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Abstract Background The respiratory chain plays a key role in the growth of Mycobacterium tuberculosis complex (MTBC). However, the exact regulatory mechanisms of this system still need to be elucidated, and only a few studies have investigated the impact of genetic mutations within the respiratory chain on MTBC transmission. This study aims to explore the impact of respiratory chain gene mutations on the global spread of MTBC. Results A total of 13,402 isolates of MTBC were included in this study. The majority of the isolates (n = 6,382, 47.62%) belonged to lineage 4, followed by lineage 2 (n = 5,123, 38.23%). Our findings revealed significant associations between Single Nucleotide Polymorphisms (SNPs) of specific genes and transmission clusters. These SNPs include Rv0087 (hycE, G178T), Rv1307 (atpH, C650T), Rv2195 (qcrA, G181C), Rv2196 (qcrB, G1250T), Rv3145 (nuoA, C35T), Rv3149 (nuoE, G121C), Rv3150 (nuoF, G700A), Rv3151 (nuoG, A1810G), Rv3152 (nuoH, G493A), and Rv3157 (nuoM, A1243G). Furthermore, our results showed that the SNPs of atpH C73G, atpA G271C, qcrA G181C, nuoJ G115A, nuoM G772A, and nuoN G1084T were positively correlated with cross-country transmission clades and cross-regional transmission clades. Conclusions Our study uncovered an association between mutations in respiratory chain genes and the transmission of MTBC. This important finding provides new insights for future research and will help to further explore new mechanisms of MTBC pathogenicity. By uncovering this association, we gain a more complete understanding of the processes by which MTBC increases virulence and spread, providing potential targets and strategies for preventing and treating tuberculosis.

Background: Acting as mediators in cell-matrix and cell-cell communication, matricellular proteins play a crucial role in cancer progression. Thrombospondins (TSPs), a type of matricellular glycoproteins, are key regulators in cancer biology with multifaceted roles. Although TSPs have been implicated in anti-tumor immunity and epithelial-mesenchymal transition (EMT) in several malignancies, their specific roles to colon cancer remain elusive. Addressing this knowledge gap is essential, as understanding the function of TSPs in colon cancer could identify new therapeutic targets and prognostic markers. Methods: Analyzing 1981 samples from 10 high-throughput datasets, including six bulk RNA-seq, three scRNA-seq, and one spatial transcriptome dataset, our study investigated the prognostic relevance, risk stratification value, immune heterogeneity, and cellular origin of TSPs, as well as their influence on cancer-associated fibroblasts (CAFs). Utilizing survival analysis, unsupervised clustering, and functional enrichment, along with multiple correlation analyses of the tumor-microenvironment (TME) via Gene Set Variation Analysis (GSVA), spatial localization, Monocle2, and CellPhoneDB, we provided insights into the clinical and cellular implications of TSPs. Results: First, we observed significant upregulation of THBS2 and COMP in colon cancer, both of which displayed significant prognostic value. Additionally, we detected a significant positive correlation between TSPs and immune cells, as well as marker genes of EMT. Second, based on TSPs expression, patients were divided into two clusters with distinct prognoses: the high TSPs expression group (TSPs-H) was characterized by pronounced immune and stromal cell infiltration, and notably elevated T-cell exhaustion scores. Subsequently, we found that THBS2 and COMP may be associated with the differentiation of CAFs into pan-iCAFs and pan-dCAFs, which are known for their heightened matrix remodeling activities. Moreover, THBS2 enhanced CAFs communication with vascular endothelial cells and monocyte-macrophages. CAFs expressing THBS2 (THBS2+ CAFs) demonstrated higher scores across multiple signaling pathways, including angiogenic, EMT, Hedgehog, Notch, Wnt, and TGF-β, when compared to THBS2- CAFs. These observations suggest that THBS2 may be associated with stronger pro-carcinogenic activity in CAFs. Conclusions: This study revealed the crucial role of TSPs and the significant correlation between THBS2 and CAFs interactions in colon cancer progression, providing valuable insights for targeting TSPs to mitigate cancer progression.

Highlights Recent progress on the applications of 2D materials in perovskite solar cells is discussed from the views of bottom interfaces, top interfaces, and electrodes. The roles of van der Waals heterojunction in enhancing the performance of perovskite solar cells are highlighted. The future directions and challenges in development of 2D materials-based perovskite solar cells are provided.

Aluminum oxide (Al2O3) ceramics have been widely utilized as circuit substrates owing to their exceptional performance. In this study, boron nitride microribbon (BNMR)/Al2O3 composite ceramics are prepared using spark plasma sintering (SPS). This study examines the effect of varying the amount of toughened phase BNMR on the density, mechanical properties, dielectric constant, and thermal conductivity of BNMR/Al2O3 composite ceramics while also exploring the mechanisms behind the toughening and increased thermal conductivity of the fabricated ceramics. The results showed that for a BNMR content of 5 wt%, BNMR/Al2O3 composite ceramics displayed more enhanced characteristics than pure Al2O3 ceramics. In particular, the relative density, hardness, fracture toughness, and bending strength were 99.95%±0.025%, 34.11±1.5 GPa, 5.42±0.21 MPa·m1/2, and 375±2.5 MPa, respectively. These values represent increases of 0.76%, 70%, 35%, and 25%, respectively, compared with the corresponding values for pure Al2O3 ceramics. Furthermore, during the SPS process, BNMRs are subjected to high temperatures and pressures, resulting in the bending and deformation of the Al2O3 matrix; this leads to the formation of special thermal pathways within it. The dielectric constant of the composite ceramics decreased by 25.6%, whereas the thermal conductivity increased by 45.6% compared with that of the pure Al2O3 ceramics. The results of this study provide valuable insights into ways of enhancing the performance of Al2O3-based ceramic substrates by incorporating novel BNMRs as a second phase. These improvements are significant for potential applications in circuit substrates and related fields that require high-performance materials with improved mechanical properties and thermal conductivities.

BackgroundSputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma.MethodsThis study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation.ResultsThe levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%).ConclusionThis study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.

