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Abstract The inferior vena cava collapsibility index (IVCCI) has been used to predict fluid responsiveness. This study aimed to evaluate the accuracy of the perioperative IVCCI to predict postinduction hypotension (PIH) under general anaesthesia (GA) combined with lumbar plexus sacral plexus block (LSPB) in elderly patients undergoing hip arthroplasty. A total of forty patients aged over 65 years were recruited for this prospective observational study. The diameters of the inferior vena cava (IVC), common iliac vein (CIV) and IVCCI were measured at baseline and 15 min post-LSPB. PIH was defined as a systolic blood pressure less than 90 mmHg or a ≥ 30% drop from baseline; patients were divided into hypotensive and nonhypotensive groups. The primary objective of this study was to evaluate the ability of the IVCCI to predict PIH via receiver operating characteristic (ROC) analysis. The secondary objective was to observe the change in CIV diameter. Eighteen patients (45%) developed PIH during GA. No statistically significant differences in baseline or post-LSPB IVCCI were detected between hypotensive and nonhypotensive patients (p > 0.05), whereas a significant expansion of the CIV (0.83 cm to 1.10 cm) was observed 15 min post-LSPB in all patients (p

Abstract Advances in single-cell transcriptomics provide an unprecedented opportunity to explore complex biological processes. However, computational methods for analyzing single-cell transcriptomics still have room for improvement especially in dimension reduction, cell clustering, and cell–cell communication inference. Herein, we propose a versatile method, named DcjComm, for comprehensive analysis of single-cell transcriptomics. DcjComm detects functional modules to explore expression patterns and performs dimension reduction and clustering to discover cellular identities by the non-negative matrix factorization-based joint learning model. DcjComm then infers cell–cell communication by integrating ligand-receptor pairs, transcription factors, and target genes. DcjComm demonstrates superior performance compared to state-of-the-art methods.

Abstract The inference of cell–cell communication (CCC) is crucial for a better understanding of complex cellular dynamics and regulatory mechanisms in biological systems. However, accurately inferring spatial CCCs at single-cell resolution remains a significant challenge. To address this issue, we present a versatile method, called DeepTalk, to infer spatial CCC at single-cell resolution by integrating single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data. DeepTalk utilizes graph attention network (GAT) to integrate scRNA-seq and ST data, which enables accurate cell-type identification for single-cell ST data and deconvolution for spot-based ST data. Then, DeepTalk can capture the connections among cells at multiple levels using subgraph-based GAT, and further achieve spatially resolved CCC inference at single-cell resolution. DeepTalk achieves excellent performance in discovering meaningful spatial CCCs on multiple cross-platform datasets, which demonstrates its superior ability to dissect cellular behavior within intricate biological processes.

Bacillus thuringiensis crystal (Cry) proteins have been expressed in commercial transgenic crops for nearly 30 years, providing safe and effective control of insect pests and significantly reducing the application of hazardous chemical pesticides. B. thuringiensis crystal proteins have also been shown to target parasitic nematodes, including plant parasitic nematodes. Recently, transgenic soybean crops expressing Cry14Ab have been shown to provide control against the soybean cyst nematode Heterodera glycines, marking the first time a crystal protein is being commercialized in transgenic crops for control of a nematode pest. However, apart from H. glycines and the free-living nematode, Caenorhabditis elegans, the breadth of nematode activity of Cry14Ab, e.g., against gastrointestinal parasitic nematodes (GINs), has not been reported. Here we study the efficacy of Cry14Ab against a wide range of gastrointestinal nematode parasites (GINs) in vitro and in vivo. We find that Cry14Ab is effective in vitro against the barber's pole worm Haemonchus contortus larvae, small strongyles cyathostomin larvae, the hookworm Ancylostoma ceylanicum adults, the roundworm Ascaris suum L4 larvae, and the whipworm Trichuris muris adults. In rodents infected with GIN parasites, Cry14Ab is effective as an in vivo anthelmintic against the hookworms A. ceylanicum and N. americanus, against the mouse parasite Heligmosomoides polygyrus bakeri, and against the roundworm A. suum. Cry14Ab also variably reduces the reproduction of the whipworm T. muris in vivo. Using optimized profile Markov Models, we looked for other putative anthelmintic Cry proteins and, within this list, identified a Bt crystal protein, GenBank accession no. MF893203, that we produced and demonstrated intoxicated GINs. This protein, with 90% amino acid identity to Cry14Ab, is active against C. elegans, A. ceylanicum adults, and A. suum L4 larvae in vitro. MF893203 was given the official designation of Cry14Ac. Cry14Ac is also an effective in vivo anthelmintic against A. ceylanicum hookworms in hamsters and intestinal A. suum in mice. Taken together, our results demonstrate that Cry14Ab and Cry14Ac have wide therapeutic utility against GINs.

Abstract SMYD3 (SET and MYND domain‐containing 3) is a histone lysine methyltransferase highly expressed in different types of cancer(s) and is a promising epigenetic target for developing novel antitumor therapeutics. No selective inhibitors for this protein have been developed for cancer treatment. Therefore, the current study describes developing and characterizing a novel small molecule ZYZ384 screened and synthesized based on SMYD3 structure. Virtual screening was initially used to identify a lead compound and followed up by modification to get the novel molecules. Several technologies were used to facilitate compound screening about these novel molecules' binding affinities and inhibition activities with SMYD3 protein; the antitumor activity has been assessed in vitro using various cancer cell lines. In addition, a tumor‐bearing nude mice model was established, and the activity of the selected molecule was determined in vivo. Both RNA‐seq and chip‐seq were performed to explore the antitumor mechanism. This work identified a novel small molecule ZYZ384 targeting SMYD3 with antitumor activity and impaired hepatocellular carcinoma tumor growth by reducing H3K4 trimethylation of the Rac1 promoter triggering the tumor cell cycle arrest through the AKT pathway.

Abstract Background Neuronal guanine nucleotide exchange factor (NGEF) plays a key role in several cancers; however, its role in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to evaluate the efficacy of NGEF as a prognostic biomarker and potential therapeutic target for LUAD. Methods NGEF expression data for multiple cancers and LUAD were downloaded from multiple databases. The high- and low-NGEF expression groups were constructed based on median NGEF expression in LUAD samples, and then performed Kaplan–Meier survival analysis. Differentially expressed genes (DEGs) from the two NGEF expression groups were screened and applied to construct a protein-protein interaction network. The primary pathways were obtained using gene set enrichment analysis. The associations between NGEF expression and clinical characteristics, immune infiltration, immune checkpoint inhibitors (ICIs), sensitivity to chemotherapy, and tumor mutation burden (TMB) were investigated using R. Levels of NGEF expression in the lung tissue was validated using single-cell RNA sequencing, quantitative polymerase chain reaction (qPCR), immunohistochemical staining, and western blot analysis. Results The expression of NGEF mRNA was upregulated in multiple cancers. mRNA and protein expression levels of NGEF were higher in patients with LUAD than in controls, as validated using qPCR and western blot. High NGEF expression was an independent prognostic factor for LUAD and was associated with advanced tumor stage, large tumor size, more lymph node metastasis, and worse overall survival (OS). A total of 182 overlapping DEGs were screened between The Cancer Genome Atlas and GSE31210, among which the top 20 hub genes were identified. NGEF expression was mainly enriched in the pathways of apoptosis, cell cycle, and DNA replication. Moreover, elevated NGEF expression were associated with a high fraction of activated memory CD4+ T cells and M0 macrophages; elevated expression levels of the ICIs: programmed cell death 1 and programmed cell death 1 ligand 1 expression; higher TMB; and better sensitivity to bortezomib, docetaxel, paclitaxel, and parthenolide, but less sensitivity to axitinib and metformin. Conclusion NGEF expression is upregulated in LUAD and is significantly associated with tumor stages, OS probability, immune infiltration, immunotherapy response, and chemotherapy response. NGEF may be a potential diagnostic and prognostic biomarker and therapeutic target in LUAD.

