of 84.46%. These outcomes significantly surpass the performance benchmarks set by Support Vector Machines (SVM) and the Optimal Threshold (OT) method. This promising development paves the way towards maximizing the utility of NTL data for comprehensive mapping and analysis of road networks. Furthermore, the findings underscore the potential of utilizing Yangwang-1 data as a reliable source for road extraction and reaffirm the viability of deploying deep learning frameworks for road extraction tasks utilizing NTL data.

Abstract Background With its high nutritional value and productivity, Italian ryegrass as a biomass feedstock constantly supplies rumen degradable nitrogen and digestible fiber to ruminants. However, biofuel production is easily reduced during ensiling due to the high-moisture content of Italian ryegrass, leading to economic losses. Lactic acid bacteria inoculants could improve lignocellulosic degradation and fermentation quality and decrease dry matter loss during the bioprocessing of silage. Therefore, this study analyzed the effects of Lactobacillus buchneri TSy1-3 (HE), Lactobacillus rhamnosus BDy3-10 (HO), and the combination of HE and HO (M) on fermentation quality, bacterial community and metabolome in high-moisture Italian ryegrass silage during ensiling. Results The results showed that the pH value was significantly lower in the HO groups than in the other treatments at the end of ensiling, and the dry matter and acetic acid contents were significantly higher in the HO group than in the other inoculated groups. All inoculants decreased the diversity of the bacterial community and significantly increased the relative abundance of Lactobacillus. Inoculation with HO significantly improved the concentrations of organic acids, dipeptides, ferulic acid, apigenin, and laricitrin. Compared with Lactobacillus buchneri TSy1-3 (HE), HO significantly upregulated the flavonoid compounds in the flavone and flavonol biosynthesis pathway. Conclusions Overall, these findings suggest that inoculation with HO was beneficial for the development of Italian ryegrass as a biomass feedstock, improving fermentation quality, accelerating changes in bacterial community composition and increasing biofunctional metabolites in high-moisture Italian ryegrass silage.

Abstract Background Cardiometabolic disease is a clinical syndrome characterized by multiple metabolic disorders, with atherosclerosis as the core and cardiovascular and cerebrovascular events as the outcome. Drug research and development (R&D) in cardiometabolic diseases has grown rapidly worldwide. However, the development of cardiometabolic drug clinical trials in China remains unclear. This study aims to depict the changing landscape of drug clinical trials for cardiometabolic diseases in China during 2009–2021. Methods The detailed information of drug trials on cardiometabolic diseases registered in the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform was collected between January 1, 2009, and July 1, 2021. The landscape of cardiometabolic drug clinical trials was analyzed by the characteristics, time trends, indications, pharmacological mechanisms, and geographical distribution. Results A total of 2466 drug clinical trials on cardiometabolic diseases were extracted and analyzed. The annual number of drug trials increased rapidly in the past twelve years. Among all the trials, the bioequivalence trials (1428; 58.3%) accounted for the largest proportion, followed by phase I (555; 22.5%), phase III (278; 11.3%), phase II (169; 6.9%), and phase IV (26; 1.1%). Of 2466 trials, 2133 (86.5%) trials were monomer drugs, only 236 (9.6%) trials were polypills and 97 (3.9%) were traditional Chinese medicine (TCM) compounds. In terms of pharmacological mechanisms, the number of trials in dihydropyridine (DHP) calcium antagonists 321 (11.9%) ranked first, while trials in angiotensin receptor blocker (ARB) 289 (10.7%) and dipeptidyl peptidase-4 (DPP-4) inhibitor 205 (7.6%) ranked second and third place respectively. Of 236 chemical polypills trials, 23 (9.7%) polypills were the combination of DHP calcium antagonists and statins, while others were the combination of two same pharmacological effect agents. As for the geographical distribution of leading units, 36 trials were led by principal investigators (PI) units from Beijing, followed by Jiangsu (n = 29), Shanghai (n = 19), Guangdong (n = 19), and Hunan (n = 19), showing an uneven regional distribution. Conclusions Great progress has been made in drug clinical trials on cardiometabolic diseases, especially in antihypertensive agents, hypoglycemic agents, and hypolipidemic agents. However, the insufficient innovation of first-in-class drugs and polypills should be carefully considered by all stakeholders in drug trials.