Abstract Background Iron plays a crucial role in the growth of Mycobacterium tuberculosis (M. tuberculosis). However, the precise regulatory mechanism governing this system requires further elucidation. Additionally, limited studies have examined the impact of gene mutations related to iron on the transmission of M. tuberculosis globally. This research aims to investigate the correlation between mutations in iron-related genes and the worldwide transmission of M. tuberculosis. Results A total of 13,532 isolates of M. tuberculosis were included in this study. Among them, 6,104 (45.11%) were identified as genomic clustered isolates, while 8,395 (62.04%) were classified as genomic clade isolates. Our results showed that a total of 12 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, such as Rv1469 (ctpD, C758T), Rv3703c (etgB, G1122T), and Rv3743c (ctpJ, G676C). Additionally, seven SNPs, including Rv0104 (T167G, T478G), Rv0211 (pckA, A302C), Rv0283 (eccB3, C423T), Rv1436 (gap, G654T), ctpD C758T, and etgB C578A, demonstrated a positive correlation with transmission clades across different countries. Notably, our findings highlighted the positive association of Rv0104 T167G, pckA A302C, eccB3 C423T, ctpD C758T, and etgB C578A with transmission clades across diverse regions. Furthermore, our analysis identified 78 SNPs that exhibited significant associations with clade size. Conclusions Our study reveals the link between iron-related gene SNPs and M. tuberculosis transmission, offering insights into crucial factors influencing the pathogenicity of the disease. This research holds promise for targeted strategies in prevention and treatment, advancing research and interventions in this field.

To adapt to different transmission power and distances, we design a rate-compatible transmission protocol to realize different transmission rates for ultraviolet (UV) communication. We have designed ensembles based on low-density parity-check (LDPC) codes, incorporating various code lengths and rates working under different channel conditions. Furthermore, the direct sequence spreading technique is adopted to obtain different channel codes working in weaker channel conditions. Through simulating the frame error rate (FER) performance across various signal and background radiation intensities, we obtain a table of switching thresholds for channel coding under distinct channel conditions. Different from that for radio-frequency (RF) communication with only one parameter of signal-to-noise ratio (SNR), the switching threshold table is constructed based on the combination of two parameters for UV Communication, the signal intensity and background radiation intensity. We also propose adaptive coding with hybrid automatic retransmission requests based on the combination of signal intensity and background intensity. It is verified through simulation that our designed system shows larger throughput under varying channel conditions compared with channel coding with a fixed rate in UV Communication.

AbstractFood waste is a global challenge to sustainable development. Nevertheless, there is insufficient research on the issue at the consumption stage, especially in developing countries (e.g., Malaysia). To effectively ameliorate food waste, it is crucial to understand how internal cultural values and external social influences affect food waste reduction. Drawing upon 345 Malaysian respondents, this study finds that religiosity, subjective norm, information publicity and personal norm have important effects on consumers’ intention to reduce food waste. However, materialism does not significantly influence consumers’ food waste behaviour, which is inconsistent with prior research. These findings advanced our understanding of food waste among Malaysian consumers, which provides insights to governments and NGOs on how to solve the food waste challenge.

Abstract The large‐sized nanofilm‐constructed hierarchical porous SiO2 (LNCHPS) is successfully prepared by the dual templating approach and subsequently used as the support for g‐C3N4. A series of characterization techniques are conducted to evaluate the structure and property of the as‐prepared materials. The LNCHPS possesses two sets of explicated successive pass‐through macropores (0.5–1.0 µm) with large specific surface area. In addition, the macropore wall is constructed by uniform mesoporous nanofilms with the thickness ranging from 35 to 50 nm. Then, the photocatalytic property is investigated by degradations towards Rhodamine B (RhB) under simulated sunlight, in which experiments have been performed through controlling the g‐C3N4 loading contents, solution pH values, and photocatalyst dosages. The apparent rate constant of g‐C3N4/LNCHPS could reach 0.03 min−1 under optimum conditions, showing 6.0 times that of the bulk g‐C3N4. In addition, g‐C3N4/LNCHPS also exhibits significantly enhanced performance in H2 evolution (39.9 µmol h−1) compared to that of the bulk g‐C3N4. High light absorption and utilization, enhanced adsorption capability and quick electron hole separation can render this fine structure excellent photocatalytic performance. Our work enables a facile route for large‐scale preparation of g‐C3N4/LNCHPS for addressing the wastewater treatment and hydrogen energy production simultaneously.

Summary: Non-apoptotic regulated cell death (RCD) of tumor cells profoundly affects tumor progression and plays critical roles in determining response to immune checkpoint inhibitors (ICIs). Prognosis-distinctive HCC subtypes were identified by consensus cluster analysis based on the expressions of 507 non-apoptotic RCD genes obtained from databases and literature. Meanwhile, a set of bioinformatic tools was integrated to analyze the differences of the tumor immune microenvironment infiltration, genetic mutation, copy number variation, and epigenetics alternations within two subtypes. Finally, a non-apoptotic RCDRS signature was constructed and its reliability was evaluated in HCC patients’ tissues. The high-RCDRS HCC subgroup showed a significantly lower overall survival and less sensitivity to ICIs compared to low-RCDRS subgroup, but higher sensitivity to cisplatin, paclitaxel, and sorafenib. Overall, we established an RCDRS panel consisting of four non-apoptotic RCD genes, which might be a promising predictor for evaluating HCC prognosis, guiding therapeutic decision-making, and ultimately improving patient outcomes.

Abstract Background Colorectal cancer (CRC) is the third frequently diagnosed cancer with high incidence and mortality rate worldwide. Our previous report has demonstrated that circCOL1A1 (hsa_circ_0044556) functions as an oncogene in CRC, and Gene Ontology (GO) analysis has also revealed the strong association between circCOL1A1 and angiogenesis. However, the mechanism of circCOL1A1 or exosomal circCOL1A1 in CRC angiogenesis remains elusive. Methods Purified exosomes from CRC cells were characterized by nanoparticle tracking analyzing, electron microscopy and western blot. qRT-PCR, immunohistochemistry or western blot were employed to test the expression of circCOL1A1, EIF4A3, Smad pathway and angiogenic markers. Cell proliferation of HUVECs was monitored by CCK-8 assay. The migratory and angiogenic capabilities of HUVECs were detected by wound healing and tube formation assay, respectively. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down and FISH assays were used to detect the interactions among circCOL1A1, EIF4A3 and Smad2/3 mRNA. The in vitro findings were verified in xenograft model. Results CRC cell-derived exosomal circCOL1A1 promoted angiogenesis of HUVECs via recruiting EIF4A3. EIF4A3 was elevated in CRC tissues, and it stimulated angiogenesis of HUVECs through directly binding and stabilizing Smad2/3 mRNA. Moreover, exosomal circCOL1A1 promoted angiogenesis via inducing Smad2/3 signaling pathway in vitro, and it also accelerated tumor growth and angiogenesis in vivo. Conclusion CRC cell-derived exosomal circCOL1A1 promoted angiogenesis via recruiting EIF4A3 and activating Smad2/3 signaling.