Abstract In this paper, we consider the existence and uniqueness of solutions for the following nonlinear multi-order fractional differential equation with integral boundary conditions { ( C D 0 + α u ) ( t ) + ∑ i = 1 m λ i ( t ) ( C D 0 + α i u ) ( t ) + ∑ j = 1 n μ j ( t ) ( C D 0 + β j u ) ( t ) + ∑ k = 1 p ξ k ( t ) ( C D 0 + γ k u ) ( t ) + ∑ l = 1 q ω l ( t ) ( C D 0 + δ l u ) ( t ) + σ ( t ) u ( t ) + f ( t , u ( t ) ) = 0 , t ∈ [ 0 , 1 ] , u ″ ( 0 ) = u ‴ ( 0 ) = 0 , u ′ ( 0 ) = η 1 ∫ 0 1 u ( s ) d s , u ( 1 ) = η 2 ∫ 0 1 u ( s ) d s , $$ \textstyle\begin{cases} ({}^{C}D_{0+}^{\alpha}u)(t)+\sum_{i=1}^{m}\lambda _{i}(t)({}^{C}D_{0+}^{\alpha _{i}}u)(t)+ \sum_{j=1}^{n}\mu _{j}(t)({}^{C}D_{0+}^{\beta _{j}}u)(t)\\ \quad{}+\sum_{k=1}^{p}\xi _{k}(t)({}^{C}D_{0+}^{\gamma _{k}}u)(t)+\sum_{l=1}^{q}\omega _{l}(t)({}^{C}D_{0+}^{\delta _{l}}u)(t)\\ \quad{}+\sigma (t)u(t)+f(t,u(t))=0,\quad t\in [0,1],\\ u^{\prime \prime}(0)=u^{\prime \prime \prime}(0)=0,\qquad u^{\prime}(0)=\eta _{1}\int _{0}^{1}u(s)\,ds,\qquad u(1)=\eta _{2}\int _{0}^{1}u(s)\,ds, \end{cases} $$ where 0 < δ 1 < δ 2 < ⋯ < δ q < 1 < γ 1 < γ 2 < ⋯ < γ p < 2 < β 1 < β 2 < ⋯ < β n < 3 < α 1 < α 2 < ⋯ < α m < α < 4 $0

In this paper, we consider the H-Toeplitz and Toeplitz operators acting on the Bergman space. First, we describe the characterizations of commutativity of two H-Toeplitz operators with certain harmonic symbols. For the general case, it seems very hard. As an extension to the study of Toeplitz operators on the Bergman space, we present the necessary and sufficient conditions of the commutativity of the H-Toeplitz operator and the Toeplitz operator with non-harmonic symbols.

ABSTRACTThe coronavirus disease 2019 (COVID-19) pandemic has generated significant economic loss and an unprecedented challenge to people’s livelihoods. Using household data collected in November 2020, this study shows that the COVID-19 outbreak has significantly affected consumers’ perceptions and consumption of genetically modified (GM) food in China. Their perceptions and purchase intentions have turned more negative, and their actual purchase of GM food has decreased after the COVID-19 outbreak. The study’s results also indicate that consumers with more knowledge of genetic modification technology are less likely to change their perceptions of GM food.

Ecosystem services (ESs) research is crucial for comprehending the intricate interplay between humans activities and the environment, particularly in ecologically sensitive regions like Central Asia, which straddles the transition from semi-arid to arid climates. Despite the ecological significance of these arid regions, research on ESs remains limited. In this study, we applied the InVEST model to analyze the spatial characteristics of multiple ESs, including water yield (WY), soil retention (SR), carbon storage (CS), and habitat quality (HQ), in Central Asia. Our findings unveil significant zonal disparities in the distribution of ESs and trade-offs across the region. WY, SR and WY-SR display distinct vertical zonation patterns, while CS and HQ exhibit both latitudinal and vertical zonation patterns. Trade-offs, with the exception of WY-SR, mostly exhibit a striped distribution pattern. Additionally, based on the GeoDetector approach, we identified key influencing factors, encompassing land use type, precipitation, evapotranspiration, temperature, vegetation coverage, soil depth, and soil organic matter. Notably, we discovered that the relationship between these factors and ESs, as well as trade-offs, is non-linear, with certain factors exhibiting optimal thresholds for maintaining either high or low levels of ESs and trade-offs.This study advances our understanding of ESs in the arid regions of Central Asia, offering valuable insights for regional ecosystem management and coordinated development. By shedding light on the non-linear dynamics of ESs and their response to influencing factors, it underscores the importance of further research to support sustainable development efforts in these regions. Future research can build upon these findings to develop policies and interventions that harness ESs for the benefit of the environment and local communities.

Objective: Dual task (DT) is a commonly used paradigm indicative of executive functions. Brain activities during DT walking is usually measured by portable functional near infrared spectroscopy (fNIRS). Previous studies focused on cortical activation in prefrontal cortex and overlooked other brain regions such as sensorimotor cortices. This study is aimed at investigating the modulations of cortical activation and brain network efficiency in multiple brain regions from single to dual tasks with different complexities and their relationships with DT performance. Methods: Forty-two healthy adults [12 males; mean age: 27.7 (SD=6.5) years] participated in this study. Participants performed behavioral tasks with portable fNIRS simultaneous recording. There were three parts of behavioral tasks: cognitive tasks while standing (serial subtraction of 3′s and 7′s), walking alone and DT (walk while subtraction, including serial subtraction of 3′s and 7′s). Cognitive cost, walking cost and cost sum (i.e., sum of cognitive and walking costs) were calculated for DT. Cortical activation, local and global network efficiency were calculated for each task. Results: The cognitive cost was greater and the walking cost was less during DT with subtraction 3′s compared with 7′s (P’s = 0.032 and 0.019, respectively). Cortical activation and network efficiency were differentially modulated among single and dual tasks (P's < 0.05). Prefrontal activation during DT was positively correlated with DT costs, while network efficiency was negatively correlated with DT costs (P's < 0.05). Conclusions: Our results revealed prefrontal over-activation and reduced network efficiency in individuals with poor DT performance. Our findings suggest that reduced network efficiency could be a possible mechanism contributing to poor DT performance, which is accompanied by compensatory prefrontal over-activation.

BackgroundAlthough numerous studies have used Chinese samples to examine the consequences of parental phubbing, these studies focused on children’s mental health and peer interaction. No research to date has directly explored the association between parental phubbing and child–parent interaction. Since parental phubbing is a way how parents interact with their children (parent–child), it might be associated with the way how children interact with their parents (child–parent), such as filial piety behavior, which prescribes how children behave toward their parents and remains one of the goals of parents in educating their children in modern Chinese society. Based on social exchange theory and social gender theory, this study investigated the impact of parental phubbing on filial piety behavior and tested its mediation of perceived parental rejection, its moderation of gender among children and adolescents.MethodsThis study was conducted using a questionnaire method. A total of 753 students from Grade 4 to 9 (Mage = 12.28 years, SD = 1.81 years) was surveyed using the Parental Phubbing Scale, Perceived Parental Rejection Questionnaire, and the revised Dual Filial Piety Scale.ResultsFirst, parental phubbing was negatively correlated with reciprocal filial piety (RFP) behavior, but not correlated with authoritarian filial piety (AFP) behavior. Second, perceived parental rejection played a mediating role between parental phubbing and RFP behavior. Third, this direct effect was moderated by gender, in that it was stronger for boys than for girls.ConclusionThese findings suggest that there are intergenerational costs of phubbing, such as reducing children and adolescents’ RFP behavior. The present study is the first to combine parent–child interaction in the digital media era (parental phubbing) with traditional Chinese child–parent interaction (RFP behavior), which expands the research topic on the influence of parental phubbing on children and adolescents’ psychological development.