Summary: Background: Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse. Methods: A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). Findings: A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates [XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%)] (p

Data pricing, which aids in articulating the worth and advantages of data and encourages its opening, sharing, and circulation, is an indispensable component of data trading. Studies pertinent to the topic of data pricing are continuously developing. To undertake a thorough analysis of the literature in data pricing, we use bibliometric and statistical methods for the first time. The 373 data pricing publications from 1990 to 2023 are the study's research object. We mainly analyze the external characteristics, keyword co-occurrence and co-citation networks of data pricing. We find that data pricing has been progressing fairly quickly during the last decade. Two basic approaches have been used by researchers to study how to price various data objects: one is based on economics theory, and the other on computer science algorithms. We provide an in-depth study of the overall evolution of data pricing and give the future directions of data pricing.

Paracrystalline state is still challenging to reach in alloy systems in a controlled manner. Here, the authors present an atomic-level tailoring route to create paracrystalline Zr-Nb-Hf-Ta-Mo high-entropy alloy through local amorphization induced by atomic-level Pt with negative mixing enthalpy.

This study investigates corrosion resistance and corrosion interface characteristics of novel Cr-alloyed steel rebar in mortar using electrochemical measurements, X-ray computed tomography (X-CT) scanning, and X-ray photoelectron spectroscope (XPS) analysis. Impressed constant current corrosion (ICCC) test was performed on alloyed steel rebar-mortar (ASRM) sample and carbon-steel rebar-mortar (CSRM) sample in a chloride-contaminated environment. After 5 days of ICCC test, alloyed steel rebar suffered a certain degree of localized corrosion with limited corrosion product, while the carbon-steel rebar presented severe general corrosion. Electrochemical tests demonstrated that the ASRM sample exhibited more than ten times in Rct value of the electrochemical impedance spectroscopy test and only about 0.46% in corrosion current density of the potentiodynamic polarization test compared to the CSRM sample. The above results revealed the excellent passivation performance and corrosion resistance of the ASRM sample, which is attributed to the formation of the stable composite passive film containing Cr/Fe oxides and hydroxides.

Abstract Objective Despite the high HIV associated burden, Mozambique lacks data on HIV counselling and testing (HCT) costs. To help guide national HIV/AIDS programs, we estimated the cost per test for voluntary counselling and testing (VCT) from the patient’s perspective and the costs per person tested and per HIV-positive individual linked to care to the healthcare provider for VCT, provider-initiated counselling and testing (PICT) and home-based testing (HBT). We also assessed the cost-effectiveness of these strategies for linking patients to care. Methods Data from a cohort study conducted in the Manhiça District were used to derive costs and linkage-to-care outcomes of the three HCT strategies. A decision tree was used to model HCT costs according to the likelihood of HCT linking individuals to care and to obtain the incremental cost-effectiveness ratios (ICERs) of PICT and HBT with VCT as the comparator. Sensitivity analyses were performed to assess robustness of base-case findings. Findings Based on costs and valuations in 2015, average and median VCT costs to the patient per individual tested were US$1.34 and US$1.08, respectively. Costs per individual tested were greatest for HBT (US$11.07), followed by VCT (US$7.79), and PICT (US$7.14). The costs per HIV-positive individual linked to care followed a similar trend. PICT was not cost-effective in comparison with VCT at a willingness-to-accept threshold of US$4.53, but only marginally given a corresponding base-case ICER of US$4.15, while HBT was dominated, with higher costs and lower impact than VCT. Base-case results for the comparison between PICT and VCT presented great uncertainty, whereas findings for HBT were robust. Conclusion PICT and VCT are likely equally cost-effective in Manhiça. We recommend that VCT be offered as the predominant HCT strategy in Mozambique, but expansion of PICT could be considered in limited-resource areas. HBT without facilitated linkage or reduced costs is unlikely to be cost-effective.

