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ABSTRACTHelicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A (cagA)-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP_0888, upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA, leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae, selectively enriched in the colons of H. pylori-pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium.IMPORTANCESimultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A (cagA). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies.

Lifelong learning is crucial for equipping the workforce to navigate a volatile, uncertain, complex, and ambiguous (VUCA) world. Despite its importance, resistance to enrolling in lifelong learning courses persists. This exploratory study examines the exposure to and engagement with government-sponsored courses among two distinct groups: individuals who opt for these courses and those who select alternative courses. We employed comparative statistical analysis to identify the primary factors influencing course awareness and selection. Our findings underscore the enduring influence of traditional media in promoting course awareness. Additionally, personal interest and availability of subsidies emerged as significant determinants of course selection. Based on these insights, we propose policy recommendations to enhance the effectiveness of these courses. This empirical study contributes to the understanding of the dynamics of lifelong learning in Singapore, providing valuable insights for policy and practice.

ObjectiveThere is limited evidence on which immunosuppressive agents produce the best outcomes for adult patients with steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS). This review compares the remission rate and adverse effects of various immunosuppressants used.MethodsStudies of adult patients with biopsy-proven SDNS/FRNS, administered any immunosuppressive agents and reported complete remission results as one of the clinical outcomes were included. Articles were independently screened by two researchers. ROBINS-I was used for risk of bias assessment. Random-effects model was used for statistical analysis and corresponding 95% confidence intervals (CIs) were calculated.Results574 patients across 28 studies were included in the analysis. Patients receiving rituximab have a complete remission rate of 89% (95% CI = 83% to 94%; τ2 = 0.0070; I2 = 62%; overall p < 0.01, low certainty) and adverse event rate of 0.26, cyclosporine (CR 40%; 95% CI = 21% to 59%; τ2 = 0.0205; I2 = 55%; overall p = 0.08, low certainty), tacrolimus (CR 84%; 95% CI = 70% to 98%; τ2 = 0.0060; I2 = 33%; overall p = 0.21, moderate certainty), mycophenolate mofetil (CR 82%; 95% CI = 74% to 90%; τ2 < 0.0001; I2 = 15%; overall p = 0.32, moderate certainty) and cyclophosphamide (CR 79%; 95% CI = 69% to 89%; τ2 = 0; I2 = 0%; overall p = 0.52, moderate certainty).ConclusionAmong the commonly used immunosuppressive agents, only rituximab has a statistically significant effect in achieving complete remission among patients with SDNS/FRNS and has a relatively good safety profile, but this is limited by low quality of evidence with high degree of heterogeneity causing a lack of statistical power.

Amidst the fourth industrial revolution, marked by swift technological advancements and changing economic environments, lifelong learning has risen as an essential cornerstone for developing people and society. Adult education, with a particular focus on skills learning, is vital in equipping individuals with the necessary competencies to navigate the dynamic demands of the modern workforce. This paper provides a qualitative analysis and commentary on the case study of Singapore’s SkillsFuture movement, an exemplary national initiative to promote skills learning among adults. Intending to reach a wide audience in educational science, we investigate the effectiveness and impact of this comprehensive programme and its implications for other countries. This article contributes to educational science and policy development by illustrating the importance of investing in adult education and skills development. By comprehensively studying the SkillsFuture experience, we offer valuable insights into establishing effective and inclusive lifelong learning ecosystems to foster a culture of continuous learning, equipping individuals to adapt and thrive in a volatile, uncertain, complex, and ambiguous global landscape.

Abstract A new 2D titanium carbide (Ti3C2), a low dimensional material of the MXene family has attracted remarkable interest in several electronic applications, but its unique structure and novel properties are still less explored in piezoelectric energy harvesters. Herein, a systematic study has been conducted to examine the role of Ti3C2 multilayers when it is incorporated in the piezoelectric polymer host. The 0.03 g/L of Ti3C2 has been identified as the most appropriate concentration to ensure the optimum performance of the fabricated device with a generated output voltage of about 6.0 V. The probable reasons might be due to the uniformity of nanofiller distribution in the polyvinylidene difluoride (PVDF) and the incorporation of Ti3C2 in a polymer matrix is found to enhance the β-phase of PVDF and diminish the undesired α-phase configuration. Low tapping frequency and force were demonstrated to scavenge electrical energy from abundant mechanical energy resources particularly human motion and environmental stimuli. The fabricated device attained a power density of 14 µW.cm−2 at 10.8 MΩ of load resistor which is considerably high among 2D material-based piezoelectric nanogenerators. The device has also shown stable electrical performance for up to 4 weeks and is practically able to store energy in a capacitor and light up a LED. Hence, the Ti3C2-based piezoelectric nanogenerator suggests the potential to realize the energy harvesting application for low-power electronic devices.