Background: Continuous theta burst stimulation and intermittent theta burst stimulation are clinically popular models of repetitive transcranial magnetic stimulation. However, they are limited by high variability between individuals in cortical excitability changes following stimulation. Although electroencephalography oscillations have been reported to modulate the cortical response to transcranial magnetic stimulation, their association remains unclear. This study aims to explore whether machine learning models based on EEG oscillation features can predict the cortical response to transcranial magnetic stimulation. Method: Twenty-three young, healthy adults attended two randomly assigned sessions for continuous and intermittent theta burst stimulation. In each session, ten minutes of resting-state electroencephalography were recorded before delivering brain stimulation. Participants were classified as responders or non-responders based on changes in resting motor thresholds. Support vector machines and multi-layer perceptrons were used to establish predictive models of individual responses to transcranial magnetic stimulation. Result: Among the evaluated algorithms, support vector machines achieved the best performance in discriminating responders from non-responders for intermittent theta burst stimulation (accuracy: 91.30%) and continuous theta burst stimulation (accuracy: 95.66%). The global clustering coefficient and global characteristic path length in the beta band had the greatest impact on model output. Conclusion: These findings suggest that EEG features can serve as markers of cortical response to transcranial magnetic stimulation. They offer insights into the association between neural oscillations and variability in individuals' responses to transcranial magnetic stimulation, aiding in the optimization of individualized protocols.

Shale gas is an important alternative natural gas source that can meet China's growing energy demand. However, methane emissions during shale gas production could largely determine whether it could be considered as a bridging clean energy source. In this study, we performed methane emission measurements using three methods (on-site optical gas imaging, on-site methane patrolling, and downwind measurement) at shale gas production sites in Sichuan province, China, covering 18 well sites with 81 wells. The results showed that flowback water tanks were the major methane sources, with valves, separators, chemical injection pumps, and pneumatic controllers as other sources. The methane concentrations inside the 18 sites ranged from 1.42 to 459 μmol mol−1, with over 59% of the sites having the highest concentration less than 50 μmol mol−1. The optical gas imaging method, with its low detection limit over 5000 μmol mol−1, could not capture the emission effectively. The three successful downwind measurements resulted in site level emission rates between 0.02 and 0.17 kg h−1. When divided by the number of wells at each site, the emission intensity was 4%–28% of the wellhead emission factor for natural gas production in China. More measurements are required to better quantify methane emissions from shale gas sites in China. For sites in mountainous regions or long-term low-wind regions, detection methods other than downwind measurements should be suitable for quantifying site-level emissions.

In this paper, we characterize when the product of two H-Toeplitz operators to be another H-Toeplitz with one general and another quasihomogeneous symbols. Also, we describe the product of H-Toeplitz operator and Toeplitz operator to be another H-Toeplitz with certain harmonic symbols.

Abstract Ventriculoperitoneal shunt (VPS) placement is the standard procedure in the management of hydrocephalus. The introduction of laparoscopy allows better visualization during the operation and a more reliable placement of the peritoneal terminal of the catheter, which significantly decreases postoperative obstruction and malposition rates. However, the fixation methods of the peritoneal terminal of the catheter have not been previously discussed. The indications, techniques, and complications were compared between conventional VPS and laparoscopy-guided VPS. Furthermore, same analyses were performed within the laparoscopy-guided VPS group subdivided by three different techniques of the fixation of the peritoneal terminal of catheter, including suture and ligature, titanium clip fixation, and subcutaneous fixation. A total of 137 patients with hydrocephalus who received VPS treatment was retrospectively studied, 85 of which were laparoscopy-guided, and 52 were not. The distal ends of the catheters were all placed in the suprahepatic space. At least one year (mean 28.6 months) follow-up was given postoperatively. The average duration of the whole operation was 45 min for suture and ligature, 40 min for titanium clip fixation, and 30 min for the subcutaneous fixation, respectively. Six patients (4.4%) had obstructive of the ventricular catheter in total. The success rates for the laparoscopy-assisted VPS procedure and the conventional VPS procedure were 87.1% (74/85) and 80.8% (42/52), respectively. Within subgroups of the laparoscopy-assisted VPS divided by fixation methods, the procedures were successful in 85.2% (23/27) of suture and ligation, 82.1% (23/28) of titanium clip fixation, and 93.3% (28/30) of subcutaneous fixation, respectively. Two patients had dislocated shunt tube in peritoneal end in laparoscopy group, all in the titanium clip fixation subgroups. The laparoscopy-assisted VPS insertion is an ideal shunt method for its effectiveness and lesser complication rate after operation. The subcutaneous fixation method of the peritoneal terminal of catheter might be the optimal fixation technique.

Abstract Background Precise occlusal design of implant-supported fixed prostheses is difficult to achieve by the conventional wax-up method, often requiring chairside adjustments. The computer-aided design (CAD) method is promising. This study aims to compare the occlusal contacts and clearance of posterior implant-supported single crowns designed by the CAD and conventional methods. Methods Sample size calculation indicated fourteen samples per group. Two sets of type-IV plaster casts with a single implant analog inserted in the posterior teeth region were mounted as master casts in a mechanical articulator in maximal intercuspal position (MIP). Seven working cast sets were obtained from each master cast by a closed tray technique, and mounted in MIP. Two implant-supported single crowns were designed with an occlusal clearance to achieve light occlusal contact in each working cast set by CAD and conventional method, separately. For the CAD group, the crown was designed in digital models obtained by scanning the working casts. For the conventional group, wax-up of the crown was prepared on the working casts and scanned to generate a STL file. In the working and master casts, mean and minimum occlusal clearances in the designed occlusal contact area of the both finished prostheses were calculated using the occlusal clearance (OC) and occlusal record (OR) method. The prostheses’ occlusion was evaluated in master casts. Results For the evaluation in the working casts, both design methods had similar mean occlusal clearances by the OC method (195.4 ± 43.8 vs. 179.8 ± 41.8 μm; P = 0.300), while CAD group resulted in a significantly larger minimum occlusal clearance in the designed occlusal contact area (139.5 ± 52.3 vs. 99.8 ± 43.8 μm; P = 0.043). Both design methods had similar mean and minimum occlusal clearances by the OR method (P > 0.05). For the evaluation in the master casts, both design techniques had similar mean and minimum occlusal clearances, number and distribution of occlusal contacts, and lateral interference ratios (P > 0.05). Conclusion Occlusal contact and clearance of posterior implant-supported single crowns designed by the CAD method can be at least as good as those designed by the conventional wax-up method.

Labyrinthine acoustic metamaterials are good choices for realizing sound insulation, acoustic stealth, and acoustic lenses by virtue of their stable performance and rich modes. We design a labyrinthine acoustic metamaterial with eight resonance units by utilizing triangular self-similarity. First, with the help of eigenstate analysis, it is demonstrated that it has monopolar resonance and multipolar resonance modes. Then, the physical mechanisms that generate transmission valleys and acoustic isolation peaks are analyzed by applying the equivalent medium theory and the vibrational velocity field. Finally, we designed an ultra-sparse distribution (fill rate of 20 %) hypersurface for effective acoustic isolation and noise reduction at 417 Hz (normalized frequency of about λ/12). This study can provide useful assistance in the design of labyrinthine acoustic metamaterials, as well as potential applications in areas where ventilation is required (e.g., acoustic barriers for transportation systems).