Silage can be contaminated with mycotoxins and accidental fungi after aerobic exposure. The study assessed the effects of bunker silos (BS), round bales (RB), and silage bags (SB) on the nutritional characteristics, fermentation quality, aerobic stability, mycotoxin levels and microbial communities of whole-plant corn silage (WPCS). After 90 days of fermentation, silages were opened and sampled at 0, 1, 3, 5, 7, and 9 days of exposure. SB group conserved higher lactic acid and dry matter contents and a lower pH value than other groups after 9 days of exposure (p

Diabetic kidney disease is a common complication of diabetes and remains the primary cause of end-stage kidney disease in the general population. Schisandrin B (Sch B) is an active ingredient in Schisandra chinensis. Our study illustrates that Sch B can mitigate renal tubular cell (RTC) epithelial–mesenchymal transition (EMT) and mitochondrial dysfunction in db/db mice, accompanied by the downregulation of TGF-β1 and the upregulation of PGC-1α. Similarly, Sch B demonstrated a protective effect by reducing the expression of TGF-β1, α-SMA, fibronectin, and Col I, meanwhile enhancing the expression of E-cadherin in human RTCs (HK2 cells) stimulated with high glucose. Moreover, under high glucose conditions, Sch B effectively increased mitochondrial membrane potential, lowered ROS production, and increased the ATP content in HK2 cells, accompanied by the upregulation of PGC-1α, TFAM, MFN1, and MFN2. Mechanistically, the RNA-seq results showed a significant increase in KCP mRNA levels in HK2 cells treated with Sch B in a high glucose culture. The influence of Sch B on KCP mRNA levels was confirmed by real-time PCR in high glucose-treated HK2 cells. Depletion of the KCP gene reversed the impact of Sch B on TGF-β1 and PGC-1α in HK2 cells with high glucose level exposure, whereas overexpression of the KCP gene blocked EMT and mitochondrial dysfunction. Furthermore, the PI3K/Akt pathway was inhibited and the AMPK pathway was activated in HK2 cells exposed to a high concentration of glucose after the Sch B treatment. Treatment with the PI3K/Akt pathway agonist insulin and the AMPK pathway antagonist compound C attenuated the Sch B-induced KCP expression in HK2 cells exposed to a high level of glucose. Finally, molecular autodock experiments illustrated that Sch B could bind to Akt and AMPK. In summary, our findings suggested that Sch B could alleviate RTC EMT and mitochondrial dysfunction by upregulating KCP via inhibiting the Akt pathway and activating the AMPK pathway in DKD.

Abstract Lithium‐thiophosphate‐based all‐solid‐state batteries (ASSBs) are increasingly attracting attention for high‐density electrochemical energy storage. In this work, the cycling performance of single and polycrystalline forms of LiNixCoyMnzO2 (NCM, with ≥83% Ni content) cathode active materials in ASSB cells with an Li4Ti5O12 composite anode is explored, and the advantages and disadvantages of both morphologies are discussed. The virtual lack of grain boundaries in the quasi‐single‐crystalline material is found to contribute to improved stability by eliminating the tendency of Ni‐rich NCM particles to crack during cycling, due to volume differences between the lithiated and delithiated phases. Although the higher crack resistance mitigates effects of chemical oxidation of the lithium thiophosphate solid electrolyte, the cells suffer from electrochemical side reactions occurring at the cathode interfaces. However, coating the single‐crystal particles with a protective LiNbO3 overlayer helps to stabilize the interface between cathode active material and solid electrolyte, leading to a capacity retention of 93% after 200 cycles (with qdis ≈ 160 mAh gNCM−1 or 1.7 mAh cm−2 at C/5 rate and 45 °C). Overall, this work highlights the importance of addressing electro‐chemo‐mechanical phenomena in ASSB electrodes.

