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Abstract Background Effective clinical communication skills are essential for dietitians as it impacts patient outcomes and satisfaction across diverse clinical and public healthcare settings. Despite its importance as a core competency, many dietetics programs, including those in Taiwan, need to provide sufficient training in this area. This study aimed to develop and assess a scenario-based simulation course to improve communication skills in dietetic students. Methods A non-randomized control group pretest–posttest design was used. The intervention consisted of a 12-week scenario-based simulation communication course divided into three units employing diverse teaching methods. One hundred nineteen third-year dietetic students from two universities were enrolled through convenience sampling, with 59 students in the experimental group and 60 in the control group. The experimental group participated in the course intervention, whereas the control group received no clinical communication skills training. Effectiveness was assessed by comparing participants' self-assessment of communication skills and Objective Structured Clinical Examination (OSCE) scores before and after the intervention and collecting feedback on learning satisfaction. Data were analyzed using paired t-tests and ANCOVA. Results The results showed that the post-test scores of the experimental group were significantly higher than those of the control group in terms of self-assessed clinical communication confidence, self-efficacy, and competence after controlling for pre-test scores. In the experimental group, the post-test OSCE scores were significantly higher than the pre-test scores, except for one item related to the nutrition assessment of diabetes. The intervention course's average learning satisfaction score was above 4.4 (out of 5 points). Conclusions This course effectively enhanced dietetic students’ clinical communication confidence, self-efficacy, and communication skills. These results can provide a reference for integrating clinical communication courses into undergraduate dietetics curricula.

ABSTRACT: Probiotics and synbiotics can mitigate the negative health consequences of early-life antibiotic exposure. This study aimed to determine whether supplementation with Bifidobacterium longum ssp. infantis 79 (B79) or synbiotics composed of B79 and 2′-fucosyllactose (2′-FL) could mitigate the negative impact of ceftriaxone exposure in early life. We found that antibiotic-treated mice exhibited lower BW, crypt depth, short-chain fatty acid content, and α-diversity indices at weaning, whereas they had increased relative abundance of opportunistic pathogens (such as Enterococcus and Staphylococcus) and decreased relative abundance of intestinal commensal bacteria. Supplementation with B79 and 2′-FL revived these antibiotic-induced negative effects and reduced the mRNA expression of IL-6, IL-12p40, and TNF-α in the spleen at weaning. Moreover, B79 and 2′-FL supplementation persistently improved crypt depth, propionic acid synthesis, and IgG and secretory IgA production, as well as revived the gut microbiota structure and composition in adulthood. Overall, our study suggests that early-life supplementation with B79 alone or in combination with 2′-FL can mitigate ceftriaxone-induced negative effects on the gut microbiota and intestinal and immune development of mice, and these improvements can partially last into adulthood.

Abstract Glucose deprivation, a hallmark of the tumor microenvironment, compels tumor cells to seek alternative energy sources for survival and growth. Here, we show that glucose deprivation upregulates the expression of mitochondrial-cytochrome c oxidase II (MT-CO2), a subunit essential for the respiratory chain complex IV, in facilitating glutaminolysis and sustaining tumor cell survival. Mechanistically, glucose deprivation activates Ras signaling to enhance MT-CO2 transcription and inhibits IGF2BP3, an RNA-binding protein, to stabilize MT-CO2 mRNA. Elevated MT-CO2 increases flavin adenosine dinucleotide (FAD) levels in activating lysine-specific demethylase 1 (LSD1) to epigenetically upregulate JUN transcription, consequently promoting glutaminase-1 (GLS1) and glutaminolysis for tumor cell survival. Furthermore, MT-CO2 is indispensable for oncogenic Ras-induced glutaminolysis and tumor growth, and elevated expression of MT-CO2 is associated with poor prognosis in lung cancer patients. Together, these findings reveal a role for MT-CO2 in adapting to metabolic stress and highlight MT-CO2 as a putative therapeutic target for Ras-driven cancers.

Background: Hepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality. Methods: A community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants’ serum samples. The cohort data were linked to Taiwan’s National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases. Results: In 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose-response relationship of HCV viral load was further demonstrated for the mediation effect. Conclusion: Both intrahepatic and extrahepatic manifestations mediated approximately half of HCV-induced mortality. The mediation mechanisms are supported by a dose-response relationship of HCV viral load.

Abstract Recovery from spinal cord injury (SCI) is often impeded by neuroinflammation, scar formation, and limited axonal regeneration. To tackle these issues, we developed an innovative biomimetic drug delivery system using liquid nitrogen-treated M2 macrophages (LNT M2) which internalized paclitaxel (PTX) nanoparticles beforehand. These were incorporated into a gelatin methacryloyl (GelMA) scaffold, creating a multifunctional, injectable treatment for single-dose administration. The LNT M2 inherited the inflammatory factor/chemokine receptors from the living M2 macrophages and thus possessing significant inflammatory neutralizing effect. In addition, the scaffold provides slow, sustained release of PTX, promoting axonal regeneration and suppressing scar formation in SCI rats. The LNT M2-based dual-functional scaffold significantly enhances motor function, reduces neuroinflammation, and accelerates axonal regeneration by modulating the inflammatory microenvironment and preventing the formation of glial and fibrotic scars. This approach combines the regenerative effects of low-dose PTX with the immunoregulatory properties of LNT M2, leading to remarkable neurological recovery in SCI rats. Moreover, the scaffold’s straightforward preparation, ease of standardization, and “ready-to-use” nature make it a promising candidate for acute SCI intervention and future clinical applications. Graphical Abstract

Abstract Introduction Chronic alcohol consumption and tobacco usage are major risk factors for esophageal squamous cell carcinoma (ESCC). Excessive tobacco and alcohol consumption lead to oxidative stress and the generation of reactive carbonyl species (RCS) which induce DNA damage and cell apoptosis. This phenomenon contributes to cell damage and carcinogenesis in various organs including ESCC. However, it also raises an important question on how ESCC cells evade RCS-induced apoptosis and grow rapidly under these conditions. Therefore, we hypothesize that some enzymes produced by ESCC cells are capable of catabolizing RCS, preventing ESCC neoplastic cells from undergoing RCS-induced apoptosis, potentially contributing to ESCC progression. Methods To identify significant gene clusters involved in the metabolism of RCS in ESCC, we used an Agilent SurePrint G3 Human V2 GE 8 × 60 K microarray kit to analyze differentially expressed genes between nine paired ESCC tissues and adjacent normal esophageal tissues taken from areas distant from the tumor site. Bioinformatics analysis using gene ontology (GO) was performed to categorize these genes. To validate the findings, immunohistochemical staining in specimens from 169 surgically resected ESCC patients was performed and then correlated with treatment outcomes. Furthermore, the identified signaling pathway and its biological effects were investigated in ESCC cell lines in vitro and 4-nitroquinoline 1-oxide (4-NQO)-induced-ESCC murine model in vivo. Results Interestingly, we found that one of the significantly altered 57 GO molecular function domain terms (GO:0004033 aldo-keto reductase activity; P = 0.021) between nine paired ESCC tumors and adjacent normal tissue specimens was associated with the RCS metabolism. Among significant genes within this domain, AKR1B10 (aldo-keto reductase family 1 member B10; P = 0.006) was identified as the most significantly altered gene. Immunohistochemical analysis revealed that AKR1B10 expression was higher in ESCC cells than in adjacent normal esophageal epithelium. In addition, AKR1B10 expression was independently significantly associated with a poorer prognosis in 169 ESCC patients. Enzyme-linked immunosorbent assay results further demonstrated that blood AKR1B10 concentrations were significantly higher in 72 ESCC patients than in 24 healthy controls. In vitro experiments revealed that inhibiting endogenous AKR1B10 enhanced the cytotoxicity of 4-hydroxy trans-2-nonenal, a type of RCS. In a 4-NQO-induced-ESCC murine model, oleanolic acid, an AKR1B10 inhibitor, significantly reduced the incidence of esophageal tumors. Conclusions Our findings suggested that AKR1B10 is an independent adverse prognosticator for patients with ESCC, and could prevent ESCC neoplastic cells from undergoing RCS-induced apoptosis, and promote ESCC progression. Therefore, AKR1B10 signaling could be a potential therapeutic strategy for ESCC.