BackgroundIt is now understood that APOBEC3 family proteins (A3s) are essential in tumor progression, yet their involvement in tumor immunity and stemness across diverse cancer types remains poorly understood.MethodsIn the present study, comprehensive genome-wide statistical and bioinformatic analyses were conducted to elucidate A3 family expression patterns, establishing clinically relevant correlations with prognosis, the tumor microenvironment(TME), immune infiltration, checkpoint blockade, and stemness across cancers. Different experimental techniques were applied, including RT–qPCR, immunohistochemistry, sphere formation assays, Transwell migration assays, and wound-healing assays, to investigate the impact of A3C on low-grade glioma (LGG) and glioblastoma multiforme (GBM), as well as its function in glioma stem cells(GSCs).ResultsDysregulated expression of A3s was observed in various human cancer tissues. The prognostic value of A3 expression differed across cancer types, with a link to particularly unfavorable outcomes in gliomas. A3s are associated with the the TME and stemness in multiple cancers. Additionally, we developed an independent prognostic model based on A3s expression, which may be an independent prognostic factor for OS in patients with glioma. Subsequent validation underscored a strong association between elevated A3C expression and adverse prognostic outcomes, higher tumor grades, and unfavorable histology in glioma. A potential connection between A3C and glioma progression was established. Notably, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses implicated A3C in immune system-related diseases, with heightened A3C levels contributing to an immunosuppressive tumor microenvironment (TME) in glioma. Furthermore, in vitro experiments substantiated the role of A3C in sustaining and renewing glioma stem cells, as A3C deletion led to diminished proliferation, invasion, and migration of glioma cells.ConclusionThe A3 family exhibits heterogeneous expression across various cancer types, with its expression profile serving as a predictive marker for overall survival in glioma patients. A3C emerges as a regulator of glioma progression, exerting its influence through modulation of the tumor microenvironment and regulation of stemness.

Abstract Rheumatoid arthritis (RA) is an incurable systemic autoimmune disease. Disease progression leads to joint deformity and associated loss of function, which significantly impacts the quality of life for sufferers and adds to losses in the labor force. In the past few decades, RA has attracted increased attention from researchers, the abnormal signaling pathways in RA are a very important research field in the diagnosis and treatment of RA, which provides important evidence for understanding this complex disease and developing novel RA-linked intervention targets. The current review intends to provide a comprehensive overview of RA, including a general introduction to the disease, historical events, epidemiology, risk factors, and pathological process, highlight the primary research progress of the disease and various signaling pathways and molecular mechanisms, including genetic factors, epigenetic factors, summarize the most recent developments in identifying novel signaling pathways in RA and new inhibitors for treating RA. therapeutic interventions including approved drugs, clinical drugs, pre-clinical drugs, and cutting-edge therapeutic technologies. These developments will hopefully drive progress in new strategically targeted therapies and hope to provide novel ideas for RA treatment options in the future.

Abstract Background Medication nonadherence is a significant public health problem as it contributes to poor clinical outcomes and increased healthcare costs. Older patients with multimorbidity and polypharmacy often have low medication adherence. These patients also have a high prevalence of potentially inappropriate medication (PIM) use. Aim To explore risk factors related to medication nonadherence in older patients with multimorbidity and polypharmacy and examine the association between medication nonadherence and PIM use. Method A multicenter cross-sectional study was conducted from May to December 2019 in 16 tertiary hospitals from 12 provinces and cities in China. Data were collected from outpatients 65 years or older with multimorbidity and polypharmacy. The PIMs were evaluated using the 2019 Beers Criteria. Self-reported medication adherence was assessed using the Visual Analog Scale (VAS). Results A total of 773 outpatients were recruited. The prevalence of medication nonadherence was 31.8%. In the univariate analysis, nonadherence was significantly associated with sex, cognitive impairment, stroke, visiting the same physicians, self-administration of medication, the percentage of drug costs ≥ 10% of the medical expenses, and PIMs for the alimentary tract and metabolism. In the multivariate analysis, the results almost paralleled those of the univariate associations. Notably, the use of PIM was significantly associated with medication adherence. Conclusion Several factors that influence medication adherence were identified. Targeted interventions can be implemented to improve medication adherence, such as encouraging self-administering medications and reducing medication expenses.

With increasingly mature global supply chain network with ports as the core, competition among ports has gradually turned to the ability and efficiency of resource integration. However, there is a lack of relevant studies on how to scientifically evaluate the resource integration performance of port enterprises. To comprehensively evaluate the actual effect of port enterprises in process of resource integration, a performance evaluation system of port enterprises resource integration covering 19 secondary indicators from the four dimensions of financial integration, operational efficiency, technological innovation, and realized benefit was built, fuzzy analytic hierarchy process (FAHP) was used to determine weights of various indicators and port enterprises in Zhejiang, Jiangsu, Liaoning, Shandong and Guangdong provinces of China were taken as samples, and fuzzy comprehensive evaluation (FCE) was used to evaluate its resource integration performance. Results show that technological innovation is the primary performance indicator, followed by financial integration indicators, and the impact of realization efficiency and operational efficiency indicators is relatively weak. Resource integration performances of port enterprises in Zhejiang, Jiangsu, Liaoning, Shandong, and Guangdong are generally good. Evaluation results of sample ports reflect the actual integration of ports, and the model can effectively evaluate the performance of port enterprise resource integration. Conclusions obtained from this study provide theoretical support for the scientific performance evaluation of port enterprise resource integration.

H2 is clean energy and an important component of natural gas. Moreover, it plays an irreplaceable role in improving the hydrocarbon generation rate of organic matter and activating ancient source rocks to generate hydrocarbon in Fischer-Tropsch (FT) synthesis and catalytic hydrogenation. Compared with hydrocarbon reservoir system, a complete hydrogen (H2) accumulation system consists of H2 source，reservoirs and seal. In nature, the four main sources of H2 are hydrolysis, organic matter degradation, the decomposition of substances such as methane and ammonia, and deep mantle degassing. Because the complex tectonic activities, the H2 produced in a geological environment is generally a mixture of various sources. Compared with the genetic mechanisms of H2, the migration and preservation of H2, especially the H2 trapping, are rarely studied. A necessary condition for large-scale H2 accumulation is that the speed of H2 charge is much faster than diffusion loss. Dense cap rock and continuous H2 supply are favorable for H2 accumulation. Moreover, H2O in the cap rock pores may provide favorable conditions for short-term H2 accumulation.

Abstract Background Increasing rates of childhood obesity worldwide are a serious threat to the health of school-aged children. Unhealthy behavioral habits are modifiable factors in the control of childhood obesity, and personal and family factors are key influencing factors of behavioral habits in school-aged children. This study assessed the relationship between overweight/obesity, energy balance-related behaviors (EBRB), and their influencing factors in school-aged children. Methods This cross-sectional survey included 4412 primary school-aged (10–12 years) students who underwent body tests and were selected through stratified sampling in the Northeast, North, Northwest, and Southwest regions of China from March to July 2021. Independent sample t test was used to compare differences between behaviors and influencing factors of energy balance among overweight/obesity and normal weight students. Logistic regression analysis was used to assess the influence of EBRB on body shape. Multiple linear regression was used to assess the influence of personal and family factors on EBRB effects. Results Compared with normal-weight students, number of breakfasts consumed per week by overweight/obese students was significantly lower (p

Metamaterials with low-frequency band gap have always been the focus of research. For this reason, many researchers have proposed many structural design schemes. In this paper, an innovative star-shaped hybrid metamaterial structure is proposed. Based on Bloch's theorem and finite element method, a dynamic model of the proposed structure is established, the band gap characteristics of the proposed structure are analyzed, and the generation mechanism of band gap is discussed with the mode shape of specific frequency. Then, the propagation characteristics of elastic wave in the proposed structure are analyzed by using the dispersion surface and group velocity images, and the attenuation region of vibration transmission in the finite periodic structure is consistent with the frequency range of band gap. Finally, the relationship between band gap and structure parameters is explored. The results show that the proposed structure has good band gap characteristics in the frequency range of 1000 Hz, the lowest frequency of band gap reaches 60.207 Hz, and the total band gap width accounts for 54.463%. This research opens up an ideological route for the design of low frequency metamaterial structures.