In this paper, we address the almost sure stability problem of Caputo fractional-order switched linear systems with deterministic and stochastic switching signals (DS-CFLSs). Firstly, due to the non-locality and memory of fractional-order switched systems, an inequality is proposed to solve the difficulties in the discussion of stability. Then, for DS-CFLSs, a deterministic switching strategy is predesigned, and stochastic switching signals are generated by the Markov process. After that, for the globally asymptotic stability almost surely (GAS a.s.) and exponential stability almost surely (ES a.s.) of DS-CFLSs, some sufficient conditions are proposed by using the multi-Lyapunov function and probability analysis methods. Finally, some numerical examples show that our results are effective.

Aiming at the problem of path planning for autonomous underwater vehicle (AUV) to cope with the influence of obstacles and eddies in complex marine environments, a path planning method based on an improved salp swarm algorithm (ISSA) is proposed. Firstly, the motion model of the AUV and eddy current model are constructed, including the relationship between position, velocity, attitude, and control inputs. Secondly, the improved SSA is proposed, which introduces the Levy flight strategy to enhance the algorithm’s optimization seeking ability and adds a nonlinear convergence factor to enhance the convergence ability of the algorithm. The stability and robustness of the improved algorithm are verified by test functions. Finally, the ISSA is applied to AUV path planning, which optimizes the AUV travel distance, improves the search efficiency and accuracy, and avoids the local optimum of the algorithm. The ISSA enhances the adaptive ability and robustness of the algorithm by introducing a dynamic adjustment strategy and feedback mechanism. Experimental verification is carried out using a simulated marine environment. The results show that the ISSA is better than the traditional algorithm in terms of path length as well as algorithm stability, and can effectively improve the navigation performance of AUV.

Abstract The aqueous micro batteries (AMBs) are expected to be one of the most promising micro energy storage devices for its safe operation and cost‐effectiveness. However, the performance of the AMBs is not satisfactory, which is attributed to strong interaction between metal ions and the electrode materials. Here, the first AMBs are developed with NH4+ as charge carrier. More importantly, to solve the low conductivity and the dissolution during the NH4+ intercalation/extraction problem of perylene material represented by perylene‐3,4,9,10‐tetracarboxylic dianhydride (PTCDA), the Ti3C2Tx MXene with high conductivity and polar surface terminals is introduced as a conductive skeleton (PTCDA/Ti3C2Tx MXene). Benefitting from this, the PTCDA/Ti3C2Tx MXene electrodes exhibit ultra‐high cycle life and rate capability (74.31% after 10 000 galvanostatic chargedischarge (GCD) cycles, and 91.67 mAh g−1 at 15.0 A g−1, i.e., capacity retention of 45.2% for a 30‐fold increase in current density). More significantly, the AMBs with NH4+ as charge carrier and PTCDA/Ti3C2Tx MXene anode provide excellent energy density and power density, cycle life, and flexibility. This work will provide strategy for the development of NH4+ storage materials and the design of AMBs.

Summary: CircRNAs are implicated in colorectal cancer (CRC) development and progression. Protein O-fucosyltransferase 1 (POFUT1) plays an oncogenic role via activating Notch1 signaling in CRC. However, the roles of circPOFUT1, which is originated from POFUT1, have not been investigated. Our study showed circPOFUT1 was highly expressed in CRC tissues and cells. CircPOFUT1 enhanced the proliferation, migration and invasion of CRC cells, and promoted tumor growth and liver metastasis in vivo. It also reinforced stemness and chemoresistance of CRC cells. Mechanistically, circPOFUT1 regulated the function of E2F7 via sponging miR-653-5p, thereby transcriptionally inducing WDR66 expression and further promoting metastasis in CRC. On the other hand, circPOFUT1 promoted stemness and chemoresistance of CRC cells via stabilizing BMI1 in an IGF2BP1-dependent manner. In conclusion, circPOFUT1 fosters CRC metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1.

Carbon neutrality target triggers the acceleration of China's rural energy revolution and energy transition. It is an irreversible trend that coal will phase out Rural Household Energy Mix (RHEM) in the long run. Problem is how coal will phase down and phase out in an orderly, effective, fair and high-quality way. National rural household energy consumption of all types is reviewed and related carbon emission accounted to manifest the evolvement of coal’s role, status and impacts in China’s RHEM since 1949. Household-level survey carried out in rural Beijing has discovered problems and challenges in the phasing out coal due to policy enforcement. Exergy is further assessed and predicted. The future role and contribution of coal among RHEM is identified for outlining coal’s phase out path by considering the resilience, economy and differentiated bottlenecks of carbon-neutral RHEM from the three-dimensional perspective of exergy, base energy context and comparative comprehensive cost-benefit calculation of energy substitution. The conclusions are as follows: ① Per capita energy consumption and exergy demand will continue to increase in coming years, and the per capita electricity consumption peak in a full electrification mode of RHEM is conservatively estimated to be about 5 000 kW·h. ② In the long run, rural household energy electrification has the characters of carbon neutrality, renewability and marketization. The coal revolution in RHEM, pursuing an improved cleaner and affordable energy pattern, consists of sustainable energy replacing coal and coal replacing biomass fuels. Before rural green energy market fully developed, coal is still the “ballast” for rural energy security. ③ In accordance with regional differences, it is wise to resort to five sub-path combinations belonging to three coal phaseout paths, that is, coal neutrality (improved stove technology and let the coal be), coal substitution (including coal replacement of primary biomass; clean coal upgrading) and coal substituted (inclusive of voluntary and mandatory phaseout of coal). It is anticipated that rural residents will enjoy a modern carbon-neutral energy system with resilience and fairness in future China.

Abstract Background Monochorionic (MC) twins present a higher incidence of unfavorable clinical perinatal outcomes than dichorionic (DC) twins, often in association with placental vascular anastomosis. In this study, we profiled the umbilical cord plasma metabolomes of uncomplicated MC and DC twin pregnancies and related these to several offspring outcomes, previously associated with birthweight. Methods Umbilical vein blood samples were collected at birth from 25 pairs of uncomplicated MC twins and 24 pairs of uncomplicated DC twins. The samples were subjected to gas chromatography-mass spectrometry-based metabolomics. 152 metabolites were identified from the cord plasma samples of MC and DC twins. Partial least squares discriminant analysis and pathway analysis were performed to compare within DC/MC twin pairs and between DC and MC twins. A generalized estimating equation (GEE) model was utilized to explore the correlation between metabolic differences and birthweight discordance within and between twin pairs. Results Our study revealed clear differences between the metabolite profiles of umbilical cord plasma of MC and DC twins. Metabolite profiles in MC within twin pairs and DC within twin pairs were characterized by the differences in 2 − hydroxyglutaramic acid levels and nicotinamide levels, respectively. The metabolic pathways of GSH, tryptophan, and fatty acid metabolism, were significantly downregulated in MC twins compared to DC twins. In addition, the concentration of caffeine and decamethyl-cyclopentasiloxane (D5) was positively correlated with birthweight in MC and DC twins. Conclusion This study demonstrated that the altered metabolites in umbilical plasma made contributions to the different chorionicities between uncomplicated MC twins and DC twins. The chorionicity of twins seems to affect the metabolic cross-talk between co-twin pairs and be related to birthweight discordance of twins.