Endothelial–mesenchymal transition (EnMT) is the transversion of endothelial cells to mesenchymal cells under certain physiological or pathological conditions. When EnMT occurs in the corneal endothelium, corneal endothelial cells (CECs) lose their normal function and thus cannot maintain corneal clarity. Studies have shown that the mechanism of EnMT in CECs involves the transforming growth factor-β (TGF-β) signaling pathway, and one of the important inhibitors of the TGF-β/Smad2/3 pathway is sirtuin-1 (SIRT1). In this study, we used a rat model of corneal endothelium injury and TGF-β1-treated human CECs to induce EnMT, aiming to explore whether SIRT1 activation inhibits corneal EnMT in vivo and in vitro. SIRT1 was activated and suppressed using resveratrol (RSV) and EX527, respectively. The endothelial markers and mesenchymal markers were measured by immunofluorescence and Western blot assays. Co-immunoprecipitation was used to detect the interaction between SIRT1 and Smad2/3. The results showed that after mechanical injury, the group treated with RSV-activated SIRT1 regained corneal transparency and recovered from edema faster than the control group. Moreover, RSV-activated SIRT1 downregulated the expression levels of alpha smooth muscle actin (α-SMA), vimentin, and Snail and upregulated the expression levels of E-cadherin and Na+/K+-ATPase both in vivo and in vitro, but these effects were reversed when SIRT1 was inhibited by EX527. SIRT1 also upregulated the expression levels of TGF-β receptor 1 and phosphorylated Smad2/3. The interaction between SIRT1 and Smad2/3 in vitro was confirmed by co-immunoprecipitation. Overall, our results indicate that SIRT1 activation inhibits corneal EnMT via the TGF-β/Smad2/3 pathway, which may be a potential therapeutic target for corneal endothelium dysfunction.

Abstract Background Cadmium is a ubiquitous toxic metal and environmental pollutant. More and more studies have shown that cadmium exposure can damage lung function. Alveolar epithelial cells (AECs) are structural cells that maintain the stability of lung function. The injury of AECs is an essential determinant of many lung diseases. In the lung, cadmium accumulation can cause damage to AECs. However, the specific mechanism is still unclear. This study aimed to explore the key mechanism underlying the injury of AECs caused by cadmium exposure. Methods The main modes of death of AECs induced by cadmium exposure were evaluated in vivo and in vitro. Transcriptomic changes of AECs induced by cadmium exposure were analyzed using RNA-sequence. Mitochondrial ROS scavengers (mitoQ), voltage-dependent anion channel 1 (VDAC1) oligomer inhibitor (VBIT4), and cyclic GMP-AMP synthase (cGAS) inhibitor (RU.521) were used to assess whether cadmium exposure triggered pyroptosis of AECs by inducing mitochondrial stress to activate the cGAS-STING-NLRP3 axis. Results In this study, the expression of pyroptosis-related proteins was significantly up-regulated in the cadmium-exposed AECs, while the expression of apoptosis, necroptosis, and ferroptosis-related proteins had no significant up-regulated. The pan-caspase inhibitor ZVAD-FMK significantly reduced cell death. Thus, our research indicates that pyroptosis is the primary type of AEC death exported to cadmium. Mechanistically, RNA-seq and Western Blot results showed that cadmium exposure activated the cGAS-STING pathway in AECs and promoted pyroptosis by activating the NLRP3 inflammasome. Further investigation of the mechanism found that cadmium exposure caused mitochondrial oxidative stress, which led to mtDNA leakage into the cytoplasm and activated the cGAS-STING pathway. In addition, inhibition of the cGAS-STING pathway significantly alleviated lung injury induced by cadmium exposure in mice. Conclusion Our study confirmed that pyroptosis of AECs was a vital mechanism of lung injury after cadmium exposure in a cGAS-STING-dependent manner, which may provide a new target for the treatment of lung diseases induced by cadmium exposure.

Abstract This study elucidates the in vivo genetic mechanisms contributing to the emerging resistance to carbapenem in Shewanella algae through a lens of adaptive microbial evolution. Leveraging PacBio amplification-free sequencing, we tracked the evolution of β-lactam resistance in clinical isolates from a persistent S. algae bacteremia case amidst antimicrobial therapy. Our investigation spotlighted a recurrent G547W mutation in the sensor histidine kinase (pdsS), which was associated with the overexpression of an OmpA-like protein (pdsO) within a proteobacteria-specific sortase system. Intriguingly, we observed a recurrent switch between wild-type and G547W alleles, revealing an adaptive expansion and contraction of underlying cell subpopulations in response to β-lactam exposure. Comparative transcriptome analyses further demonstrated the overexpression of genes pivotal for membrane integrity, biofilm formation, immune evasion, and β-lactamase activation in resistant samples. This underscores the pre-existence of resistant cells at minuscule frequencies even without antibiotic pressure, potentially explaining the within-host emergence of resistance during antibiotic treatments. Our findings provide pivotal insights into the dynamic genetic adaptations of S. algae under therapeutic pressures, unmasking intricate resistance mechanisms and highlighting the critical role of subpopulation dynamics in treatment outcomes.

Abstract Charge density wave (CDW) is the phenomenon of a material that undergoes a spontaneous lattice distortion and modulation of the electron density. Typically, the formation of CDW is attributed to Fermi surface nesting or electron-phonon coupling, where the CDW vector (Q CDW) corresponds to localized extreme points of electronic susceptibility or imaginary phonon frequencies. Here, we propose a new family of multiple CDW orders, including chiral Star-of-David configuration in nine 2D III2–VI3 van der Waals materials, backed by first-principles calculations. The distinct feature of this system is the presence of large and flat imaginary frequencies in the optical phonon branch across the Brillouin zone, which facilitates the formation of the diverse CDW phases. The electronic structures of 2D III2–VI3 materials are relatively simple, with only III-s,p and VI-p orbitals contributing to the formation of the CDW order. Despite that, the CDW transitions involve both metal-to-insulator and insulator-to-insulator transitions, accompanied by a significant increase in the bandgap caused by an enhanced electronic localization. Our study not only reveals a new dimension in the family of 2D CDWs, but is also expected to offer deeper insights into the origins of the CDWs.