Abstract Background Cleft lip repair surgery always results in visible scarring. It has been proved that scar formation can be reduced by inhibiting the p38 mitogen-activated protein kinases (p38MAPKs) signaling pathway. However, the interaction between p38MAPK and Smads in scar formation is still controversial. Methods This study was designed to investigate whether inhibition of p38MAPK reduces postoperative scar formation of cleft lips on rabbits via the Smads signaling pathway. Scar models in rabbits after cleft lip surgery were created and their fibroblasts were extracted. Then the expression of p38MAPK was disturbed by adenovirus in vitro and Vivo. The scar thickness was measured and scar tissues were excised for Sirius red staining and immunohistochemistry to detect the expression of type I collagen (col I), type III collagen (col III), and α-smooth muscle actin (α-SMA). The underlying mechanisms of p38MAPK knockdown on the extracellular matrix and Smad signaling pathway were invested in vitro using the EdU assay, Western blot, RT PCR, and immunofluorescence. Results p38MAPK knockdown suppresses the expression of p-smad3 and p-smad2 in fibroblasts, modulating the expression of its target genes, such as α-SMA, col I, and col III. When Ad-P38MAPK-1 was injected into lip scar, it reduced the expression of scar-related genes and scar thickness when compared to the negative control groups. Conclusions In rabbits, inhibiting p38MAPK expression prevents scar proliferation through inhibiting the Smad signaling pathway after cleft lip surgery.

BackgroundSiglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods.MethodsThe bioinformatics approach was used to examine Siglec15 mRNA expression in gliomas based on TCGA, CGGA, and GEO datasets. Then, the predictive value of Siglec15 expression on progression-free survival time (PFST) and overall survival time (OST) in glioma patients was comprehensively described.The TCGA database was screened for differentially expressed genes (DEGs) between the high and low Siglec15 expression groups, and enrichment analysis of the DEGs was performed. The Siglec15 protein expression and its prognostic impact in 92 glioma samples were explored using immunohistochemistry Next, the relationships between Siglec15 expression and infiltrating immune cells, immune regulators and multiple immune checkpoints were analysed.ResultsBioinformatics analyses showed that high Siglec15 levels predicted poor clinical prognosis and adverse recurrence time in glioma patients. In the immunohistochemical study serving as a validation set, Siglec15 protein overexpression was found in 33.3% (10/30) of WHO grade II, 56% (14/25) of WHO grade III, and 70.3% (26/37) of WHO grade IV gliomas respectively. Siglec15 protein overexpression was also found to be an independent prognostic indicator detrimental to the PFST and OST of glioma patients. Enrichment analysis showed that the DEGs were mainly involved in pathways associated with immune function, including leukocyte transendothelial migration, focal adhesion, ECM receptor interaction, and T-cell receptor signaling pathways. In addition, high Siglec15 expression was related to M2 tumor-associated macrophages (TAMs), N2 tumor-infiltrating neutrophils, suppressive tumor immune microenvironment, and multiple immune checkpoint molecules. Immunofluorescence analysis confirmed the colocalization of Siglec15 and CD163 on TAMs.ConclusionSiglec15 overexpression is common in gliomas and predicts an adverse recurrence time and overall survival time. Siglec15 is a potential target for immunotherapy and a potential TAMs regulator that is involved in the suppressed immunomicroenvironment in gliomas.

Background: Previous evidence on the association of red blood cell distribution width (RDW) with bortezomib-induced peripheral neuropathy (BIPN) is limited. As a result, in this single-center retrospective cohort analysis, the link between RDW and BIPN was investigated. Methods: This study4 comprised 376 patients with primary multiple myeloma (MM) who attended the Department of Haematology at Guizhou Provincial People's Hospital between 2013 and 2021. RDW and the occurrence of BIPN were the exposure and outcome variables, respectively. Demographic characteristics, pharmacological agents, co-morbidities, and MM-related indicators were all included as covariates. To investigate the relationship between RDW and BIPN, binary logistic regression and two-piecewise linear regression were utilized. Results: The relationship between RDW and BIPN was found to be non-linear. RDW was not significantly associated with the risk of BIPN (odds ratio (OR): 0.99; 95% confidence interval (CI): 0.95 to 1.02; p-value: 0.4810) to the left of the inflection point (RDW = 72.3); to the right of the inflection point, each 1 ft increase in RDW was associated with an 7% increase in the risk of BIPN (OR: 1.07; 95% CI: 1.01 to 1.15; p-value: 0.046). Conclusion: The relationship between RDW and the risk of BIPN demonstrated a threshold effect, with RDW exceeding 72.3 fl, indicating a relatively significant risk of BIPN.

To achieve multi-frequency vibration suppression and wave propagation modulation, eight branching ligament structures for wind models are proposed. Using lattice theory, dynamical model and finite element release method, the structures are verified to have multi-frequency bandgaps. By attaching a solid disc at the center of the model, the bandgap coverage of the structure is improved and the bandgap frequency is reduced. The modal analysis shows that the vibration of branch ligaments and border ligaments has a suppression effect on elastic waves. The phase constant surface, phase velocity and wave propagation direction plots at specific frequencies are calculated to verify the directional and regional nature of wave propagation. And the good correspondence of group velocity and wave propagation finite element simulation results at specific frequencies. Finally, the calculated bandgap frequency range is compared with the vibration transfer function, and the two agree well. And the stress cloud diagram also shows that the optimized structure has an excellent vibration suppression capability. The innovatively designed structure has the combined advantages of light weight, ease of fabrication, wide frequency and low frequency vibration control, while the integrated in-plane wave analysis provides the theoretical basis for structural optimization.

Background: Recent evidence has emerged regarding the modification of the relationship between the enhancer RNA (eRNA) colorectal neoplasia differentially expressed (CRNDE) and the prognosis of patients with cancer. Nevertheless, the role of CRNDE in pan-cancer and tumour immune microenvironment (TIME) remains largely unexplored. Methods: Multiple bioinformatic methods were employed to unravel the role of elncRNA CRNDE in a wide range of cancers from the perspective of the expression patterns, prognosis, tumour immunity, and the association between CRNDE and its target gene IRX5 based on the public database. A nomogram was created by integrating independent factors. Gene set enrichment analysis (GSEA) was used to determine the potential signalling pathway mechanisms. Molecular biology experiments including RT-qPCR, MTT, Transwell, and wound-healing analyses were performed to evaluate the proliferation, migration, and invasion of glioma cells. Finally, RT-qPCR and immunohistochemistry were performed to analyse the expression and function of CRNDE in gliomas of different grades. Nissl staining was used to evaluate the potential effects of CRNDE knockdown in glioblastoma tissues. Results: CRNDE was dysregulated and associated with clinical features in 15 of the 33 cancer types. The survival analysis showed that high CRNDE expression might lead to a worsened prognosis among the six cancer types. CRNDE might be involved in immune regulation in multiple cancer types. CRNDE correlated with multiple tumours and immune-related pathways. Additionally, CRNDE knockdown inhibited glioma cell proliferation, migration, and invasion. Nissl staining confirmed that CRNDE siRNA notably decreased tumour growth. A stronger correlation between immune cells and CRNDE/IRX5 in lower-grade glioma than in glioblastoma multiforme tissues, and an association with IRX5 and immune checkpoint gene NRP1 were observed. Conclusions: An Enhancer RNA CRNDE may serve as a biomarker for cancer immunologic infiltration and poor prognosis, providing a new approach for cancer treatment.