BackgroundContralateral axillary lymph node metastasis (CAM) is classified as distant metastasis in guidelines, but the prognosis is better than that of stage IV patients. It is controversial to classify CAM as a distant metastasis or a regional metastasis, and the optimal treatment strategy for CAM is unknown.Patients and MethodsBreast cancer patients who were confirmed by pathology and treated at Shandong Cancer Hospital between January 2012 and July 2021 were included in our study. We retrospectively reviewed the medical records of the patients for their clinical features, pathological diagnosis, treatment strategy, and follow-up data. Survival analysis was calculated by Kaplan–Meier analysis, and patient matching was performed by case–control matching.ResultsA total of 60 patients were included, and there were 49 metachronous CAM cases and 11 synchronous CAM cases. The prognosis of isolated CAM patients was better than that of patients with other distant metastases in terms of CAM-OS and PFS with significant differences (median CAM-OS 71.0 vs. 30.0 months, P=0.022; median PFS 42.0 vs. 11.0 months, P=0.009) and OS without significant differences (median OS 126.0 vs. 79.0 months, P=0.111). The five-year survival rate of isolated CAM patients was 67.4%, and the five-year disease-free survival (DFS) rate was 52.9%. The prognosis of CAM patients was similar to that of N3M0 patients in terms of OS (mean OS 82.4 vs. 65.6 months, P=0.537) and DFS (mean PFS 54.5 vs. 52.6 months, P=0.888). Axillary lymph node dissection (ALND) or low-middle level ALND significantly improved the OS (mean OS 237.4 vs. 111.0 months, P=0.011), CAM-OS (mean CAM-OS 105.2 vs. 46.6 months, P = 0.002), and PFS (mean PFS 92.3 vs. 26.9 months, P = 0.001) of isolated CAM patients. Axillary radiotherapy improved PFS, CAM-OS, and OS but without significant differences (mean PFS 80.0 vs. 46.6 months, P = 0.345; mean CAM-OS 86.8 vs. 72.1 months, P = 0.338; mean OS 147.6 vs. 133.0 months, P = 0.426).ConclusionCAM should be diagnosed as local recurrence and treated with aggressive and curative rather than palliative strategies. Contralateral axillary surgery and radiotherapy are recommended for isolated CAM patients.

Braconid parasitoids reared from Malus sieversii and Malus domestica trees in NW China infested by Agrilus mali Matsumura (Coleoptera, Buprestidae) are illustrated and discussed. Six species were found parasitising Agrilus mali in NW China, namely, Atanycolus ivanowi (Kokujev) (Braconinae), Doryctes undulatus (Ratzeburg), Pareucorystes varinervis Tobias, Polystenus rugosus Foerster, Spathius sinicus Chao, and Spathius brevicaudis Ratzeburg (Doryctinae). All listed species are newly recorded parasitoids of Agrilus mali. Pareucorystes varinervis and Spathius brevicaudis are new records for the Chinese fauna, but Spathius brevicaudis has been recorded from Taiwan before. Both sexes of Spathius brevicaudis are redescribed here to allow inclusion in the recent revision of the Chinese Spathius species. An identification key to the six braconid parasitoids of Agrilus mali in NW China is provided.

Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of severe invasive disease in neonate, elderly, and immunocompromised patients worldwide. Despite recent advances in the diagnosis and intrapartum antibiotic prophylaxis (IAP) of GBS infections, it remains one of the most common causes of neonatal morbidity and mortality, causing serious infections. Furthermore, recent studies reported an increasing number of GBS infections in pregnant women and elderly. Although IAP is effective, it has several limitations, including increasing antimicrobial resistance and late GBS infection after negative antenatal screening. Maternal immunization is the most promising and effective countermeasure against GBS infection in neonates. However, no vaccine is available to date, but two types of vaccines, protein subunit and capsular polysaccharide conjugate vaccines, were investigated in clinical trials. Here, we provide an overview of the GBS vaccine development status and recent advances in the development of immunoassays to evaluate the GBS vaccine clinical efficacy.