IntroductionAutologous chondrocyte implantation (ACI) is a crucial method for the treatment of defects in articular cartilage. However, the extant methods for the preparation of autologous chondrocyte patch are relatively complicated and money-consuming. Therefore, an efficient, reliable, easy-to-follow, and cost-effective technique is needed to overcome constraints. This case report aims to introduce an autologous chondrocyte patch fabrication technique to repair knee joint cartilage defects and report our typical cases with a 2-year follow-up.Case presentationWe described four cases in which patients complained of knee joint pain. According to radiological examination, the patients were diagnosed as knee joint cartilage defect. Arthroscopy and autologous chondrocyte patch implantation were performed as well as a 2-year follow up of patients. The autologous chondrocyte patch for knee joint cartilage repair was fabricated using a “sandwich” technique. The preoperative and postoperative knee function was evaluated by four subjective evaluation systems. MRI was performed for all patients to achieve more intuitionistic observation of the postoperative radiological changes of defect sites. The quality of repaired tissue was evaluated by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART). Postoperative follow-up showed improvement in clinical and MOCART scores for all patients. However, one patient complained of knee joint pain after walking for a long time or recreational activities from 12- to 18-month postoperatively. The location of pain for this patient was not in accordance with the location of cartilage defect.ConclusionThe patients undergoing autologous chondrocyte patch implantation demonstrated clinical improvement and good quality of repaired tissue postoperatively. The procedure is an efficient and cost-effective treatment for knee joint cartilage defect in this report. In addition, patients with osteoarthritis carry the risk of a poor outcome after the procedure, and whether to have a procedure should be considered carefully.

The purpose of this study was to investigate the effects of inoculation with two lactic acid bacteria (LAB) strains (Lacticaseibacillus rhamnosus and Lentilactobacillus buchneri) and the addition of four corn flour proportions (0, 3, 6, and 9%) in different treatments, on the composition and function of the bacterial community in whole-plant paper mulberry silage. The different treatments promoted Lactiplantibacillus, Lentilactobacillus, and Lacticaseibacillus growth, but the microbial species responsible for fermentation differed among the treatments. High species diversity and various Gram-negative bacteria, such as Flavitalea sp., Pantoea agglomerans, Acinetobacter pittii, Turicibacter sanguinis, and Ralstonia pickettii, were found in the uninoculated LAB treatments. A beneficial bacterium, Lactobacillus johnsonii, was discovered for the first time in whole-plant paper mulberry silage. LAB inoculation simplifies the microbial community structure, and beneficial Lactobacillus as a key species aggregates in the inoculated treatment group. However, L. rhamnosus inoculation alone may have limited bacteriostatic activity against in whole-plant paper mulberry silage. Compared with silage lacking corn flour, amino sugar and nucleotide sugar metabolism, galactose metabolism, the phosphotransferase system and the pentose phosphate pathway metabolic activity were increased in corn flour-containing silage. Whole-plant paper mulberry can be used as a high-quality silage to provide high-quality feed resources for sustainable ruminant livestock production. Moreover, additive use is necessary for preparing paper mulberry silage.

Building polygons plays an important role in urban management. Although leveraging deep learning techniques for building polygon extraction offers advantages, the models heavily rely on a large number of training samples to achieve good generalization performance. In scenarios with small training samples, the models struggle to effectively represent diverse building structures and handle the complexity introduced by the background. A common approach to enhance feature representation is fine-tuning a pre-trained model on a large dataset specific to the task. However, the fine-tuning process tends to overfit the model to the task area samples, leading to the loss of generalization knowledge from the large dataset. To address this challenge and enable the model to inherit the generalization knowledge from the large dataset while learning the characteristics of the task area samples, this paper proposes a knowledge distillation-based framework called Building Polygon Distillation Network (BPDNet). The teacher network of BPDNet is trained on a large building polygon dataset containing diverse building samples. The student network was trained on a small number of available samples from the target area to learn the characteristics of the task area samples. The teacher network provides guidance during the training of the student network, enabling it to learn under the supervision of generalization knowledge. Moreover, to improve the extraction of buildings against the backdrop of a complex urban context, characterized by fuzziness, irregularity, and connectivity issues, BPDNet employs the Dice Loss, which focuses attention on building boundaries. The experimental results demonstrated that BPDNet effectively addresses the problem of limited generalization by integrating the generalization knowledge from the large dataset with the characteristics of the task area samples. It accurately identifies building polygons with diverse structures and alleviates boundary fuzziness and connectivity issues.