Abstract To promote the energy accommodation of both electrical and heating power while considering the source–load uncertainties, a peer‐to‐peer (P2P) energy trading model among prosumers in the integrated electric–thermal system is proposed here, considering the energy trading agent (ETA) with self‐build energy system. The solar heat‐pump hybrid thermal water system (SPTS) and the transferring loss of heating power is considered and modelled based on the principle of steady‐state thermal transfer. Since the variations of load and PV cannot be described by any single common distribution, the chance‐constraints programming based on the Gaussian mixture model (GMM) is proposed to handle the uncertainty of the net load. As the proposed power trading problem is a non‐convex problem with binary variables, an improved alternating direction method of multiplier (ADMM) based on the predictor‐corrector and two‐stage cycle iterations is proposed to enhance the convergence performance of standard ADMM. Finally, an example simulation verifies the effectiveness; this results show that the proposed model can decrease the total cost by 26.7% and enhance local energy balance by 61.8% compared to other cases.

AIM: To investigate the efficacy and mechanisms of indirect intense pulsed light (IPL) irradiation on meibomian gland dysfunction (MGD). METHODS: A total of 60 MGD patients was included in this prospective randomized controlled trial. Patients were randomly assigned 1:1 into two groups (3-mm group and 10-mm group) in which IPL was applied at distances from the lower eyelid margin of 3 and 10 mm, respectively. Both groups received three times treatment with 3-week interval. Meibomian gland yield secretion score (MGYSS), standard patient evaluation of eye dryness (SPEED) questionnaire, tear break-up time (TBUT), corneal fluorescein staining (CFS), and in vivo confocal microscopy were performed at baseline and after every treatment. RESULTS: After three IPL treatments, both groups had significant improvement in MGYSS (both P

Abstract Background Isocitrate dehydrogenase (IDH) inhibitors have shown great promise in the treatment of cancers with IDH mutations. There have been numerous clinical trials conducted on IDH inhibitors, and to evaluate their efficacy and safety, we aim to perform a meta-analysis. Methods To gather data on the efficacy and safety of IDH inhibitors for IDH-mutated cancers, we systematically searched through databases including PubMed, EMBASE, and Cochrane Library. Using RevMan5.4, we performed a meta-analysis and calculated the odds ratio (OR) or weighted mean difference (WMD) with a 95% confidence interval (95%CI). The parameters considered were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs), and TRAEs ≥ 3. Results This meta-analysis included four studies, involving a total of 751 patients. According to the analysis, there was no significant difference in overall survival, treatment-related adverse events, and severe treatment-related adverse events between the experimental group (receiving IDH inhibitors) and the control group. However, the progression-free survival, objective response rate, and disease control rate in the experimental group were significantly higher than those in the control group. Conclusion The overall efficacy of IDH inhibitors in treating cancers with IDH mutations is superior to that of conventional medical therapy, potentially providing more clinical benefits to patients. The incidence of adverse events was not significantly different from conventional medical therapy. Therefore, IDH inhibitors should be considered as the preferred choice for treating cancers with IDH mutations. However, further randomized controlled clinical trials are still required for verification.

For improving the actuation performance at low electric fields of dielectric elastomers, achieving high dielectric constant (ɛr) and low modulus (Y) simultaneously has been targeted in the past decades, but there are few ways to accomplish both. In contrast to the classical strategies such as incorporating plasticizers or ceramic to prepare the silicon-based dielectric elastomers, here, blending an amino-complexed hybrid (polyethyleneimine (PEI)-Ag) with polydimethylsiloxane (PDMS) elastomer is reported as an alternative strategy to tailor the ɛr and Y. PEI-Ag not only exhibits excellent dielectric enhancement properties but also minimizes the PDMS crosslinking through amino-complexed reaction between PEI and Pt catalysts. The prepared dielectric elastomers have a ɛr of 7.2 @ 103 ​Hz and Y of 1.14 ​MPa, leading to an actuation strain of 22.27 ​% at 35 ​V/μm. Hence, incorporating such novel hybrids based on dual amino-complexed effect on both matrix and particles sufficiently promotes the actuated performance of dielectric elastomers.

Abstract Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice. These mice significantly mitigate diet-induced obesity, echoing AA005’s anti-obesity effects. AA005 treatment and Hadha deletion in adipose tissues increase body temperature and energy expenditure in high-fat diet-fed mice. The beneficial impact of AA005 on obesity mitigation is ineffective without uncoupling protein 1 (UCP1), essential for thermogenesis regulation. Our investigation shows the interaction between AA005 and HADHA in mitochondria, activating the UCP1-mediated thermogenic pathway. This substantiates AA005 as a promising compound for obesity treatment, targeting HADHA specifically.

Abstract Background Previous studies have shown that the Gaming Disorder Test (GDT) and Gaming Disorder Scale for Adolescents (GADIS-A) have promising validity and reliability when assessing symptoms of gaming disorder among young adults. However, validity and reliability properties of the two scales have not been established among a Vietnamese population. Objective The present study translated the GDT and GADIS-A into Vietnamese and examined their factor structures, measurement invariance, convergent validity, concurrent validity, and divergent validity among university students. Methods A total of 610 young adults (mean age = 21.09 years; 63.4% females) were recruited using convenience sampling and who completed a paper-and-pencil survey between April and June 2023. All participants completed a demographic questionnaire, GDT, GADIS-A, and six standardized scales related to gaming disorder, social media addiction, smartphone addiction, and psychological distress. Confirmatory factor analysis (CFA), internal consistency testing, and Pearson’s correlations were performed. Results CFA showed that the GDT had a one-factor structure and the GADIS-A had a two-factor structure. The internal consistency was excellent for both scales among this population. Moreover, both GDT and GADIS-A showed convergent, concurrent, and divergent validity with other standardized scales. Conclusion The Vietnamese versions of the GDT and GADIS-A have good psychometrics, which may be utilized in future research regarding gaming disorder among Vietnamese populations.

A delayed diffusive predator-prey system with nonmonotonic functional response subject to Neumann boundary conditions is introduced in this paper. First, we analyze the associated characteristic equation to research the conditions for local stability of the positive equilibrium point and the occurrence of Turing instability induced by diffusion in the absence of delay. Second, we provide conditions for the existence of Hopf bifurcation driven by time delay. By utilizing the normal theory and center manifold theorem, we derive explicit formulas for Hopf bifurcation properties such as direction and stability from the positive equilibrium. Third, a hybrid controller is added to the system. By judiciously adjusting the control parameters, we effectively enhance the stability domain of the system, resulting in a modification of the position of the Hopf bifurcation periodic solutions. Numerical simulations demonstrate the presence of rich dynamical phenomena within the system. Moreover, sensitivity analysis was conducted using Latin hypercube sampling (LHS)/partial rank correlation coefficient (PRCC) to explore the impact of parameter variations on the output of prey and predator populations.

China is one of the countries in the world with the most frequent occurrence of continental earthquakes and the greatest impacts of earthquake disasters. In particular, the Qinghai-Tibet Plateau is a region characterized by a wide spatial distribution of continental earthquakes, shallow epicenters, complex seismic origins, and significant disaster losses, making it highly susceptible to seismic events. The need for seismic geological survey is becoming increasingly urgent in this area. Based on regional geological eological data，high-precision satellite remote sensing images and DEM elevation data，this paper interprets the active faults in the region of Xigaze. The results show that the active faults in the Xigaze area are mainly concentrated in the rift valleys and their periphery, with tectonic activity varying spatially. The tectonic activity of active faults in the eastern rift is stronger than that in the western rifts. Additionally，the tectonic activity of active faults in each rift also shows a clear segmentation feature. At the same time, this paper comprehensively considers the characteristics of active faults, topography and geomorphology and stratigraphic lithology in the Xigaze area. It preliminarily evaluates the potential risk of earthquake disasters in 204 towns under its jurisdiction. The results show that there are 57 towns with “extremely high risk” “high risk” and “high-medium risk” of earthquake disasters, accounting for about 28% of the total number of towns in the region.