The microstructure evolution during the cold rolling and subsequent annealing of Alloy 800H was investigated. Two distinct rolling methods, unidirectional rolling and cross-rolling, were introduced. Cracks were observed in the cross-rolled plates, while such cracks did not appear in the unidirectionally rolled plates, which indicated better ductility during the unidirectional rolling process. The difference between the two different rolling methods was explained by the evolution of Schmit factors during the deformation. A higher volume fraction of large, deformed grains was observed in the cross-rolled plates than in the unidirectionally rolled plates. Abnormal grain growth was observed in the cross-rolled specimens after annealing while no abnormal grain growth was seen in the unidirectionally rolled ones. In addition, the recrystallization occurred faster in plates from unidirectional rolling than from cross-rolling.

Key errors of machine tools have a significant impact on their accuracy, however accurately and quickly measuring the geometric errors of machine tools is essential for key error identification. Fortunately, a quick and direct laser measurement method and system for 21 geometric errors of three linear axes of machine tools were proposed previously, which enables the measurement of all 21 geometric errors via a one-step installation and a three-step automated measurement process. Based on this, to efficiently identify the key error factors, this paper first utilizes the 21 geometric errors obtained from the proposed measurement system to evaluate the contribution of each error to the volumetric errors of machine tools, leading to the building of a 21-geometric-error sensitivity analysis model. Then, experiments are carried out on the vertical machining tool TH5656, and all 21 geometric errors are obtained in 5 min. After this, the volumetric error distribution in the machining workspace is mapped according to the relationship between the geometric errors and the machining errors, and the key error factors affecting the manufacturing and machining accuracy of the TH5656 are ultimately determined. Thus, this new method provides a way to quickly identify key errors of the three linear axes of machine tools, and offers guidance for the machine tool configuration design, machining technology determination, and geometric error compensation.

Abstract Background/aims To investigate the clinical situation, treatment methods, and clinical predictors of surgical intervention in children with magnetic foreign bodies in the digestive tract. Materials and methods From January 2019 to June 2022, we retrospectively analyzed the clinical data of 72 children who ingested magnetic foreign bodies inadvertently in our hospital, including their general information, admissions, clinical manifestations, and treatment methods, as well as pertinent literature and statistical data. Following software processing, univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors of this study. Results In this study, 16 patients (22.2%) were discharged smoothly following conservative treatment and 19 patients (26.4%) were cured by gastroscopy. The remaining 37 patients (51.4%) were underwent surgery, in which 26 cases developed gastrointestinal perforation. There were statistical differences between surgery group and non- surgery group in the days of eating by mistake, clinical manifestations (nausea and vomiting, intermittent abdominal pain, abdominal muscle tension) and movement trajectory by every 24-h radiograph (P

Abstract This paper investigates the adaptive neural network prescribed performance control problem for a class of dual switching nonlinear systems with time-delay. By using the approximation of neural networks (NNs), an adaptive controller is designed to achieve tracking performance. Another research point of this paper is tracking performance constraints which can solve the performance degradation in practical systems. Therefore, an adaptive NNs output feedback tracking scheme is studied by combining the prescribed performance control (PPC) and backstepping method. With the designed controller and the switching rule, all signals of the closed-loop system are bounded, and the tracking performance satisfies the prescribed performance.

Abstract Background Although immunotherapy is effective in improving the clinical outcomes of patients with bladder cancer (BC), it is only effective in a small percentage of patients. Intercellular crosstalk in the tumor microenvironment strongly influences patient response to immunotherapy, while the crosstalk patterns of plasma cells (PCs) as endogenous antibody-producing cells remain unknown. Here, we aimed to explore the heterogeneity of PCs and their potential crosstalk patterns with BC tumor cells. Methods Crosstalk patterns between PCs and tumor cells were revealed by performing integrated bulk and single-cell RNA sequencing (RNA-seq) and spatial transcriptome data analysis. A risk model was constructed based on ligand/receptor to quantify crosstalk patterns by stepwise regression Cox analysis. Results Based on cell infiltration scores inferred from bulk RNA-seq data (n = 728), we found that high infiltration of PCs was associated with better overall survival (OS) and response to immunotherapy in BC. Further single-cell transcriptome analysis (n = 8; 41,894 filtered cells) identified two dominant types of PCs, IgG1 and IgA1 PCs. Signal transduction from tumor cells of specific states (stress-like and hypoxia-like tumor cells) to PCs, for example, via the LAMB3/CD44 and ANGPTL4/SDC1 ligand/receptor pairs, was validated by spatial transcriptome analysis and associated with poorer OS as well as nonresponse to immunotherapy. More importantly, a ligand/receptor pair-based risk model was constructed and showed excellent performance in predicting patient survival and immunotherapy response. Conclusions PCs are an important component of the tumor microenvironment, and their crosstalk with tumor cells influences clinical outcomes and response to immunotherapies in BC patients. Graphical Abstract

Highlights The excellent performance of MoS2/PANI cathode is due to better conductivity and desolvation shielding. The self-charging zinc battery was successfully assembled that achieve deep self-discharge and long cycle life. The quasi solid state battery and battery module have excellent performance and practicability.

Objective: According to Traditional Chinese Medicine theory, spleen deficiency and phlegm-dampness syndrome (SDPDS) are caused by abnormal water metabolism in the body because of spleen dysfunction. The purpose of this article was to evaluate the efficacy of D-limonene (DL) in resolving phlegm in mice with SDPDS from the perspective of regulating the level of aquaporin 3 (AQP3). Methods: The model of SDPDS was induced in mice using the multifactor modeling method, which combines internal and external dampness. An artificial climate box was used to create a humid environment, whereas the irregular diet was caused by different feeding methods on odd-even days. The mice were divided into blank control, model group, DL low-dose, DL high-dose, and positive groups. The mice were modeled and treated for 7 day. Levels of gastrin and amylase (AMS) in the serum, mucus secretion in the trachea, and AQP3 in the tissue near the gastric cardia. Results: DL significantly reduced mucus secretion in the trachea (P < 0.001). It also increased the level of AMS in the serum (P < 0.01) and decreased the level of AQP3 in the gastric tissue (P < 0.01). Conclusions: Mice with SDPDS exhibited disturbed water metabolism and significantly increased AQP3 levels. DL can restore the levels of AQP3 and plays an important role in resolving phlegm. This study may also help expand the efficacy of natural drugs containing DL and improve the utilization of natural drug resources.