Early detection of pathogen cross-transmission events and environmental reservoirs is needed to control derived nosocomial outbreaks. Whole-genome sequencing (WGS) is considered the gold standard for outbreak confirmation, but, in most cases, it is time-consuming and has elevated costs. Consequently, the timely incorporation of WGS results to conventional epidemiology (CE) investigations for rapid outbreak detection is scarce. Fourier transform infrared spectroscopy (FTIR) is a rapid technique that establishes similarity among bacteria based on the comparison of infrared light absorption patterns of bacterial polysaccharides and has been used as a typing tool in recent studies. The aim of the present study was to evaluate the performance of the FTIR as a first-line typing tool for the identification of extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-Kp) outbreaks in the hospital setting in comparison with CE investigations using WGS as the gold standard method. Sixty-three isolates of ESBL-Kp collected from 2018 to 2021 and classified according to CE were typed by both FTIR and WGS. Concordance was measured using the Adjusted Rand index (AR) and the Adjusted Wallace coefficient (AW) for both CE and FTIR clustering considering WGS as the reference method. Both AR and AW were significantly higher for FTIR clustering than CE clustering (0.475 vs. 0.134, p = 0.01, and 0.521 vs. 0.134, p = 0.009, respectively). Accordingly, FTIR inferred more true clustering relationships than CE (38/42 vs. 24/42, p = 0.001). However, a similar proportion of genomic singletons was detected by both FTIR and CE (13/21 vs. 12/21, p = 1). This study demonstrates the utility of the FTIR method as a quick, low-cost, first-line tool for the detection of ESBL-Kp outbreaks, while WGS analyses are being performed for outbreak confirmation and isolate characterization. Thus, clinical microbiology laboratories would benefit from integrating the FTIR method into CE investigations for infection control measures in the hospital setting.

ObjectivesTo assess the potential of a radiomics approach of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) in the diagnosis of cardiac amyloidosis (CA).Materials and MethodsThis retrospective study included 200 patients with biopsy-proven light-chain (AL) amyloidosis. CA was diagnosed on the basis of systemic amyloidosis confirmed with evidence of cardiac involvement by imaging and clinical biomarkers. A total of 139 patients [54 ± 8 years, 75 (54%) men] in our institution were divided into training cohort [n = 97, mean age of 53 ± 8 years, 54 (56%) men] and internal validation cohort [n = 42, mean age: 56 ± 8 years, 21 (50%) men] with a ratio of 7:3, while 61 patients [mean age: 60 ± 9 years, 42 (69%) men] from the other two institutions were enrolled for external validation. Radiomics features were extracted from global (all short-axis images from base-to-apex) left ventricular (LV) myocardium and three different segments (basal, midventricular, and apex) on short-axis LGE images using the phase-sensitive reconstruction (PSIR) sequence. The Boruta algorithm was used to select the radiomics features. This model was built using the XGBoost algorithm. The two readers performed qualitative and semiquantitative assessment of the LGE images based on the visual LGE patterns, while the quantitative assessment was measured using a dedicated semi-automatic CMR software. The diagnostic performance of the radiomics and other qualitative and quantitative parameters were compared by a receiver operating characteristic (ROC) curve analysis. A correlation between radiomics and the degree of myocardial involvement by amyloidosis was tested.ResultsA total of 1,906 radiomics features were extracted for each LV section. No statistical significance was indicated between any two slices for diagnosing CA, and the highest area under the curve (AUC) was found in basal section {0.92 [95% confidence interval (CI), 0.86–0.97] in the LGE images in the training set, 0.89 (95% CI, 0.79–1.00) in the internal validation set, and 0.92 (95% CI, 0.85–0.99) in the external validation set}, which was superior to the visual assessment and quantitative LGE parameters. Moderate correlations between global or basal radiomics scores (Rad-scores) and Mayo stage in all patients were reported (Spearman’s Rho = 0.61, 0.62; all p < 0.01).ConclusionA radiomics analysis of the LGE images provides incremental information compared with the visual assessment and quantitative parameters on CMR to diagnose CA. Radiomics was moderately correlated with the severity of CA. Further studies are needed to assess the prognostic significance of radiomics in patients with CA.