Abstract Symmetry plays an important role in determining the physical properties in condensed matter physics, as the symmetry operations of any physical property must include the symmetry operations of the point group of the crystal. As a consequence, crystallographic polarity and chirality are expected to have an impact on the Cooper pairing in a superconductor. While superconductivity with crystallographic polarity and chirality have both been found in a few crystalline phases separately; however, their coexistence and material realizations have not been studied. Here, by utilizing transport, Raman scattering, and transmission electron microscopy, we unveil a unique realization of superconductivity in single-crystalline Mo3Al2C (superconducting T c=8 K) with a polar charge-density-wave phase and well-defined crystallographic chirality. We show that the intriguing charge density wave order leads to a noncentrosymmetric-nonpolar to polar transition below T*=155K via breaking both the translational and rotational symmetries. Superconductivity emerges in this polar and chiral crystal structure below T c=8 K. Our results establish that Mo3Al2C is a superconductor with crystallographic polarity and chirality simultaneously, and motivate future studies of unconventional superconductivity in this category.

Abstract Objectives The pathogen of Pantoea stewartii (Ps) is the causal agent of bacterial disease in corn and various graminaceous plants. Ps has two subspecies, Pantoea stewartii subsp. stewartia (Pss) and Pantoea stewartii subsp. indologenes (Psi). This study presents two complete genomes of Ps strains including ATCC 8199 isolated from maize and PSCN1 causing bacterial wilt in sugarcane. The two bacterial genomes information will be helpful for taxonomy analysis in this genus Pantoea at whole-genome levels and accurately discriminated the two subspecies of Pss and Psi. Data description The reference strain ATCC 8199 isolated from maize was purchased from Beijing Biobw Biotechnology Co., Ltd. (China) and the strain of PSCN1 was isolated from sugarcane cultivar YZ08-1095 in Zhanjiang, Guangdong province of China. Two complete genomes were sequenced using Illumina Hiseq (second-generation) and Oxford Nanopore (third-generation) platforms. The genome of the strain ATCC 8199 comprised of 4.78 Mb with an average GC content of 54.03%, along with five plasmids, encoding a total of 4,846 gene with an average gene length of 827 bp. The genome of PSCN1 comprised of 5.03 Mb with an average GC content of 53.78%, along with two plasmids, encoding a total of 4,725 gene with an average gene length of 913 bp. The bacterial pan-genome analysis highlighted the strain ATCC 8199 was clustered into a subgroup with a Pss strain CCUG 26,359 from USA, while the strain PSCN1 was clustered into another subgroup with a Ps strain NRRLB-133 from USA. These findings will serve as a useful resource for further analyses of the evolution of Ps strains and corresponding disease epidemiology worldwide.

Abstract Introduction Ciprofol is a novel propofol analogue with a characteristic of hemodynamic stability. At present, there is a lack of research comparing the hemodynamic stability of ciprofol and propofol during painless colonoscopy. In this study, we aim to test the hypothesis that ciprofol is superior to propofol in terms of hemodynamic stability for sedation anesthesia in patients undergoing colonoscopy. Methods A total of 222 patients were randomized into two groups. Patients in group P (n = 112) and group C (n = 110) received propofol and ciprofol sedation, respectively. Noninvasive blood pressure were monitored starting from induction (T 0) to the end of the procedure, at 2-min intervals (T 1 to T 10). Heart rate variability (HRV), pain injection, Modified Observer's Assessment of Alertness and Sedation (MOAA/S) score, body movement, doses of norepinephrine, modified Aldrete score, drug-related adverse reactions, and patient satisfaction and endoscopist satisfaction were recorded. Results In group C, fewer patients experienced a decrease in blood pressure with a higher HRV after induction sedation, the incidence of pain injection was reduced, the amount of norepinephrine dose was decreased, patient satisfaction was increased compared with group P (all P

Abstract Immune-cell reprogramming driven by mitochondria-derived reactive electrophilic immunometabolites (mt-REMs—e.g., fumarate, itaconate) is an emerging phenomenon of major biomedical importance. Despite their localized production, mt-REMs elicit significantly large local and global footprints within and across cells, through mechanisms involving electrophile signaling. Burgeoning efforts are being put into profiling mt-REMs’ potential protein-targets and phenotypic mapping of their multifaceted inflammatory behaviors. Yet, precision indexing of mt-REMs’ first-responders with spatiotemporal intelligence and locale-specific function assignments remain elusive. Highlighting the latest advances and overarching challenges, this perspective aims to stimulate thoughts and spur interdisciplinary innovations to address these unmet chemical-biotechnological needs at therapeutic immuno-signaling frontiers.

Abstract To investgate the effects of potassium (K) application on the agronomic traits and fruit quality of Lycium barbarum L. (Goji), three levels of K fertilizer, namely LK (25 g/plant), CK (50 g/plant), and HK (75 g/plant), were applied to plants in phytotron for observing and measuring relevant indicators. The investigation involved seven agronomic traits: plant height, plant stem diameter, new branch increment, yield of fresh fruits per plant, dry fruit quantity within 50 g, ratio of different grade fruits, and ratio of longitudinal diameter to transverse diameter of Goji fruits. The results showed that K application level had significant effect on ratio of the longitudinal diameter to the transverse diameter of fresh Goji fruits, and that the influence on other agronomic traits was slight. In the meanwhile, the concentrations of amino acids, betaine, polysaccharides and flavonoids of Goji fruits in different levels of K fertilizer were tested. The K treatment increased the content of glutamic acid, and decreased that of flavonoids (P

Abstract Background Recent randomized phase III trials have demonstrated the efficacy of anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in treating patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). However, a large proportion of such patients still have poor response. This study aimed to identify biomarkers for predicting anti-PD-1 ICI treatment outcomes . Methods We retrospectively analyzed 144 patients with RMHNSCC who received anti-PD-1 ICIs after progression to platinum-based chemotherapy between January 2017 and December 2022 at Kaohsiung Chang Gung Memorial Hospital. Data on clinicopathological parameters, albumin levels, calcium levels, and other pretreatment peripheral blood biomarkers, including total lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI) were collected and correlated with the treatment outcome of anti-PD-1 ICIs. Results Low tumor proportion score (TPS), low combined positive score (CPS), NLR ≥ 5, PLR ≥ 300, hypercalcemia, hypoalbuminemia, and PNI

OBJECTIVES: Laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC) has been well known for its advantages in the past 10 years, but little is known regarding its oncologic outcomes while the technique is being developed at an institution. This study aimed to evaluate the safety and effectiveness of LH for patients with primary HCC at favorable locations, focusing on postoperative short- and long-term outcomes during the development period. MATERIALS AND METHODS: We retrospectively reviewed patients diagnosed with primary HCC who underwent hepatectomy between January 2013 and December 2019 at Hualien Tzu Chi Hospital. Patients with HCC at favorable locations (anterolateral segments) were collected and divided into laparoscopic and open hepatectomy (OH) groups. The data for long-term outcomes, as the primary endpoint, and postoperative outcomes, as the secondary endpoint, were collected. Results: The review included 159 patients, among which 42 and 44 patients in favorable locations underwent open and laparoscopic hepatectomies, respectively. There were no significant differences in intraoperative blood loss, major complication rate, and 90-day mortality rate between the two groups. The laparoscopic group had a lower transfusion rate, shorter postoperative hospital stay, and lower 90-day readmission rate. There were no significant differences in 12-, 36-, and 60-month overall survival and disease-free survival. Conclusion: LH for favorably located HCC is the preferred surgical approach compared to OH due to the decreased transfusion rate, shorter postoperative hospital stay, and lower 90-day readmission rate. LH did not compromise the 90-day mortality rate with sustained long-term overall and disease-free survival. LH for favorably located HCC is a safe and effective surgical approach even during the development period.