Abstract Poor permeation of therapeutic agents and multidrug resistance (MDR) in solid tumors are the two major challenges that lead to the failure of the current chemotherapy methods. Herein, a zero‐waste doxorubicin‐loaded heparin/folic acid/l‐arginine (HFLA‐DOX) nanomotor with motion ability and sustained release of nitric oxide (NO) to achieve deep drug penetration and effective reversal of MDR in cancer chemotherapy is designed. The targeted recognition, penetration of blood vessels, intercellular penetration, special intracellular distribution (escaping from lysosomes and accumulating in Golgi and nucleus), 3D multicellular tumor spheroids (3D MTSs) penetration, degradation of tumor extracellular matrix (ECM), and reversal of MDR based on the synergistic effects of the motion ability and sustained NO release performance of the NO‐driven nanomotors are investigated in detail. Correspondingly, a new chemotherapy mode called recognition‐penetration‐reversal‐elimination is proposed, whose effectiveness is verified by in vitro cellular experiments and in vivo animal tumor model, which can not only provide effective solutions to these challenges encountered in cancer chemotherapy, but also apply to other therapy methods for the special deep‐tissue penetration ability of a therapeutic agent.

Background: Blood flow restriction training (also known as KAATSU training) uses professional equipment to apply pressure to the base of the limbs to limit the blood flow at the distal end of the limbs during exercise, thereby stimulating muscle growth and improving muscle strength with a low exercise intensity. This study aimed to conduct a meta-analysis on the effects of blood flow restriction training on aerobic capacity. Methods: A systematic review and quantitative evidence synthesis (QES) was used to examine the effects of blood flow restriction training on the aerobic capacity. A literature search was performed on relevant databases. Search engines used were MEDLINE, EMBASE, PubMed, Web of Science, SPORT-Discus, CINHAL, ScienceDirect, and the Cochrane Library. Search terms were KAATSU training, blood flow restriction training, and occlusion training. Thirteen articles (a total sample size of 246 participants) fulfilled the inclusion criteria and were included. Results: Blood flow restriction training promoted the improvement in aerobic capacity (standard mean difference (SMD) = 0.40, 95% confidence interval (CI) (0.14–0.66), I2 = 0%, p < 0.01), showing no publication bias. In subgroup analysis, intervention methods, and intervention frequencies had different effects on aerobic capacity. Conclusions: Blood flow restriction training, which is a low intensity exercise, significantly affected aerobic capacity. Twelve blood flow restriction training sessions a week achieved significantly better results than a frequency of two to four training sessions per week. A daily blood flow restriction training session of 6 to 30 min significantly improved aerobic capacity.

Mycelium-bound composites are promising materials for sustainable packaging, insulation, fashion, and architecture. However, moulding is the main fabrication process explored to date, strongly limiting the ability to design the complex shapes that could widen the range of applications. Extrusion is a facile and low energy-cost process that has not yet been explored for mycelium-bound composites with design freedom and structural properties. In this study, we combine cheap, easily and commonly available agricultural waste materials, bamboo microfibres, chitosan, and mycelium from Ganodermalucidum, to establish a composite mixture that is workable, extrudable and buildable. We study the impact of bamboo fibre size, chitosan concentration, pH and weight ratio of bamboo to chitosan to determine the optimum growth condition for the mycelium as well as high mechanical stiffness. The resulting materials have thus low energy costs, are sustainable and can be shaped easily. The developed composition is promising to further explore the use of mycelium-bound materials for structural applications using agricultural waste.

Solar desalination is a renewable energy-driven method that produces freshwater from saline/brackish water. Conventional solar desalination units are equipped with an inclined transparent condensing plate placed over a feedwater basin containing saline water. The process is limited to a small quantity of production because of scattered solar irradiation and the unavailability of solar heat due to intermittent cloudy weather. In this study, a Fresnel lens has been used to concentrate solar energy onto a spot to increase the local temperature of feedwater and the evaporation rate. Flat Fresnel lenses on a double sloped passive solar still were used, where the focal points were adjusted to fall directly on the feedwater. The experiments were conducted for two different geometries and alongside the comparison between the conventional and the modified solar still; the number of Fresnel lenses was also varied. Saline solution with a concentration of 20,000 ppm was used as the feedwater. The research is aimed to be implemented for producing freshwater in the natural weather conditions of Malaysia. It was found that using two Fresnel lenses instead of a single large one gives a boost to the production of freshwater per unit solar irradiation by 39%. The produced water has a total dissolved solids (TDS) value of 37 ppm, which is well within the drinking water standard range according to the World Health Organization.