Background A prerequisite for applying short tandem repeat (STR) kits is obtaining population allele and/or haplotype frequencies and forensic parameters. Aim Firstly, we aimed to investigate the population data of 19 X-chromosomal STRs (X-STRs) included in the AGCU X19 STR kit in the Han people residing in Hubei Province, Central China, and the Zhuang people residing in the Guangxi Zhuang Autonomous Region of South China. Furthermore, we compared these population data with those for other Chinese populations. Subjects and methods In total, 509 unrelated Han males and 266 unrelated Zhuang males were genotyped using the AGCU X19 STR kit. Allele frequencies, haplotype frequencies, and forensic parameters were computed, and genetic differences among 15 Chinese populations were analysed. Results The 19 X-STRs showed a high power of discrimination and high mean chance of exclusion, whether calculated using allele or haplotype frequencies. Major differences were found between Han and Oroqen, Uyghur, Mongolian, Tibetan, Li, and Yi populations. Aberrant biallelic patterns at DXS10159, DXS10134, and DXS10079 and allelic dropouts at DXS10164 were observed. Conclusion The 19 X-STRs were highly polymorphic in the Hubei Han and Guangxi Zhuang populations, and the AGCU X19 STR kit was shown to be suitable for forensic casework.

Tumor heterogeneity remains a major challenge for disease subtyping, risk stratification, and accurate clinical management. Exosome-based liquid biopsy can effectively overcome the limitations of tissue biopsy, achieving minimal invasion, multi-point dynamic monitoring, and good prognosis assessment, and has broad clinical prospects. However, there is still lacking comprehensive analysis of tumor-derived exosome (TDE)-based stratification of risk patients and prognostic assessment for breast cancer with systematic dissection of biological heterogeneity. In this study, the robust corroborative analysis for biomarker discovery (RCABD) strategy was used for the identification of exosome molecules, differential expression verification, risk prediction modeling, heterogenous dissection with multi-ome (6101 molecules), our ExoBCD database (306 molecules), and 53 independent studies (481 molecules). Our results showed that a 10-molecule exosome-derived signature (exoSIG) could successfully fulfill breast cancer risk stratification, making it a novel and accurate exosome prognostic indicator (Cox P = 9.9E-04, HR = 3.3, 95% CI 1.6–6.8). Interestingly, HLA-DQB2 and COL17A1, closely related to tumor metastasis, achieved high performance in prognosis prediction (86.35% contribution) and accuracy (Log-rank P = 0.028, AUC = 85.42%). With the combined information of patient age and tumor stage, they formed a bimolecular risk signature (Clinmin-exoSIG) and a convenient nomogram as operable tools for clinical applications. In conclusion, as an extension of ExoBCD, this study conducted systematic analyses to identify prognostic multi-molecular panel and risk signature, stratify patients and dissect biological heterogeneity based on breast cancer exosomes from a multi-omics perspective. Our results provide an important reference for in-depth exploration of the ''biological heterogeneity - risk stratification - prognosis prediction''.

Early diagnosis and progression assessment are critical for the timely detection and treatment of gastric cancer (GC) patients. Identification of diagnostic biomarkers for early detection of GC represents an unmet clinical need, and how these markers further influence GC progression is explored rarely. We performed dynamic gene screening based on high-throughput data analysis from patients with precancerous lesions and early gastric cancer (EGC) and identified a 10-gene panel by the lasso regression model. This panel demonstrated good diagnostic performance in TCGA (AUC = 0.95, sensitivity = 86.67 %, specificity = 90.63 %) and GEO (AUC = 0.84, sensitivity = 91.67 %, specificity = 78.13 %) cohorts. Moreover, three GC subtypes were clustered based on this panel, in which cluster 2 (C2) demonstrated the highest tumor progression level with a high expression of 10 genes, showing a decreased tumor mutation burden, significantly enriched epithelial-mesenchymal transition hallmark and increased immune exclusion/exhausted features. Finally, the cell localization of these panel genes was explored in scRNA-seq data based on more than 40,000 cells. The 10-gene panel is expected to be a new clinical early detection signature for GC and may aid in progression assessment and personalized treatment of patients.

Nowadays, the development of green and smart ships has become a trend in the global shipping industry. Some countries such as Japan and Korea, as well as several European countries, have already made some progress and advantages. In recent years, China has issued a series of policies to encourage and support the development of green and smart ships. Beyond that, the demonstration of green and smart ships has been promoted along with the trend of larger-sized and standardized inland vessels. The Chinese status and plans of green technologies are summarized including air layer drag reduction, efficient propulsion, DC networking, and clean energy. Some smart technologies have also been illustrated, for instance, intelligent driving, intelligent engine rooms, energy efficiency, hulls, cargo control, and information integration. Smart ship technologies need to be fully validated in order to improve industrialization applications. In the shipping industry, the development and application of smart ship technology need international and inter-regional cooperation, so as to achieve much higher energy savings, ensure environmental protection, achieve collaborative intelligence, and ensure safety and reliability. In turn, this will aid economic advances worldwide.

(1) Background: Polygonatum cyrtonema is a medicinal plant, and its polysaccharides are used for immunomodulation and the treatment of hyperglycemia. Investigation of the tissue distribution and pharmacokinetics of P. cyrtonema polysaccharide can further elucidate its pharmacological mechanisms. (2) Methods: A fluorescence-labeling approach using rhodamine B (RhB) as a fluorescent molecular probe was used for the quantitative assessment of the polysaccharide from dried P. cyrtonema (DPC1) samples, and the pharmacokinetics and tissue distribution of DPC1 were evaluated in mice after intraperitoneal or oral administration. (3) Results: DPC1 was successfully labeled with RhB, showing degrees of fluorescence labeling at 0.453% and 0.568% as determined by the ultraviolet and enzyme marker methods, respectively. DPC1-RhB was rapidly absorbed into the bloodstream after oral and intraperitoneal administration. Pharmacokinetic characteristics showed that oral administration and intraperitoneal administration were consistent with the features of a two-compartment model. (4) Conclusion: After administration, DPC1-RhB was primarily distributed in the tissues of the heart, spleen, and lung, indicating that the drug has a targeted effect on these tissues. Overall, the findings provide a comprehensive reference for the in vivo distribution of DPC1, together with a foundation for further elucidation of its pharmacological mechanisms and the development and application of DPC1 formulations.