ObjectiveThe ability of motor-inhibitory control is critical in daily life. The physiological mechanisms underlying motor inhibitory control deficits remain to be elucidated. Beta band oscillations have been suggested to be related to motor performance, but whether they relate to motor-inhibitory control remains unclear. This study is aimed at systematically investigating the relationship between beta band oscillations and motor-inhibitory control to determine whether beta band oscillations were related to the ability of motor-inhibitory control.MethodsWe studied 30 healthy young adults (age: 21.6 ± 1.5 years). Stop-signal reaction time (SSRT) was derived from stop signal task, indicating the ability of motor-inhibitory control. Resting-state electroencephalography (EEG) was recorded for 12 min. Beta band power and functional connectivity (including global efficiency) were calculated. Correlations between beta band oscillations and SSRT were performed.ResultsBeta band EEG power in left and right motor cortex (MC), right somatosensory cortex (SC), and right inferior frontal cortex (IFC) was positively correlated with SSRT (P’s = 0.031, 0.021, 0.045, and 0.015, respectively). Beta band coherence between bilateral MC, SC, and IFC was also positively correlated with SSRT (P’s < 0.05). Beta band global efficiency was positively correlated with SSRT (P = 0.01).ConclusionThis is the first study to investigate the relationship between resting-state cortical beta oscillations and response inhibition. Our findings revealed that individuals with better ability of motor inhibitory control tend to have less cortical beta band power and functional connectivity. This study has clinical significance on the underlying mechanisms of motor inhibitory control deficits.

As an important type of hydrocarbon reservoir, microbial carbonate contains great amount of hydrocarbon resources. The recent discovery of industrial gas in the Majiagou Formation in the east-central part of the Ordos Basin indicates that this type of reservoir also has very extensive exploration prospects in the Ordos Basin. Similar reservoirs were also found on the southern margin of the basin, but no systematic research has been achieved. In this paper, petrological and geochemical anatomy of microbial carbonate reservoirs of the Pingliang Formation on the southern margin of the Ordos Basin were carried out. Results show that the study area developed a larger-scale microbial mound and beach complex than that in the basin, and the thickness can be more than 100 m. The microbial rock is mainly agglomerate limestone with dissolution pores. The microbial rock reservoir of the Pingliang Formation has experienced two stages of karsting, quasi-syngenesis and epigenesis, which are the key for the formation of reservoir, and there is oil and gas charging during the burial period. Among them, the quasi-syngenetic stage experienced a brief exposure, forming a large amount of irregular-shaped solution pores, and radial fibrous calcite pores filled in the early pores, with similar oxygen/carbon isotope and trace element contents such as Sr and Mg as the matrix calcite, it is then indicated that they were originated from seawater in the same period. During the epigenetic stage, the early solution pores expanded, forming a large number of fractures and cavities, accompanied by the filling of coarse-crystal calcite and mud, and some of the coarse crystalline calcite shows the characteristics of atmospheric precipitation. There is oil and gas charging during the burial period. There are bituminous residues in the present-day solution holes and fractures, and a large amount of liquid hydrocarbon-bearing inclusions can be observed in the calcite filling during the burial period. In summary, the microbial carbonate of the Pingliang Formation at the southern edge of the Ordos Basin, where both reservoir formation and hydrocarbon filling processes exist, is a potential exploration field.

In the process of dynamic Measurement While Drilling (MWD), the strong vibration and rapid rotation of the Bottom Hole Assembly (BHA) lead to multi-frequency and high-amplitude noise interference in the attitude measurement signal. The weak original signal and extremely low signal-to-noise ratio (SNR) are always the technical difficulties of dynamic MWD. To solve this problem, this paper uses the chaotic effect of the Duffing system, which takes the expression (−x3 + x5) as a nonlinear restoring force to detect the weak characteristic signal of downhole dynamic MWD. First of all, in order to meet the limit condition of the chaotic phase transition of the system output, the frequency value of the characteristic signal is reconstructed and transformed based on the variable scale theory. Then, in order to solve the influence of the initial phase of the characteristic signal on the detection accuracy, a detection model based on the array Duffing system is presented, and a frequency-detection scheme with all-phase coverage is given. Finally, another array Duffing system is designed for the parameter estimation of the characteristic signal. The critical value of chaotic phase transition is determined by adjusting the amplitude of the driving signal of the array Duffing system, and then the amplitude and phase parameters of the characteristic signal are synchronously estimated. The experimental results show that the proposed method can effectively extract the weak characteristic signal within the strong noise, and the SNR of the characteristic signal can be as low as −21 dB. Through the attitude calculation for the extracted characteristic signal, it can be seen that the proposed method can improve the accuracy of the inclination of the drilling tool significantly, which proves the feasibility and effectiveness of the method proposed in this paper.

Spatial crowdsourcing refers to the allocation of crowdsourcing workers to each task based on location information. K-nearest neighbor technology has been widely applied in crowdsourcing applications for crowdsourcing allocation. However, there are still several issues need to be stressed. Most of the existing spatial crowdsourcing allocation schemes operate on a centralized framework, resulting in low efficiency of crowdsourcing allocation. In addition, these spatial crowdsourcing allocation schemes are one-way allocation, that is, the suitable matching objects for each task can be queried from the set of crowdsourcing workers, but cannot query in reverse. In this article, a bidirectional k-nearest neighbor spatial crowdsourcing allocation protocol based on edge computing (BKNN-CAP) is proposed. Firstly, a spatial crowdsourcing task allocation framework based on edge computing (SCTAFEC) is established, which can offload all tasks to edge nodes in edge computing layer to realize parallel processing of spatio-temporal queries. Secondly, the positive k-nearest neighbor spatio-temporal query algorithm (PKNN) and reverse k-nearest neighbor spatio-temporal query algorithm (RKNN) are proposed to make the task publishers and crowdsourcing workers conduct two-way query. In addition, a road network distance calculation method is proposed to improve the accuracy of Euclidean distance in spatial query scenarios. Experimental results show that the proposed protocol has less time cost and higher matching success rate compared with other ones.

Summary: KRAS inhibitor AMG510 covalently modifies the G12C residue and inactivates the KRAS/G12C function. Because there are many reactive cysteines in the proteome, it is important to characterize AMG510 on-target modification and off-targets. Here, we presented a streamlined workflow to measure abundant AMG510 modified peptides including that of KRAS/G12C by direct profiling, and a pan-AMG510 antibody peptide IP workflow to profile less abundant AMG510 off-targets. We identified over 300 off-target sites with three distinct kinetic patterns, expanding the AMG510 modified proteome involved in the nucleocytoplasmic transport, response to oxidative stress, adaptive immune system, and glycolysis. We found that AMG510 covalently modified cys339 of ALDOA and inhibited its enzyme activity. Moreover, AMG510 modified KEAP1 cys288 and induced NRF2 accumulation in the nuclear of NSCLC cells independent of KRAS/G12C mutation. Our study provides a comprehensive resource of protein off-targets of AMG510 and elucidates potential toxicological sideeffects for this covalent KRASG12C inhibitor.