Faced with the problem of frequent slippage of the wheel-arm inspection robot in overhead high-voltage transmission lines, a magnetic linear drive method, based on high-voltage direct current (HVDC) magnetic field, is proposed: The ampere force of an enhanced HVDC magnetic field, generated by an innovatively arranged current-carrying coil, is used as the driving force for the traction robot, replacing the traditional wheel-arm driving method, thereby eliminating the slip. A physical model for the magnetic driving force is established, according to the characteristics of the magnetic field around the HVDC transmission line and the driving force requirements of the robot. The relationship between the magnetic driving force, the physical model size, and the number of coil windings is analyzed. The magnetic drive model is simulated using the COMSOL software version is 5.0. The simulation results of the magnetic drive force model are compared to theoretical calculations, proving the proposed method as correct. The magnetic drive device is constructed according to the proposed magnetic drive model and experiments are carried out. The results show that the magnetic drive device can provide enough traction to drive the robot motion, proving that the proposed magnetic linear drive method is technically feasible.

Additively manufactured tungsten and its alloys have been widely used for plasma facing components (PFCs) in future nuclear fusion reactors. Under the fusion process, PFCs experience a high-temperature exposure, which will ultimately affect the microstructural features, keeping in mind the importance of microstructures. In this study, microhardness and electron backscatter diffraction (EBSD) techniques were used to study the specimens. Vickers hardness method was used to study tungsten under different parameters. EBSD technique was used to study the microstructure and Kikuchi pattern of samples under different orientations. We mainly focused on selective laser melting (SLM) parameters and the effects of these parameters on the results of different techniques used to study the behavior of samples.

α-l-arabinofuranosidase is a subfamily of glycosidases involved in the hydrolysis of l-arabinofuranosidic bonds, especially in those of the terminal non-reducing arabinofuranosyl residues of glycosides, from which efficient glycoside hydrolases can be screened for the transformation of ginsenosides. In this study, the ginsenoside Rc-hydrolyzing α-l-arabinofuranosidase gene, BsAbfA, was cloned from Bacilus subtilis, and its codons were optimized for efficient expression in E. coli BL21 (DE3). The recombinant protein BsAbfA fused with an N-terminal His-tag was overexpressed and purified, and then subjected to enzymatic characterization. Site-directed mutagenesis of BsAbfA was performed to verify the catalytic site, and the molecular mechanism of BsAbfA catalyzing ginsenoside Rc was analyzed by molecular docking, using the homology model of sequence alignment with other β-glycosidases. The results show that the purified BsAbfA had a specific activity of 32.6 U/mg. Under optimal conditions (pH 5, 40 °C), the kinetic parameters Km of BsAbfA for pNP-α-Araf and ginsenoside Rc were 0.6 mM and 0.4 mM, while the Kcat/Km were 181.5 s−1 mM−1 and 197.8 s−1 mM−1, respectively. More than 90% of ginsenoside Rc could be transformed by 12 U/mL purified BsAbfA at 40 °C and pH 5 in 24 h. The results of molecular docking and site-directed mutagenesis suggested that the E173 and E292 variants for BsAbfA are important in recognizing ginsenoside Rc effectively, and to make it enter the active pocket to hydrolyze the outer arabinofuranosyl moieties at C20 position. These remarkable properties and the catalytic mechanism of BsAbfA provide a good alternative for the effective biotransformation of the major ginsenoside Rc into Rd.

The evolution, habitat, and lifestyle of the cryptic clade II of Escherichia, which were first recovered at low frequency from non-human hosts and later from external environments, were poorly understood. Here, the genomes of selected strains were analyzed for preliminary indications of ecological differentiation within their population. We adopted the delta bitscore metrics to detect functional divergence of their orthologous genes and trained a random forest classifier to differentiate the genomes according to habitats (gastrointestinal vs external environment). Model was built with inclusion of other Escherichia genomes previously demonstrated to have exhibited genomic traits of adaptation to one of the habitats. Overall, gene degradation was more prominent in the gastrointestinal strains. The trained model correctly classified the genomes, identifying a set of predictor genes that were informative of habitat association. Functional divergence in many of these genes were reflective of ecological divergence. Accuracy of the trained model was confirmed by its correct prediction of the habitats of an independent set of strains with known habitat association. In summary, the cryptic clade II of Escherichia displayed genomic signatures that are consistent with divergent adaptation to gastrointestinal and external environments.