Abstract The remarkable control function over the functional material formation process enabled by droplet microfluidic emulsification approaches can lead to the efficient and one‐step encapsulation of active substances in microparticles, with the microparticle characteristics well regulated. In comparison to the conventional fabrication methods, droplet microfluidic technology can not only construct microparticles with various shapes, but also provide excellent templates, which enrich and expand the application fields of microparticles. For instance, intersection with disciplines in pharmacy, life sciences, and others, modifying the structure of microspheres and appending functional materials can be completed in the preparation of microparticles. The as‐prepared polymer particles have great potential in a wide range of applications for chemical analysis, heavy metal adsorption, and detection. This review systematically introduces the devices and basic principles of particle preparation using droplet microfluidic technology and discusses the research of functional microparticle formation with high monodispersity, involving a plethora of types including spherical, nonspherical, and Janus type, as well as core–shell, hole–shell, and controllable multicompartment particles. Moreover, this review paper also exhibits a critical analysis of the current status and existing challenges, and outlook of the future development in the emerging fields has been discussed.

IntroductionObesity and diabetes are common chronic metabolic disorders which can cause an imbalance of the intestinal flora and gut-liver metabolism. Several studies have shown that probiotics, including Escherichia coli Nissle 1917 (EcN), promote microbial balance and metabolic health. However, there are no studies on how EcN outer membrane vesicles (EcN-OMVs) influence the intestinal microflora and affect the metabolic disorders of obesity and diabetes.MethodsIn this study, we evaluated the effects of EcN-OMVs on high-fat diet (HFD)-induced obesity and HFD + streptozotocin (STZ)-induced diabetes.ResultsEcN-OMVs could reduce body weight, decrease blood glucose, and increase plasma insulin in obese mice. Similarly, EcN-OMVs treatment could modify the ratio of Firmicutes/Bacteroidetes in the gut, elevate intestinal short-chain fatty acid (SCFA)-producing flora, and influence the SCFA content of the intestine. Furthermore, the intestinal metabolites ornithine and fumaric acid, hepatic ω-6 unsaturated fatty acids, and SCFAs were significantly increased after administering EcN-OMVs.DiscussionOverall, this study showed that EcN-OMVs might act as post-biotic agents that could modulate gut-liver metabolism and ameliorate the pathophysiology of obesity and diabetes.

There has been some controversy over the use of radiobiological models when modeling the dose-response curves of ionizing radiation (IR)-induced chromosome aberration and tumor prevalence, as those curves usually show obvious non-targeted effects (NTEs) at low doses of high linear energy transfer (LET) radiation. The lack of understanding the contribution of NTEs to IR-induced carcinogenesis can lead to distinct deviations of relative biological effectiveness (RBE) estimations of carcinogenic potential, which are widely used in radiation risk assessment and radiation protection. In this work, based on the initial pattern of two classes of IR-induced DNA double-strand breaks (DSBs) clustering in chromatin domains and the subsequent incorrect repair processes, we proposed a novel radiobiological model to describe the dose-response curves of two carcinogenic-related endpoints within the same theoretical framework. The representative experimental data was used to verify the consistency and validity of the present model. The fitting results indicated that, compared with targeted effect (TE) and NTE models, the current model has better fitting ability when dealing with the experimental data of chromosome aberration and tumor prevalence induced by multiple types of IR with different LETs. Notably, the present model without introducing an NTE term was adequate to describe the dose-response curves of IR-induced chromosome aberration and tumor prevalence with NTEs in low-dose regions. Based on the fitting parameters, the LET-dependent RBE values were calculated for three given low doses. Our results showed that the RBE values predicted by the current model gradually decrease with the increase of doses for the endpoints of chromosome aberration and tumor prevalence. In addition, the calculated RBE was also compared with those evaluated from other models. These analyses show that the proposed model can be used as an alternative tool to well describe dose-response curves of multiple carcinogenic-related endpoints and effectively estimate RBE in low-dose regions.

Ferroptosis is cell death caused by lipid peroxidation and plasma membrane rupture. Here, the authors report an additional role for the lipid flippase SLC47A1 as a regulator of lipid remodeling and survival during ferroptosis, thereby providing a metabolic target for overcoming drug resistance.

Abstract Dual switching system is a special hybrid system that contains both deterministic and stochastic switching subsystems. Due to its complex switching mechanism, few studies have been conducted for dual switching systems, especially for systems with uncertainty. Usually, the stochastic subsystems are described as Markov jump systems. Based upon the upstanding identity of RBF neural network on approaching nonlinear data, the tracking models for uncertain subsystems are constructed and the neural network adaptive controller is designed. The global asymptotic stability almost surely (GAS a.s.) and almost surely exponential stability (ES a.s.) of dual switching nonlinear error systems are investigated by using the energy attenuation theory and Lyapunov function method. An uncertain dual switching system with two subsystems, each with two modes, is studied. The uncertain functions of the subsystems are approximated well, and the approximation error is controlled to be below 0.05. Under the control of the designed adaptive controller and switching rules, the error system can obtain a good convergence rate. The tracking error is quite small compared with the original uncertain dual switching system.

The KP15 nanowires with one-dimensional properties has a defect-free surface, high anisotropy, and carrier mobility which is desirable for the development of novel nanodevices. However, the preparation of nanoscale KP15 is still inefficient. In this work, the Hansen solubility parameters of KP15 were first obtained. Based on the Hansen's empirical theory, the concentration of liquid-exfoliated KP15 nanowires was improved to 0.0458 mg·mL−1 by a solution containing 50% water and 50% acetone. Approximately 79% of the KP15 nanowires had a thickness value below 50 nm and 60.9% of them had a width value below 100 nm. The thinnest KP15 nanowires reached 5.1 nm and had smooth boundaries. Meanwhile, strong temperature-dependent Raman response in exfoliated KP15 nanowires has been observed, which indicates a strong phonon–phonon coupling in those nanowires. This is helpful for non-invasive temperature measurements of KP15 nanodevices.