IntroductionThe perspectives of healthcare professionals (HCPs) are pivotal to co-development of self-management strategies for patients with diabetes. However, literature has been largely limited to perspectives of patients within the context of a Western healthcare setting. This study aims to explore factors influencing diabetes self-management in adult patients with diabetes from the perspectives of HCPs and their views of the value of mHealth application for diabetes self-management.Materials and MethodsWe conducted focus group discussions (FGD) with purposively selected HCPs in Singapore. All FGDs were audio-recorded and transcribed verbatim. Thematic analysis was conducted using NVivo 12.ResultsA total of 56 HCPs participated in the study. Barriers to self-management included limited patient commitment to lifestyle changes, suboptimal adherence to medication and treatment, patient resistance to insulin initiation and insufficient rapport between patients and HCPs. Patients’ perceived susceptibility to complications, social support from family and community, multidisciplinary team care and patient’s understanding of the benefits of self-care were viewed as facilitating self-management. HCPs saw mHealth apps as a vital opportunity to engage patients in the self-management of conditions and empower them to foster behavior changes. Yet, there were concerns regarding patient’s limited digital literacy, lack of integration into routine electronic system and reluctance.DiscussionWe identified a set of factors influencing self-management in adult patients with diabetes and useful app features that can empower patients to manage their conditions. Findings will inform the development of a mHealth application, and its features designed to improve self-care.

This study aimed to explore the changes in the microbial community on the silage material surface and during the ensiling process of whole-plant maize in different regions. Whole-plant maize silages were sampled in Ziyun, Guanling, and Weinning counties within warm and humid climate areas in southern China. Silages were sampled at 0, 2, 5, 10, 20, and 45 days during ensiling. The nutritional components, fermentation properties, and microbiomes were examined to evaluate the influence of sampling area and fermentation time on the quality of silage. The results showed that the pH values of all silages significantly decreased (

Plant phyllosphere bacteria are vital for plant health and productivity and are affected by both abiotic and biotic factors. In this study, we surveyed the structure of the phyllosphere bacterial community associated with alfalfa. For two varieties of alfalfa, forty-eight samples of phyllosphere communities were collected at two locations over four seasons in 2020. Proteobacteria and actinobacteria were associated with the dominating phylum in the bacterial communities of the alfalfa phyllosphere. Sphingomonas was the most abundant genus-level bacteria, followed by Methylobacterium, Burkholderia-Caballeronia-Paraburkholderia, and Pseudomonas. Sampling time had a greater affect than site and variety on alfalfa surface microorganisms. The variation in phyllosphere bacterial community assembly was mostly explained by the season–site interaction (43%), season–variety interaction (35%), and season (28%). Variety, site–variety interaction, and season–site–variety interactions did not have a meaningful effect on phyllosphere bacterial diversity and community structure. The bacterial community in the phyllosphere of alfalfa showed seasonal changes over time. The environmental factors that contributed most to the phyllosphere bacterial community of alfalfa were temperature and sunshine duration, which were significantly positively correlated with most of the dominant bacterial genera in the alfalfa phyllosphere.