Numerous studies conducted in recent years indicate that mammalian E3 ubiquitin ligases serve as key regulators in the maintenance of cellular homeostasis by targeting the ubiquitination of substrate proteins and activating downstream signaling pathways. SYVN1, an E3 ubiquitin ligase, is characterized by its significant functions in regulating various biological processes, including molecular mechanisms related to gene expression, signaling pathways, and cell death, among others. Consequently, SYVN1 plays a crucial role in both normal human physiology and the pathogenesis of various diseases, such as oncogenesis, cardiovascular disorders, immune regulation, skeletal anomalies, and neurological diseases. This review synthesizes recent findings regarding the physiological and pathophysiological roles of SYVN1, offering new insights into potential strategies for the prevention and treatment of human diseases, as well as suggesting avenues for future drug development. In this Review, we summarize the latest findings regarding the physiological and pathophysiological roles of SYVN1, elucidating the mechanisms by which SYVN1 can regulate the progression of various diseases in humans. These important findings provide new avenues for further investigation of SYVN1 protein, new insights into potential strategies to prevent and treat human diseases, and new directions for future drug development.

Antibacterial hydrogels are promising for combating infections and promoting wound healing. Nevertheless, excessive antibiotics induce resistance, and high metal ion levels cause cytotoxicity, complicating healing. Here, we introduce a hydrogel incorporating polydopamine-coated bioactive glass (BGs@PDA) on reduced graphene oxide (rGO) with photothermal therapy (PTT) and silver nanoclusters (AgNCs) for synergistic antibacterial treatment. This design enables rapid bacterial eradication and controlled release. Near-infrared-assisted heating provides noninvasive, targeted hyperthermia, killing bacteria quickly. Post-PTT addition of low-dose AgNCs reduces toxicity while enhancing antimicrobial efficacy and biocompatibility. BGs@PDA-loaded rGO prevents sedimentation, improves photothermal conversion and conductivity, and stabilizes the hydrogel structure. Constructed from chitosan and hydroxyethyl cellulose, the hydrogel is cross-linked by PDA and rGO, enhancing mechanical strength, adhesion, self-healing, free radical scavenging, and continuous wound exudate absorption. PDA encapsulation facilitates BGs degradation, improving the wound microenvironment. In vivo studies confirm accelerated healing and potent synergistic antibacterial effects, indicating its potential as a low-dose, antibiotic-free alternative for clinical wound infection management.

ABSTRACT Klebsiella pneumoniae is a prominent Gram-negative and encapsulated opportunistic pathogen that causes a multitude of infections such as severe respiratory and healthcare-associated infections. Despite the widespread anti-microbial resistance and the high mortality rate, currently, no clinically vaccine is approved for battling K. pneumoniae. To date, messenger RNA (mRNA) vaccine is one of the most advancing technologies and are extensively investigated for viral infection, while infrequently applied for prevention of bacterial infections. In the present study, we aim to construct a new mRNA vaccine encoding YidR or combining with a tissue plasminogen activator signal sequence for preventing K. pneumoniae infection. Adaptive immunity was determined in mRNA vaccines-immunized mice and the protective effects of mRNA vaccines were evaluated in K. pneumoniae infected models. The results showed that lipid nanoparticle (LNP)-YidR-mRNA vaccine was produced with good morphology, high the encapsulation efficiency, and the specific antigen was highly expressed in cells in vitro. In addition, immunization with either LNP-YidR or LNP-YidR-SP elicited a Th1-biased immune response, reduced bacterial load, and provided broad protection in the lung infection models. Importantly, the LNP-YidR-SP mRNA vaccine induced strong adaptive humoral and cellular immunity and increased the survivability of mice compared to the other groups. Our findings serve as a focal point for developing a potential mRNA vaccine against K. pneumoniae, indicating the potential of mRNA vaccines for improving next-generation bacterial vaccine.IMPORTANCEK. pneumoniae is a notorious and clinical bacterium that is evolving in community-acquired and nosocomial settings. This opportunistic pathogen causes severe infectious diseases, including urinary tract infection and pneumonia, and causes a concerning global public burden. Despite efforts having been created to develop different types of K. pneumoniae vaccines, there is no licensed vaccine for preventing K. pneumoniae infection. Therefore, to develop an effective tactic is essential to combat K. pneumoniae-caused diseases. This study provides a novel vaccine strategy against K. pneumoniae and a potent platform to elicit high levels of humoral and cell-meditated immunity.

Current treatments for chronic obstructive pulmonary disease (COPD), a common respiratory condition, include oxygen therapy and steroids for temporary relief. In this study, we established a rat model of cigarette smoke (CS)–induced COPD and investigated the benefits of a hydrogen–oxygen generator in this model. CS–exposed rats were treated using either a hydrogen–oxygen generator or a steroid. A hydrogen–oxygen generator reduced the neutrophil, lymphocyte, and eosinophil counts compared to natural recovery, whereas steroid treatment increased the total white blood cell, neutrophil, lymphocyte, monocyte and eosinophil counts. Furthermore, the mean linear intercept and the mean alveolar number were 59.8%, and 188.3%, respectively, after treatment with the generator, compared to the values observed with natural recovery. Finally, the generator increased the tricuspid annular plane systolic excursion values by 113.1% compared with the values in natural recovery. Our findings indicate successful establishment of a rat model of CS–induced COPD and demonstrate the potential benefits of using a hydrogen–oxygen generator for COPD patients.

BackgroundDysbiosis of the lung microbiome can contribute to the initiation and progression of lung cancer. Synchronous multiple primary lung cancer (sMPLC) is an increasingly recognized subtype of lung cancer characterized by high morbidity, difficulties in early detection, poor prognosis, and substantial clinical challenges. However, the relationship between sMPLC pathogenesis and changes in the lung microbiome remains unclear.MethodsIn this study, 16S rRNA sequencing was performed on clinical samples to analyze lung microbiome composition. Real-time quantitative PCR (qPCR) was used to quantify bacterial abundance in lung tissues. In addition, flow cytometry was conducted to evaluate cell cycle progression and apoptosis in lung tumor cells.ResultsClinical cohort studies demonstrated that sMPLC occurrence is associated with disturbances in the lung microbiome. Notably, Streptococcus intermedius was enriched in the lungs of sMPLC patients compared with non-tumor controls and accumulated preferentially in tumor tissues. S. intermedius shortened the cell cycle and inhibited apoptosis in lung cancer cells. Analyses of oral and gut microbiomes in different patient cohorts revealed a strong correlation between oral microbiome imbalances and lung microbiome composition in sMPLC patients.ConclusionsThese findings characterize the lung microbiota in sMPLC and identify S. intermedius as a potentially influential bacterial strain. This study provides significant new insights into the diagnosis and treatment of sMPLC.