Abstract Background Tuberculosis (TB) is one of the main infectious diseases that seriously threatens global health, while diagnostic delay (DD) and treatment dramatically threaten TB control. Methods Between 2005 and 2017 in Shandong, China, we enrolled pulmonary tuberculosis (PTB) patients with DD. DD trends were evaluated by Joinpoint regression, and associations between PTB patient characteristics and DD were estimated by univariate and multivariate logistic regression. The influence of DD duration on prognosis and sputum smear results were assessed by Spearman correlation coefficients. Results We identified 208,822 PTB cases with a median DD of 33 days (interquartile range (IQR) 18–63). The trend of PTB with DD declined significantly between 2009 and 2017 (annual percent change (APC): − 4.0%, P = 0.047, 2009–2013; APC: − 6.6%, P = 0.001, 2013–2017). Patients aged > 45 years old (adjusted odds ratio (aOR): 1.223, 95% confidence interval (CI) 1.189–1.257, 46–65 years; aOR: 1.306, 95% CI 1.267–1.346, > 65 years), farmers (aOR: 1.520, 95% CI 1.447–1.596), and those with a previous treatment history (aOR: 1.759, 95% CI 1.699–1.821) were prone to developing long DD (> 30 days, P

The Covid-19 pandemic has had an adverse effect on the global economy, particularly the hotel industry. Industry players have turned to big data to recover and improve their business performance. This paper aims to identify the key resources to develop and build big data analytics capabilities (BDAC). Drawing upon the knowledge-based and dynamic capability views, this research also examines the interplay among BDAC, organizational agility, marketing and organizational innovations, and firm performance in the hotel industry. The partial least square structural equation modeling is used for the data analysis, while quota sampling is used for the sampling design. Based on the statistical data analysis from 115 star-rated hotels in Malaysia, BDAC positively impacts organizational agility, marketing and organizational innovations, and firm performance. Likewise, organizational agility positively impacts firm performance, marketing and organizational innovations. The empirical findings provide researchers and industry players with meaningful insights for improving firm performance in the hotel industry using big data.

Abstract Background The pentose phosphate pathway (PPP) is an important mechanism by which tumour cells resist stressful environments and maintain malignant proliferation. However, the mechanism by which the PPP regulates these processes in colorectal cancer (CRC) remains elusive. Methods Closely related PPP genes were obtained from the TCGA and GEO databases. The effect of ATP13A2 on CRC cell proliferation was evaluated by performing in vitro assays. The connection between the PPP and ATP13A2 was explored by assessing proliferation and antioxidative stress. The molecular mechanism by which ATP13A2 regulates the PPP was investigated using chromatin immunoprecipitation and dual luciferase experiments. The clinical therapeutic potential of ATP13A2 was explored using patient‐derived xenograft (PDX), patient‐derived organoid (PDO) and AOM/DSS models. Findings We identified ATP13A2 as a novel PPP‐related gene. ATP13A2 deficiency inhibited CRC growth and PPP activity, as manifested by a decrease in the levels of PPP products and an increase in reactive oxygen species levels, whereas ATP13A2 overexpression induced the opposite effect. Mechanistically, ATP13A2 regulated the PPP mainly by affecting phosphogluconate dehydrogenase (PGD) mRNA expression. Subsequent studies showed that ATP13A2 overexpression promoted TFEB nuclear localization by inhibiting the phosphorylation of TFEB, thereby enhancing the transcription of PGD and ultimately affecting the activity of the PPP. Finally, ATP13A2 knockdown inhibited CRC growth in PDO and PDX models. ATP13A2−/− mice had a lower CRC growth capacity than ATP13A2+/+ in the AOM/DSS model.Our findings revealed that ATP13A2 overexpression‐driven dephosphorylation of TFEB promotes PPP activation by increasing PGD transcription, suggesting that ATP13A2 may serve as a potential target for CRC therapy.

Plant phenolic compounds have attracted considerable attention because of their health benefits. This study aimed to investigate the composition and antioxidant activity of phenol extracts from Polygonatum zanlanscianense Pamp. steam and leaf (PPP). The FTIR, UPLC-Q-Obtrip-MS, and HPLC−DAD methods were used to analyze the composition of PPP, and 20 phenolic compounds were preliminarily identified. Among them, the contents of hyperin, astragalin, and diosmetin levels were the highest. Treatment with PPP can significantly reduce t-BHP-induced cell damage in HepG2 cells, reactive oxygen species (ROS) accumulation, and malondialdehyde (MDA) content. Meanwhile, the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH−Px) activities can be increased. Moreover, PPP enhanced Nrf2 expression, which was consistent with that of heme oxygenase-1 (HO−1), glutamate–cysteine ligase catalytic subunit (GCLC), and NAD(P)H quinone oxidoreductase-1 (NQO1), whereas the expression of Keap1, the Nrf2 inhibitor, was decreased. All findings indicate that PPP can serve as a natural bioactive substance for preventing oxidative stress.

Abstract Background This study aims to construct a reliable diagnostic model for coronary artery disease (CAD) patients and explore its potential mechanism by consensus molecular subtypes of ferroptosis-related genes. Methods GSE12288 and GSE20680 were downloaded from Gene Expression Omnibus database. CAD patients were divided into different molecular subtypes according to the expression level of ferroptosis-related genes. Then, the distribution of differentially expressed genes, functional annotations and immune infiltration cells between the two subtypes were compared. Finally, a prognostic model of ferroptosis-related genes in CAD was constructed and verified. Results Two different molecular subtypes of CAD were obtained according to the expression level of ferroptosis-related genes. Then, a total of 1944 differentially expressed genes (DEGs) were found, among which, 236 genes were up-regulated and 1708 genes were down-regulated. In addition, 43 DEGs were ferroptosis-related genes. Functional enrichment analysis showed that these DEGs between two subtypes of CAD were mainly enriched in immune-related pathways and processes, such as T cell receptor, mTOR, NOD-like receptor and Toll-like receptor signaling pathways. We also found that 21 immune cells were significantly changed between two subtypes of CAD. The LASSO method was performed to identify and construct the 16 ferroptosis-related genes-based diagnostic signature. Diagnostic efficiency of diagnostic signature measured by AUC in the training set and validation cohort was 0.971 and 0.899, respectively. Conclusions This study contributes to a more comprehensive understanding of the mechanism of ferroptosis-related genes in CAD.

Drawing on previous literature on dynamic capability view (DCV), we examine the effects of data analytics capabilities (BDAC) on organizational ambidexterity and the paradoxical tensions between exploration and exploitation in the Malaysian banking sector. Although banks are often considered as mature commercial organizations, they are not free of issues concerning technological advancement and organizational changes for long-term competitiveness. Through statistical analysis by using data from 162 bank managers in Malaysia, it is confirmed that BDAC positively influences the two contradictory aspects of organizational ambidexterity (i.e., explorative dynamic capabilities and exploitative dynamic capabilities), and explorative dynamic capabilities also mediate the positive relationship between BDAC and exploitative marketing capabilities. The findings provide meaningful insights to researchers and bank managers on how to obtain sustainable competitive advances in the current digital era.