Broussonetia papyrifera L. (paper mulberry) is an alternative woody plant, which can used to replace part of the protein feed for ruminants. Ensiling is an effective way to preserve fresh pasture and to solve the problem of stable storage and feed conversion of paper mulberry in the rapid growth period. However, low dry matter (DM), water-soluble carbohydrate, and lactic acid bacteria (LAB) reduce the quality of paper mulberry silage. This study assesses the influence of wilting time (0 h and 3.5 h; lighting: 3.43 × 104 Lux) and three additives (Enterococcus durans, CL; cellulase, CE; and formic acid, FA) on the fermentation quality, aerobic stability, and bacterial community of whole plant B. papyrifera silage. The whole plant B. papyrifera sample was mowed and wilted for 0 h and 3.5 h, and then had CL, CE, or FA added, followed by 60 days of ensiling. The results show all silage samples had high fermentation quality with pH below 4.2, ammonia-nitrogen below 100 g/kg DM, and no detectable butyric acid. The additives protected the DM and the crude protein from protease activity (p < 0.05), and CL was the most effective among them. Furthermore, wilting time influenced the silage’s bacterial communities, but overall, CL treatment had the greatest impact on bacterial communities. Wilting time and formic acid treatment significantly improved aerobic stability (p < 0.05). Enterococcus was positively correlated with lactic acid (LA), while negatively correlated with LA and Weissella (p < 0.001). Enterococcus was identified as the main driver of the whole plant paper mulberry ensiling process in the present study. In conclusion, compared to other additives, LAB is the most effective and economical to improve the fermentation quality and reduce the protein degradation of whole plant paper mulberry silage. Our findings provide a theoretical basis to improve the quality and production of paper mulberry silage.

Our aim was to determine changes in the incidence of CD infection (CDI) following the introduction of a two-step diagnostic algorithm and to analyze CDI cases diagnosed in the study period. We retrospectively studied CDI (January 2009 to July 2018) in adults diagnosed by toxin enzyme immunoassay (EIA) (2009–2012) or toxin-EIA + polymerase chain reaction (PCR) algorithm (2013 onwards). A total of 443 patients with a first episode of CDI were included, 297 (67.1%) toxin-EIA-positive and 146 (32.9%) toxin-EIA-negative/PCR-positive were only identified through the two-step algorithm including the PCR test. The incidence of CDI increased from 0.9 to 4.7/10,000 patient-days (p < 0.01) and 146 (32.9%) toxin-negative CDI were diagnosed. Testing rate increased from 24.4 to 59.5/10,000 patient-days (p < 0.01) and the percentage of positive stools rose from 3.9% to 12.5% (p < 0.01). CD toxin-positive patients had a higher frequency of severe presentation and a lower rate of immunosuppressive drugs and inflammatory bowel disease. Mortality (16.3%) was significantly higher in patients with hematological neoplasm, intensive care unit admission and complicated disease. Recurrences (14.9%) were significantly higher with proton pump inhibitor exposure. The two-step diagnostic algorithm facilitates earlier diagnosis, potentially impacting patient outcomes and nosocomial spread. CD-toxin-positive patients had a more severe clinical presentation, probably due to increased CD bacterial load with higher toxin concentration. This early and easy marker should alert clinicians of potentially more severe outcomes.

Macrolide and fluoroquinolone resistance (MLr/FQr) in Mycoplasma genitalium (MG) infections is concerning worldwide. Current guidelines recommend performing MLr detection in MG-positive cases to adjust antimicrobial therapy. We aimed to evaluate the usefulness of PCR followed by pyrosequencing for MLr detection in comparison with a one-step commercial assay and to assess the prevalence of MLr and FQr in Badalona, Spain. A total of 415 MG-positive samples by Allplex STI-7 (Seegene) were analyzed for MLr detection by pyrosequencing. From those, 179 samples were further analyzed for MG and MLr by ResistancePlus® MG kit (SpeeDx) and 100 of them also for fluoroquinolone resistance (FQr) by sequencing the parC gene. Regarding MG detection, Allplex and Resistance Plus® showed an overall agreement of 87%, but this value rose to 95.4% if we compare them for MLr detection. Prevalence of MLr was 23.1% in Badalona, but this rate increased to 73.7% in the HIV-positive patients cohort. FQr detection showed 3% of resistant strains. Pyrosequencing is a convenient and cheap technique for MLr detection, but one-step tools should be considered in high-throughput laboratories. Despite the fact that MLr remained moderate and FQr was low in our study, simultaneous MG and MLr detection would improve patient’s management applying resistance-guided treatment strategies.