ObjectiveBased on the theoretical model for the “stress–sleep” relationship, this study investigated the impact of parental phubbing on adolescent sleep quality problems and a moderated mediation mechanism.MethodsA total of 781 adolescents was surveyed using the Chinese version of Parental Phubbing Scale, the Ultra-brief Screening Scale for Depression and Anxiety Scale, the Self-Control Questionnaire for Chinese children, and the Chinese version of Pittsburgh Sleep Quality Index Scale.ResultsParental phubbing and negative emotions were significantly and positively correlated to sleep quality problems, but self-control was not correlated to sleep quality problems. Parental phubbing directly influenced sleep quality problems and also indirectly influenced sleep quality problems through the mediating effect of negative emotions. Moreover, self-control played a moderating role in the path of parental phubbing affecting negative emotions. That is, the effect was more significant for adolescents low in self-control relative to those high in self-control.ConclusionParental phubbing is a risk factor for adolescent sleep quality problems. This study is the first to demonstrate empirical evidence for the relationship between parental phubbing and sleep quality problems.

BackgroundThe human insulin-like growth factor 2 mRNA binding proteins 1–3 (IGF2BP1–3, also called IMP1–3) play essential roles in mRNA regulation, including its splicing, translocation, stability, and translation. However, knowledge regarding the involvement of IGF2BPs in tumor immunity and stemness across cancer types is still lacking.MethodsIn this study, we comprehensively analyzed pan-cancer multi-omic data to determine the correlation of IGF2BPs mRNA and protein expression with various cancer parameters such as mutation frequency, prognostic value, the tumor microenvironment (TME), checkpoint blockade, tumor immune infiltration, stemness and drug sensitivity. Validation of the expression of IGF2BPs in cancer samples and glioma cells were performed by quantitative real-time (qRT)-PCR, and immunofluorescence staining. Investigation of the functional role of IGF2BP3 in glioma stem cells(GSCs) were performed by sphere formation, cytotoxicity, transwell, and wound healing assays.ResultsWe found that IGF2BP1 and 3 are either absent or expressed at very low levels in most normal tissues. However, IGF2BP1-3 can be re-expressed in a broad range of cancer types and diverse cancer cell lines, where their expression often correlates with poor prognosis. Immunofluorescence staining and qRT-PCR analyses also showed that the expression of IGF2BP2 and IGF2BP3 were higher in cancer tissues than that in adjacent normal tissues. Moreover, IGF2BPs are associated with TME and stemness in human pan-cancer. Remarkably, IGF2BP3 participated in the maintenance and self-renewal of glioma stem cell (GSCs). Knockdown of IGF2BP3 attenuated GSC and glioma cell proliferation, invasion, and migration.ConclusionsOur systematic pan-cancer study confirmed the identification of IGF2BPs as therapeutic targets and highlighted the need to study their association with stemness, and the TME, which contribute to the cancer drug-discovery research. Especially, preliminary studies demonstrate the IGF2BP3 as a potential negative regulator of glioma tumorigenesis by modulating stemness.

For concrete dams, the saturation level before freezing is an important factor influencing freeze-thaw deterioration of the downstream area of the dam. The integrated method of laboratory test-numerical inversion-feedback verification-engineering prediction was used to obtain concrete saturation levels at different depths within the concrete on the downstream zone of a dam under low-temperature conditions. First, tests were designed and carried out on capillary water absorption of unsaturated concrete under controlled and low-temperature conditions. Then, based on measured saturation levels in a controlled low-temperature environment, an optimization algorithm was used to identify key parameters in a capillary water absorption-water transport model for unsaturated concrete. Afterward, the measured saturation levels of previously unsaturated concrete under practical low-temperature conditions were utilized for feedback verification of the proposed model. Finally, the distribution of saturation levels of concrete on the downstream zone of a typical dam under low-temperature conditions was predicted. The study demonstrated in three geographic locations (northeast, northwest, and central China) that when the capillary water absorption before freezing continued for 5 d, 6 d, and 10 d, the saturation level of concrete on the downstream zone of a dam which exceeds 91.7 % was only near the water absorption surface for the sections of the dam. The critical depths within the concrete were 1.2 cm, 1.3 cm, and 1.8 cm at dams in northeast, northwest and central China, respectively.

BackgroundStroke is the second leading cause of death worldwide, with a large proportion of survivors suffering from motor dysfunction and neuropsychiatric sequelae. Repetitive transcranial magnetic stimulation (rTMS) is a promising stroke rehabilitation intervention and is effective in improving neurological system function in stroke patients. In the current systemic review and meta-analysis, an overview of the most recent studies regarding the effectiveness of rTMS's potential to help chronic stroke patients recover from sequelae was provided.MethodsRelevant randomized controlled trials were retrieved from three online databases (Web of Science, Medline, and Embase). A total of 25 RCTs (N = 535 participants) were included. A meta-analysis was performed using a fixed-effects model or a random-effects model, and effect sizes were reported as weighted mean differences or standardized mean differences.ResultsAdministration of rTMS significantly improved upper limb function, hand function, and muscle tone in stroke patients throughout the chronic phase [≥6 months], but not lower limb mobility and strength. In terms of cognitive function, rTMS has a considerable positive impact on patients' cognitive performance. rTMS also alleviated apathy in stroke patients more than post-stroke depressive symptoms regarding mental functioning. Balance and walking function, as well as functional activities of daily living, of patients were dramatically improved by rTMS. However, the current conclusions should be taken carefully due to the small sample size of the meta-analysis.ConclusionsThis is the first meta-analysis of rTMS treatment in patients with chronic stroke to inform the selection of the optimal treatment strategy for patients with chronic stroke, which demonstrated that rTMS treatment has the potential to improve the effects of sequelae by improving upper limb function, hand function, and muscle tone.Systematic review registrationhttps://inplasy.com/inplasy-2022-7-0095/, identifier: INPLASY202270095.

Colorectal cancer (CRC) is the third most common cancer in the world in terms of morbidity and mortality, which brings great health hazards and economic burdens to patients and society. A fecal examination is an effective method for clinical examination and the most commonly used method for the census. It is simple, non-invasive, and suitable for large-scale population screening. With the development of molecular biology, lots of efforts have been made to discover new fecal biomarkers for the early screening of colorectal cancer. In this review, we summarize and discuss the recent advances of fecal biomarkers for CRC screening or diagnosis, including DNA biomarkers, RNA biomarkers, protein biomarkers, gut microbes and volatile organic compounds focusing on their diagnostic evaluation for CRC, which can provide a basis for the further development of new and effective CRC fecal screening and early diagnosis techniques.

Abstract Ferroptosis is closely linked to various cancers, including lung adenocarcinoma (LUAD); however, the factors involved in the regulation of ferroptosis-related genes are not well established. In this study, we identified and characterized ferroptosis-related long noncoding RNAs (lncRNAs) in LUAD. In particular, a coexpression network of ferroptosis-related mRNAs and lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were performed to establish a prognostic ferroptosis-related lncRNA signature (FerRLSig). We obtained a prognostic risk model consisting of 10 ferroptosis-related lncRNAs: AL606489.1, AC106047.1, LINC02081, AC090559.1, AC026355.1, FAM83A-AS1, AL034397.3, AC092171.5, AC010980.2, and AC123595.1. High risk scores according to the FerRLSig were significantly associated with poor overall survival (hazard ratio (HR) = 1.412, 95% CI = 1.271–1.568; P

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a promising intervention for stroke rehabilitation. Several studies have demonstrated the effectiveness of rTMS in restoring motor function. This meta-analysis aimed to summarize the current evidence of the effect of rTMS in improving upper limb function and fine motor recovery in stroke patients.MethodsThree online databases (Web of Science, PubMed, and Embase) were searched for relevant randomized controlled trials. A total of 45 studies (combined n = 2064) were included. Random effects model was used for meta-analysis and effect size was reported as standardized mean difference (SMD).ResultsrTMS was effective in improving fine motor function in stroke patients (SMD, 0.38; 95% CI 0.19–0.58; P = 0). On subgroup analyses, for post-stroke functional improvement of the upper extremity, bilateral hemisphere stimulation was more effective than unilateral stimulation during the acute phase of stroke, and a regimen of 20 rTMS sessions produced greater improvement than 10 rTMS sessions. For the rTMS stimulation method, both TBS and rTMS were found to be significantly more effective in the acute phase of stroke, but TBS was more effective than rTMS. However, rTMS was found to be more effective than TBS stimulation in patients in the subacute and chronic phases of stroke. rTMS significantly improved upper limb and fine function in the short term (0–1-month post-intervention) and medium term (2–5 months), but not for upper limb function in the long term (6 months+). The results should be interpreted with caution due to significant heterogeneity.ConclusionsThis updated meta-analysis provides robust evidence of the efficacy of rTMS treatment in improving upper extremity and fine function during various phases of stroke.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-5-0121/, identifier: INPLASY202250121.