The large and rapid increase in the incidence and mortality of colorectal cancer (CRC) demonstrates the urgent need for new drugs with higher efficacy to treat CRC. However, the lack of applicable and reliable preclinical models significantly hinders the progress of drug development. Patient-derived xenograft (PDX) models are currently considered reliable in vivo preclinical models for predicting drug efficacy in cancer patients. This study successfully uses the CRC PDX model to develop clinical indications for the new multi-target kinase inhibitor BPR1J481 and demonstrated the anti-cancer mechanism and competitive advantages of this drug candidate. The results demonstrate that BPR1J481 exhibits significant anticancer efficacy by inducing apoptosis in CRC PDX tumor tissues and corresponding PDX-derived CRC cells. Through kinase competitive binding and kinase activity assays, we discover that BPR1J481 effectively inhibits SRC kinase activity by directly binding to its active site. The reduction in SRC phosphorylation observed in CRC PDX tumor tissues and derived cells upon treatment with BPR1J481 further validates its inhibitory potential. Furthermore, the decrease in viable cells after SRC knockout and the poorer prognosis observed in patients with higher SRC expression, emphasizes the critical significance and clinical relevance of SRC in CRC. Additionally, BPR1J481 exhibits robust anti-angiogenic effects by suppressing VEGF- and PDGF-induced endothelial cell proliferation, migration, and capillary-like tube formation through inhibition of VEGFR2 and PDGFRβ phosphorylation. Remarkably, BPR1J481 appears to demonstrate greater efficacy against CRC compared to regorafenib. These findings highlight the therapeutic potential of BPR1J481 for patients with CRC.

BackgroundThe nod-like receptor family pyrin domain-containing 3 (NLRP3) has been implicated in various skin diseases. However, its role in mediating 2, 4-dinitrofluorobenzene (DNFB)-induced chronic itch remains unclear.MethodsWidetype (WT) and Nlrp3 deletion (Nlrp3-/-)mice, the expression of transient receptor potential (TRP) ankyrin 1 (TRPA1) inhibitor or recombinant mice interleukin-18 (IL-18) were used to establish and evaluate the severity of DNFB-mediated chronic itch. Quantitative real-time PCR, western blotting, immunohistochemistry staining, immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA) was used to examine the expression of NLRP3 inflammasome, type 2 immunity and receptors in dorsal root ganglion (DRG) neurons related with chronic itch. Flow cytometry was performed to quantify the frequency of type 2 immune cells.ResultsThis study revealed that the NLRP3 inflammasome was activated in the skin of DNFB-induced chronic itch mice. Surprisingly, the absence of Nlrp3 exacerbated itch behavior. In Nlrp3-/- mice, IL-18 expression was downregulated, whereas markers of type 2 immunity, such as IL-4 and thymic stromal lymphopoietin (TSLP), were significantly upregulated in the skin. Furthermore, TRPA1 and its colocalization with the IL-4 receptor were increased in the DRG. Inhibition of TRPA1 or administration of recombinant IL-18 significantly reduced DNFB-induced itch behavior in Nlrp3-/- mice. Recombinant IL-18 also decreased the expression of TRPA1, IL-4, and TSLP.DiscussionThese findings suggested that the absence of Nlrp3 aggravated DNFB-induced chronic itch by exacerbating type 2 immunity in the skin and enhancing the IL-4/TSLP-TRPA1 axis, potentially driven by reduced IL-18 levels.

This observational study investigated the transfer of maternal gut microbiota to the infant gut through breast milk and its implications for infant gut health. Fecal and breast milk samples were collected from 23 healthy mother-infant pairs, with 11 breast milk samples testing positive for microbial presence. Microbial source tracking revealed that 22.89 % of breast milk microbiota originated from the maternal gut, and 25.64 % of the infant gut microbiota was derived from breast milk. Shared OTUs between the paired maternal gut, breast milk, and infant gut had a median of 109 (range: 61–148). Genera such as Bifidobacterium, Escherichia-Shigella, and Bacteroides were common across the three sites. Comparisons with the sterile milk group (n = 12) indicated a potential role for breast milk microbiota in maternal-infant microbiota transmission. This study highlights breast milk as a significant medium for microbiota transfer and provides a theoretical basis for promoting infant gut health.

ABSTRACT The mechanisms behind the high inflammatory state and immunocompromise in severe sepsis remain unclear. While microbiota’s role in immune regulation is known, the impact of pulmonary microbiota on sepsis progression is not fully understood. This study aims to investigate pulmonary microbial characteristics in septic patients and their relationship with host immune-related genes and clinical features. Fifty-four sepsis patients were divided into the immunocompromised host (ICH) group (n = 18) and the control group (n = 36). Bronchoalveolar lavage fluid (BALF) was analyzed using metagenomic next-generation sequencing (mNGS) to assess the pulmonary microbiome, and transcriptomic sequencing evaluated host gene expression. The pulmonary microbiota network in the ICH group showed notable alterations. Symbiotic bacteria like Streptococcus salivarius and Streptococcus oralis were key taxa in the control group. In contrast, opportunistic pathogens such as Campylobacter concisus and Prevotella melaninogenica, typically linked to infections in various body sites, dominated in the ICH group. Transcriptomic analysis revealed differential genes between the two groups. The downregulated differential genes in the ICH group were primarily enriched in pathways related to T-cell activation and the Type I interferon signaling pathway, both crucial for the immune system. Further correlation analysis identified significant associations between certain microbes and host genes, as well as clinical indicators, particularly with species like Campylobacter concisus, Streptococcus salivarius, Streptococcus oralis, and several species of Veillonella. These findings suggest that alterations in the pulmonary microbiome, especially the presence of opportunistic pathogens, may contribute to immune dysregulation in immunocompromised septic patients, warranting further research to explore causal relationships.IMPORTANCERecent research has substantiated the significant role of microbiota in immune regulation, which could influence high inflammatory state and immunocompromise in patients with severe sepsis, as well as provide new opportunities for acute lung injury induced by sepsis diagnosis and treatment. Our study identified some potential critical microbes (Campylobacter concisus and several species of Veillonella), which were correlated with immune-related genes and might be the novel target to regulate immunotherapy in sepsis.

Summary: Background: Impaired mitochondrial protein import machinery leads to phenotypically heterogeneous diseases. Here, we report a recurrent homozygous missense variant in the gene that encodes the translocase of outer mitochondrial membrane 7 (TOMM7) in nine patients with microcephaly, short stature, facial dysmorphia, atrophic macular scarring, and moyamoya disease from seven unrelated families. Methods: To prove the causality of the TOMM7 variant, mitochondrial morphology, proteomics, and respiration were investigated in CRISPR/Cas9-edited iPSCs-derived endothelial cells. Cerebrovascular defects and mitochondrial respiration were also examined in CRISPR/Cas9-edited zebrafish. Findings: iPSC-derived endothelial cells with homozygous TOMM7 p.P29L showed increased TOM7 stability, enlarged mitochondria, increased senescence, and defective tube formation. In addition, proteomic analysis revealed a reduced abundance of mitochondrial proteins involved in ATP synthesis or coordinating TCA cycle and gluconeogenesis. Moreover, mitochondrial respiration was slightly decreased while ATP production from glycolysis was significantly increased. Furthermore, deletion of tomm7 in zebrafish caused craniofacial and cerebrovascular defects that recapitulated human phenotypes. Notably, homozygous iPSCs differentially expressed genes involved in glycolysis and response to hypoxia. Finally, the metabolic imbalance was evidenced by decreased oxygen consumption, increased level of hexokinase 2, and enhanced glycolysis in endothelial cells derived from the patient's iPSCs. Interpretation: These results revealed the essential role of TOMM7 in balancing cellular sources of energy production at both proteomic and transcriptomic levels and provided the molecular mechanisms through which TOMM7 p.P29L variant leads to an autosomal recessive microcephalic osteodysplastic dwarfism with moyamoya disease. Funding: This work is supported by National Science and Technology Council grants and National Cheng Kung University Hospital.