Abstract Background Previous studies have shown that the N6-methyladenosine (m6A) modification enhances the binding ability of mRNAs/long noncoding RNAs (lncRNAs) to microRNAs (miRNAs), but the impact of this modification on the competitive endogenous RNA (ceRNA) function of circular RNAs (circRNAs) is unclear. Methods We used a human circRNA microarray to detect the expression profiles of circRNAs in 3 pairs of cancer and paracancerous tissues from patients with colorectal cancer (CRC) and 3 pairs of peripheral blood specimens from patients with CRC and healthy individuals. The circRNAs highly expressed in both peripheral blood and tumour tissues of patients with CRC, including circALG1, were screened. A quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis of an expanded sample size was performed to detect the expression level of circALG1 in peripheral blood and tumour tissues of patients with CRC and determine its correlation with clinicopathological features, and circRNA loop-forming validation and stability assays were then conducted. Transwell assays and a nude mouse cancer metastasis model were used to study the function of circALG1 in CRC and the role of altered m6A modification levels on the regulation of circALG1 function. qRT-PCR, western blot (WB), Transwell, RNA-binding protein immunoprecipitation (RIP), RNA antisense purification (RAP), and dual-luciferase reporter gene assays were performed to analyse the ceRNA mechanism of circALG1 and the effect of the m6A modification of circALG1 on the ceRNA function of this circRNA. Results CircALG1 was highly expressed in both the peripheral blood and tumour tissues of patients with CRC and was closely associated with CRC metastasis. CircALG1 overexpression promoted the migration and invasion of CRC cells, and circALG1 silencing and reduction of the circALG1 m6A modification level inhibited CRC cell migration and invasion. In vivo experiments further confirmed the prometastatic role of circALG1 in CRC. Further mechanistic studies showed that circALG1 upregulated the expression of placental growth factor (PGF) by binding to miR-342-5p and that m6A modification enhanced the binding of circALG1 to miR-342-5p and promoted its ceRNA function. Conclusion M6A modification enhances the binding ability of circALG1 to miR-342-5p to promote the ceRNA function of circALG1, and circALG1 could be a potential therapeutic target in and a prognostic marker for CRC.

Abstract Background Mesenchymal stem cells (MSCs) are emerging as the mainstay of regenerative medicine because of their ability to differentiate into multiple cell lineages. The infinite proliferative potential of human pluripotent stem cells (PSCs) grants an unlimited supply of MSCs. Despite their great potential in therapeutic applications, several drawbacks have hindered its clinical translation, including limited number of replication, compromised potential and altered function in late passages. The aim of this study is to establish an efficient method for the production of MSCs from pluripotent stem cells for potential clinical application in rare human disease Hutchinson-Gilford progeria syndrome. Results We established a robust method allowing rapid derivation of MSCs from both human iPSCs and ESCs via a temporal induction of neural ectoderm in chemically defined media. The iPSC- and ESC-derived MSCs satisfy the standard criteria of surface markers. They exhibited a high tri-lineage differentiation potential with over 90% transcriptional similarity to the primary MSCs derived from bone marrow. To evaluate the potential application of this method in disease modeling, MSCs were generated from iPSCs derived from a patient with Hutchinson-Gilford progeria syndrome (HGPS-MSCs) and from mutation-rectified HGPS-iPSCs (cHGPS-MSCs). HGPS-MSCs manifested accelerated senescence whereas mutation rectification rescued cellular senescence in HGPS-MSCs. Conclusions The robust method of MSC derivation from ESCs and iPSCs provides an efficient approach to rapidly generate sufficient MSCs for in vitro disease modeling and clinical applications.

Abstract The RNA binding protein PTBP3 was recently reported to play a critical role in multiple cancers, and the molecular mechanisms involved RNA splicing, 3′ end processing and translation. However, the role of PTBP3 in colorectal cancer (CRC) remains poorly explored. Herein, PTBP3 was upregulated in CRC and associated with a poor prognosis. PTBP3 knockdown in colorectal cancer cell lines restricted CRC proliferative capacities in vitro and in vivo. Mechanistically, PTBP3 regulated the expression of the E3 ubiquitin ligase UBE4A by binding the 3′ UTR of its mRNA, preventing its degradation. UBE4A participated in P53 degradation, and PTBP3 knockdown in colorectal cancer cell lines showed increased P53 expression. UBE4A overexpression rescued PTBP3 knockdown-induced inhibition of CRC cell proliferation and P53 expression. Our results demonstrated that PTBP3 plays an essential role in CRC cell proliferation by stabilizing UBE4A to regulate P53 expression and may serve as a new prognostic biomarker and effective therapeutic target for CRC.

This paper mainly proposes some improved stochastic gradient descent (SGD) algorithms with a fractional order gradient for the online optimization problem. For three scenarios, including standard learning rate, adaptive gradient learning rate, and momentum learning rate, three new SGD algorithms are designed combining a fractional order gradient and it is shown that the corresponding regret functions are convergent at a sub-linear rate. Then we discuss the impact of the fractional order on the convergence and monotonicity and prove that the better performance can be obtained by adjusting the order of the fractional gradient. Finally, several practical examples are given to verify the superiority and validity of the proposed algorithm.

Respiratory syncytial virus (RSV) infection can cause life-threatening pneumonia and bronchiolitis, posing a significant threat to human health worldwide, especially to children and the elderly. Currently, there is no specific treatment for RSV infection. The most effective measures for preventing RSV infection are vaccines and prophylactic medications. However, not all population groups are eligible for the approved vaccines or antibody-based preventive medications. Therefore, there is an urgent need to develop novel vaccines and prophylactic drugs available for people of all ages. High-throughput assays that evaluate the efficacy of viral entry inhibitors or vaccine-induced neutralizing antibodies in blocking RSV entry are crucial for evaluating vaccine and prophylactic drug candidates. We developed an efficient entry assay using a lentiviral pseudovirus carrying the fusion (F) protein of type A or B RSV. In addition, the essential parameters were systematically optimized, including the number of transfected plasmids, storage conditions of the pseudovirus, cell types, cell numbers, virus inoculum, and time point of detection. Furthermore, the convalescent sera exhibited comparable inhibitory activity in this assay as in the authentic RSV virus neutralization assay. We established a robust pseudovirus-based entry assay for RSV, which holds excellent promise for studying entry mechanisms, evaluating viral entry inhibitors, and assessing vaccine-elicited neutralizing antibodies against RSV.