Objective To compare the clinical value of transcranial Doppler (TCD) ultrasound and computed tomography angiography (CTA) for diagnosing ischemic cerebrovascular disease. Methods A retrospective clinical study was conducted in 142 patients with ischemic cerebrovascular disease who were initially diagnosed by digital subtraction angiography. Under the single-blind condition, the patients were diagnosed by using TCD ultrasound and CTA independently. The accuracy of these two methods was compared. Results The accuracy of diagnosing bilateral middle cerebral artery, bilateral vertebral artery and bilateral internal carotid artery lesions with a TCD examination was significantly higher than that with a CTA examination. There were no significant differences in the accuracy of diagnosing bilateral anterior cerebral artery, bilateral posterior cerebral artery or basilar artery lesions between TCD ultrasound and CTA. The accuracy of diagnosing all cerebral arterial ischemic lesions was significantly higher with a TCD examination (87.39%) than with a CTA examination (69.75%). The accuracy of diagnosing all cerebral arteries that cause ischemic encephalopathy (cerebrovascular + cervical blood vessels) was significantly higher with a TCD examination (88.03%) than with a CTA examination (69.01%). Conclusions TCD ultrasound has several advantages over CTA. Therefore, TCD ultrasound is better for diagnosing ischemic encephalopathy than CTA.

Obesity and metabolic disorders have gradually become public health-threatening problems. The metabolic disorder is a cluster of complex metabolic abnormalities which are featured by dysfunction in glucose and lipid metabolism, and results from the increasing prevalence of visceral obesity. With the core driving factor of insulin resistance, metabolic disorder mainly includes type 2 diabetes mellitus (T2DM), micro and macro-vascular diseases, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and the dysfunction of gut microbiota. Strategies and therapeutic attention are demanded to decrease the high risk of metabolic diseases, from lifestyle changes to drug treatment, especially herbal medicines. Indole is a parent substance of numerous bioactive compounds, and itself can be produced by tryptophan catabolism to stimulate glucagon-like peptide-1 (GLP-1) secretion and inhibit the development of obesity. In addition, in heterocycles drug discovery, the indole scaffold is primarily found in natural compounds with versatile biological activity and plays a prominent role in drug molecules synthesis. In recent decades, plenty of natural or synthesized indole deriviatives have been investigated and elucidated to exert effects on regulating glucose hemeostasis and lipd metabolism. The aim of this review is to trace and emphasize the compounds containing indole scaffold that possess immense potency on preventing metabolic disorders, particularly T2DM, obesity and NAFLD, along with the underlying molecular mechanisms, therefore facilitate a better comprehension of their druggability and application in metabolic diseases.

Abstract Background An increase in blood flow in the forearm arteries has been reported after brachial plexus block (BPB). However, few studies have quantitatively analysed the blood flow of the forearm arteries after BPB or have studied only partial haemodynamic parameters. The purpose of the present study was to comprehensively assess blood flow changes in the distal radial artery (RA) and ulnar artery (UA) after BPB performed via a new costoclavicular space (CCS) approach using colour Doppler ultrasound. Methods Thirty patients who underwent amputated finger replantation and received ultrasound-guided costoclavicular BPB were included in the study. The haemodynamic parameters of the RA and UA were recorded before the block and 10 min, 20 min, and 30 min after the block using colour Doppler ultrasound to determine the peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (Vmean), pulsatility index (PI), resistance index (RI) and area. The volumetric flow rate (VFR) was calculated using the formula Q = area×Vmean. The aforementioned parameters were compared not only before and after the BPB but also between the RA and UA. Results Compared with those of the respective baselines, there was a significant increase in the PSV, EDV, Vmean, area, and VFR and a significant decrease in the PI and RI of the RA and UA 10 min, 20 min, and 30 min post-block. The increase 30 min post-block in EDV (258.68 % in the RA, 279.63 % in the UA) was the most notable, followed by that in the Vmean (183.36 % in the RA, 235.24 % in the UA), and the PSV (139.11 % in the RA, 153.15 % in the UA) changed minimally. The Vmean and VFR of the RA were significantly greater than those of the UA before the BPB; however, there was no significant difference in the VFR between the RA and UA after the BPB. Conclusions A costoclavicular BPB can increase blood flow in the forearm arteries. The RA had a higher volumetric flow rate than the UA before the BPB; however, the potential blood supply capacity of the UA was similar to that of the RA after a BPB. Trial registration This study was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/searchproj.aspx, clinical trial number: ChiCTR 1900023796, date of registration: June 12, 2019)

Abstract Chronic Infection of Hepatitis B virus (HBV) is one risk factor of hepatocellular carcinoma (HCC). Much effort has been made to research the process of HBV-associated HCC, but its molecular mechanisms of carcinogenesis remain vague. Here, weighted gene co-expression network analysis (WGCNA) was employed to explore the co-expressed modules and hub/key genes correlated to HBV-associated HCC. We found that genes of the most significant module related to HBV-associated HCC were enriched in DNA replication, p53 signaling pathway, cell cycle, and HTLV-1 infection associated pathway; these cellular pathways played critical roles in the initiation and development of HCC or viral infections. Furthermore, seven hub/key genes were identified based on the topological network analysis, and their roles in HCC were verified by expression and Kaplan-Meier survival analysis. Protein-protein interaction and KEGG pathway analysis suggested that these key genes may stimulate cellular proliferation to promote the HCC progression. This study provides new perspectives to the knowledge of the key pathways and genes in the carcinogenesis process of HBV-associated HCC, and our findings provided potential therapeutic targets and clues of the carcinogenesis of HBV-associated HCC.

Using a solid-state reaction strategy, nominal Li3TiO3F oxyfluorides ceramics were fabricated, and its sintering behavior, microstructure, phase assemblages, as well as microwave dielectric performances were all investigated. The main phase of Li3TiO3F with cubic structures accompanied with small amounts of the LiF or Li2TiO3 secondary phase was identified by XRD analysis. SEM analysis showed that a uniform and dense microstructure was obtained for 750 °C-sintered samples. The dielectric constant (εr) and quality factor (Q × f) were found to be strongly correlated with porosity and grain size distribution, whereas the temperature coefficient of resonance frequency (τf) was mainly dominated by the phase assemblages. In particular, the 750 °C-sintered Li3TiO3F samples exhibited good microwave dielectric performances: εr = 18, Q × f = 57,300 GHz (under 9.2 GHz), τf = −43.0 ppm/°C.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint damage and even permanent disability, seriously affecting patients’ quality of life. At present, the complete cure for RA is not achievable, only to relieve the symptoms to reduce the pain of patients. Factors such as environment, genes, and sex can induce RA. Presently, non-steroidal anti-inflammatory drugs, DRMADs, and glucocorticoids are commonly used in treating RA. In recent years, some biological agents have also been applied in clinical practice, but most have side effects. Therefore, finding new mechanisms and targets for treating RA is necessary. This review summarizes some potential targets discovered from the perspective of epigenetics and RA mechanisms.