ABSTRACTKlebsiella pneumoniae is an important gram-negative bacterium that causes severe respiratory and healthcare-associated infections. Although antibiotic therapy is applied to treat severe infections caused by K. pneumoniae, drug-resistant isolates pose a huge challenge to clinical practices owing to adverse reactions and the mismanagement of antibiotics. Several studies have attempted to develop vaccines against K. pneumoniae, but there are no licensed vaccines available for the control of K. pneumoniae infection. In the current study, we constructed a novel DNA vaccine, pVAX1-YidR, which encodes a highly conserved virulence factor YidR and a recombinant expression plasmid pVAX1-IL-17 encoding Interleukin-17 (IL-17) as a molecular adjuvant. Adaptive immune responses were assessed in immunized mice to compare the immunogenicity of the different vaccine schemes. The results showed that the targeted antigen gene was expressed in HEK293T cells using an immunofluorescence assay. Mice immunized with pVAX1-YidR elicited a high level of antibodies, induced strong cellular immune responses, and protected mice from K. pneumoniae challenge. Notably, co-immunization with pVAX1-YidR and pVAX1-IL-17 significantly augmented host adaptive immune responses and provided better protection against K. pneumoniae infections in vaccinated mice. Our study demonstrates that combined DNA vaccines and molecular adjuvants is a promising strategy to develop efficacious antibacterial vaccines against K. pneumoniae infections.

Background: Superabsorbent polymers (SAPs) have a remarkable ability to absorb significant quantities of water. However, their absorption capacity is significantly reduced when exposed to saline solutions, such as urine, due to the polyelectrolyte effect and charge screening. Methods: In this study, we demonstrate a zwitterionic superabsorbent polymer (ZSAP) with excellent salt-water absorption and retention capacities. ZSAP was synthesized by grafting a copolymer of p(sulfobetaine methacrylate-co-2-hydroxyethyl methacrylate) (p(SBMA-co-HEMA)) onto an acrylic acid (AA)-based hydrogel via free-radical polymerization. The introduction of zwitterionic SBMA significantly enhances the hydrophilicity of the polymer, particularly in a saline solution due to the anti-polyelectrolyte effect, thereby accelerating the rate of salt absorption. Additionally, the hydroxyl groups from HEMA facilitate the formation of covalent bonds with the AA network membrane through esterification, effectively mitigating polymer leaching. The hydration/dehydration behaviors of linear polymers were measured using the dynamic vapor sorption (DVS) method. Moreover, the salt-water absorption capacity, centrifuge retention capacity (CRC), and absorbency under load (AUL) of ZSAP with various SBMA moieties and copolymer dosages were comprehensively evaluated in a 0.9 wt% sodium chloride solution. Additionally, the water retention under different temperatures and polymer leaching of ZSAP were investigated. Significant Findings: The copolymer p(SBMA-co-HEMA) not only demonstrates a high salt-water absorption rate at 90% RH in a 0.9 wt% NaCl solution but also exhibits superior water retention at 0% RH compared to the AA polymer. Moreover, the ZSAP exhibits superior salt-water absorption capacity and AUL in a 0.9 wt% NaCl solution compared to conventional AA-based SAP. Additionally, the introduction of the hydroxyl moiety from the p(SBMA-co-HEMA) copolymer reduces free polymer leaching from ZSAP. This work presents an approach for the development of new SAP with high salt-water absorption and retention.

Summary: Antibody–drug conjugates (ADCs) have become an important class of anticancer drugs in solid tumors including drug-resistant gynecologic malignancies. TROP2 is a cell surface antigen that is highly expressed in ovarian carcinoma (OC) but minimally expressed in normal ovarian tissues. In this study, we aimed to identify how TROP2-specific ADC, sacituzumab govitecan (SG), modulates DNA damage response pathways in drug-resistant OC. We found that SG induces G2/M arrest, increases RPA1 foci, and decreases replication fork speed, resulting in replication stress in TROP2-positive cells while these were less evident in TROP2-negative cells. In OC in vitro and in vivo models, SN-38 sensitivity and TROP2 expression play key roles in response to either ATR inhibitor or SG alone, or in combination. Additionally, inhibition of translesion DNA synthesis enhances SG and PARP inhibitor (PARPi) sensitivity in PARPi-resistant OC cells. These findings provide mechanistic insights for clinical development of SG in drug-resistant OC.

Abstract Lead-free SrBi2Ta2O9 (SBT) has been a promising ferroelectric material for various applications such as electronics and data storage due to its outstanding ferroelectric properties including high fatigue endurance and low leakage current. However, the atomic-scale domain structure and switching dynamics of ferroelectric SBT remain elusive. This study reveals that spontaneous polarization arises from canted bismuth-cation displacements, forming 90° and Ising-type 180° domain walls. Interestingly, topological pairs of ferroelectric vortex and antivortex connect ferroelectric boundaries where three domain walls converge. In situ electrical biasing transmission electron microscopy (TEM) reveals the dominance of 180° switching over 90°, where oxygen octahedral connectivity is protected by ferroelastic energy in the 90° domain wall. Consequently, all 180° domain walls and (anti)vortices are removed, leaving only 90° domain walls in the electrically poled states. Chemical deterioration along domain walls highlights vulnerability of SBT to ferroelectric fatigue. This study provides insight into crucial aspects for practical applications of SBT.

Abstract Background There is an increasing number of human immunodeficiency virus (HIV) reported cases among students in Southwest China. However, the data on HIV/sex-related knowledge, attitude toward sex, sexual behaviors, and correlates of pre-exposure prophylaxis (PrEP)-eligible behaviors among college students in this area is still limited. This study aimed to assess the prevalence of HIV/sex-related knowledge, sexual attitudes, sexual behaviors, and factors associated with PrEP-eligible behaviors among college students. Method An online survey from 2020 to 2021 based on a multistage stratified and cluster sampling method was conducted among college students in Southwest China, and a well-designed questionnaire collected data. Propensity score matching (PSM), logistic, and log-binomial regression were used to identify the determinants of PrEP-eligible behaviors. Result A total of 108,987 students participated in the survey, and 92,946 provided valid responses. 91.6% (85,145/92,946) had good HIV-related knowledge, while only 26.0% (24,137/92,946) reported awareness of sex-related knowledge. Furthermore, more than half of the participants (64.5%) held negative stances towards engaging in “one-night stand”, and 58.9% (617/1,047) reported PrEP-eligible behaviors. Log-binomial regression analysis indicated that unaware of HIV-related knowledge (aPR = 1.66, 95% CI:1.22–2.26, P = 0.001), not discussing about sex with their parent(s) (aPR = 1.16, 95% CI:1.01–1.33, P = 0.021), not receiving sex-related education in school(aPR = 1.24, 95% CI: 1.07–1.45, P = 0.005), not participating in HIV/AIDS prevention activities in the past year (aPR = 1.32, 95%CI:1.09–1.60, P = 0.004), experiencing forced sex (aPR = 2.08, 95% CI: 1.19–3.63, P = 0.010), and having the drug abuse (aPR = 22.21, 95% CI:5.59–88.31, P

Abstract Since 2016, China has progressively relaxed family planning policies to stimulate birth rates. This paper examines the behavioral health repercussions of China’s 2016 universal two-child policy (UTCP) by analyzing sleep pattern data from China Family Panel Studies. Napping is a composite indicator that denotes health outcomes, job quality, and personal well-being. It reveals work conditions and environments to some extent. UTCP may lead to heightened social expectations regarding pregnancy likelihood, and changes in social expectations within the workplace may make work environments less equitable and more stressful for females. Leveraging a difference-in-difference model, this paper explores how napping behaviors among the working-age cohort have responded to the policy shifts. Our analysis reveals a gender discrepancy in response to the policy, specifically, females exhibit a discernible reduction in the likelihood of napping, as well as in the duration of both daytime naps and daily sleep. Conversely, such effects are not significant among males. These results suggest policy consequences extend beyond individuals directly impacted by childbirth or contemplating parenthood. Hence, while promoting fertility is still the government’s goal, policymakers are encouraged to consider the broader challenges the female population faces from social and workplace environment factors.

Abstract Background Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. Methods Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs’ gene and protein expression was conducted using human colon cancer cells. Results Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. Conclusion This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

Abstract Direct copper-to-copper (Cu-Cu) bonding is a promising technology for advanced electronic packaging. Nanocrystalline (NC) Cu receives increasing attention due to its unique ability to promote grain growth across the bonding interface. However, achieving sufficient grain growth still requires a high thermal budget. This study explores how reducing grain size and controlling impurity concentration in NC Cu leads to substantial grain growth at low temperatures. The fabricated NC Cu has a uniform nanograin size of around 50 nm and a low impurity level of 300 ppm. To prevent ungrown NC and void formation caused by impurity aggregation, we propose a double-layer (DL) structure comprising a normal coarse-grained (CG) layer underneath the NC layer. The CG layer, with a grain size of 1 μm and an impurity level of 3 ppm, acts as a sink, facilitating impurity diffusion from the NC layer to the CG layer. Thanks to sufficient grain growth throughout the entire NC layer, cross-interface Cu-Cu bonding becomes possible under a low thermal budget, either at 100 °C for 60 min or at 200 °C for only 5 min.

Abstract Background Survival analysis has been used to characterize the time-to-event data. In medical studies, a typical application is to analyze the survival time of specific cancers by using high-dimensional gene expressions. The main challenges include the involvement of non-informaive gene expressions and possibly nonlinear relationship between survival time and gene expressions. Moreover, due to possibly imprecise data collection or wrong record, measurement error might be ubiquitous in the survival time and its censoring status. Ignoring measurement error effects may incur biased estimator and wrong conclusion. Results To tackle those challenges and derive a reliable estimation with efficiently computational implementation, we develop the R package AFFECT, which is referred to Accelerated Functional Failure time model with Error-Contaminated survival Times. Conclusions This package aims to correct for measurement error effects in survival times and implements a boosting algorithm under corrected data to determine informative gene expressions as well as derive the corresponding nonlinear functions.

Abstract Background Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. Methods The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. Results The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2‐butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2‐butoxyethyl) phosphate (r = 0.88, p

This study was performed to investigate the inhibitory mechanisms of 3 plant polyphenols, grape seed extract (GSE), lotus seed proanthocyanidins (LSPC) and lotus root polyphenol extract (LRPE), against Shewanella putrefaciens. Their antibacterial effects were determined in terms of minimum inhibitory concentration (MIC) and the growth curve of S. putrefaciens. By scanning electron microscopy (SEM), relative conductivity, propyridine iodide (PI) staining, alkaline phosphatase (AKP) activity, extracellular protein content, nucleic acid leakage, Na+ K+ -ATPase activity and membrane protein fluorescence analysis, the antibacterial mechanism was explored. The results showed that the MICs of GSE, LRPE and LSPC were 31.25, 62.25 and 125.00 μg/mL, respectively. After S. putrefaciens was treated with the polyphenols, the position of membrane proteins was changed, the fluorescence intensity was reduced, the morphology was altered, the surface became wrinkled and sunken, and the growth was significantly inhibited. In addition, the activity of extracellular AKP, the contents of nucleic acid and extracellular protein in the bacterial suspension, relative conductivity and PI intake were significantly increased, and Na+ K+-ATPase was inactivated to a certain extent, thereby leading to cell death.

In the wake of the largest-ever recorded outbreak of mpox in terms of magnitude and geographical spread in human history since May 2022, we innovatively developed an automated online sewage virus enrichment and concentration robot for disease tracking. Coupled with an artificial intelligence (AI) model, our research aims to estimate mpox cases based on the concentration of the monkeypox virus (MPXV) in wastewater. Our research has revealed a compelling link between the levels of MPXV in wastewater and the number of clinically confirmed mpox infections, a finding that is reinforced by the ability of our AI prediction model to forecast cases with remarkable precision, capturing 87 % of the data’s variability. However, it is worth noting that this high precision in predictions may be related to the relatively high frequency of data acquisition and the relatively non-mobile isolated environment of the hospital itself. In conclusion, this study represents a significant step forward in our ability to track and respond to mpox outbreaks. It has the potential to revolutionize public health surveillance by utilizing innovative technologies for disease surveillance and prediction.

Abstract Invasive lobular breast carcinoma (ILC) is one potential subset that “clinicopathologic features” can conflict with “long-term outcome” and the optimal management strategy is unknown in such discordant situations. The present study aims to predict the long-term, overall survival (OS) and cancer-specific survival (CSS) of ILC. The clinical information of patients with non-metastatic ILC was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2020. A total of 31451 patients were enrolled and divided into the training cohort (n=22,017) and validation cohort (n=9434). The last follow-up was December, 31, 2020 and the median follow-up period was 99 months (1–203). Age, marriage, estrogen (ER) status, progesterone (PR) status, grade, tumor size, lymph node ratio (LNR) and combined summary (CS) stage were prognostic factors for both OS and CSS of ILC, whereas chemotherapy and radiation were independent protect factors for OS. The nomograms exhibited satisfactory discriminative ability. For the training and validation cohorts, the C-index of the OS nomogram was 0.765 (95% CI 0.762–0.768) and 0.757 (95% CI 0.747–0.767), and the C-index of the CSS nomogram were 0.812 (95% CI 0.804–0.820) and 0.813 (95% CI 0.799–0.827), respectively. Additionally, decision curve analysis (DCA) demonstrated that the nomograms had superior predictive performance than traditional American Joint Committee on Cancer (AJCC) TNM stage. The novel nomograms to predict long-term prognosis based on LNR are reliable tools to predict survival, which may assist clinicians in identifying high-risk patients and devising individual treatments for patients with ILC. Our findings should aid public health prevention strategies to reduce cancer burden. We provide two R/Shiny apps ( https://ilc-survival2024.shinyapps.io/osnomogram/ ; https://ilc-survival2024.shinyapps.io/cssnomogram/ ) to visualize findings.