Obovatol inhibits proliferation, invasion and immune escape of hepatocellular carcinoma cells through modulating the JAK/STST3/PD-L1 pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer that is fatal and has a dismal prognosis. Obovatol (Ob), a novel lignan derived from the leaf and stem bark of Magnolia obovata Thunb, has exhibited anti-tumor effect on diverse tumors. However, its effect and mechanisms on HCC remain to be further explored. METHODS: Huh7 and Hep3B cells, as well as BALB/c nude mice were used to determine the function and mechanisms of Ob on growth, invasion and immune escape by cell counting kit-8, transwell, enzyme-linked immunosorbent assay (ELISA) and western blot experiments. RESULTS: Ob reduced the cell viability of Huh7 and Hep3B cells, with a IC50 value of 57.41 µM and 62.86 µM, respectively. Ob declined the invasion ability, the protein expression of N-cadherin and the concentrations of IL-10 and TGF-ß, whereas increased the E-cadherin expression and the contents of IFN-γ and IL-2 in Hep3B and Huh7 cells. Mechanically, Ob decreased the protein level of p-JAK/JAK, p-STAT3/STAT3 and PD-L1, which was partly restored with the treatment of RO8191, an activator of JAK/STAT3 axis. The effect of Ob on the cell viability, the invasion ability, the protein level of N-cadherin and E-cadherin, and the concentrations of IL-10, TGF-ß, IFN-γ and IL-2 in both Hep3B and Huh7 cells was reversed with the management of RO8191. In vivo, Ob reduced tumor volume and weight, the level of N-cadherin, PD-L1, p-JAK/JAK, and p-STAT3/STAT3, with an elevated expression of E-cadherin and IFN-γ. CONCLUSION: Ob downregulated the JAK/STST3/PD-L1 pathway to attenuate the growth, invasion and immune escape of HCC.

Microbial assimilatory sulfate reduction-mediated H2S: an overlooked role in Crohn's disease development.

BACKGROUND: H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota. RESULTS: Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants ∆cysJ and ∆cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives. CONCLUSIONS: Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract.

Enhanced Low-Concentration Phosphate Adsorption Using Magnetic UiO-66@Fe3O4 Composite with Potential Linker Exchange.

A magnetic FenUiO-66 adsorbent was created to achieve high phosphate adsorption capacity. The incorporation of Fe3O4 facilitated the precipitation and growth of UiO-66 during crystallization, resulting in a shift towards a multilayer heterogeneous distribution of adsorption sites. The increased Fe3O4 content notably enhanced the magnetic properties of FenUiO-66, while negligibly affecting its adsorption performance. The Fe1.5UiO-66 demonstrated exceptional phosphate adsorption capacity (136.54 mg/g), outstanding selectivity, and sustained reusability, with an 80% removal efficiency after nine cycles of treating actual water. The mechanism of phosphate adsorption by FenUiO-66 involved electrostatic attraction, ligand exchange, and linker exchange. Notably, while linker exchange significantly contributed to high adsorption capacity, it resulted in irreversible damage to the FenUiO-66 crystal. These unequivocal findings will serve as a solid foundation for further research and underline the critical role of linkers in the process of phosphate adsorption.

Risk factors for bronchiolitis obliterans complicating adenovirus pneumonia in children: a meta-analysis.

Objective: To preliminarily explore the risk factors for post-infectious bronchiolitis obliterans (PIBO) complicating adenovirus pneumonia (ADVP) in children through a meta-analysis. Methods: A systematic search was conducted on three English-language databases (PubMed, Web of Science and The National Library of Medicine) and two Chinese-language databases (China National Knowledge Infrastructure and the Wanfang Database) between database inception and 1 January 2023. Data analysis was conducted using Stata 15.1 software. Results: A total of 10 articles, reporting 14 risk factors, were included in the analysis, with 8 risk factors taken into consideration. Through the meta-analysis, 5 risk factors were identified for PIBO complicating ADVP in paediatric patients: hypoxaemia [odds ratio (OR) = 9.37, 95% CI: 4.22, 20.77, p < 0.001], persistent wheezing (OR = 4.65, 95% CI: 2.20, 9.82, p < 0.001), mechanical ventilation (OR = 3.87, 95% CI: 2.37, 6.33, p < 0.001), length of hospital stay (LoHS) (OR = 1.25, 95% CI: 1.09, 1.43, p < 0.001) and fever duration (OR = 1.08, 95% CI: 1.02, 1.14, p = 0.009). Conclusion: Existing evidence suggests that hypoxaemia, persistent wheezing, mechanical ventilation, LoHS and fever duration are risk factors for PIBO complicating ADVP in children. These findings underscore the need for enhanced assessment and management in clinical practice. This study may provide such a clinical prediction model from the identified 5 risk factors for PIBO and offer valuable insights for preventing bronchiolitis obliterans in children with ADVP.

Liraglutide improves follicle development in polycystic ovary syndrome by inhibiting CXCL10 secretion.

BACKGROUND: At present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear. METHODS: RNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation. RESULTS: In the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation. CONCLUSIONS: The present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS. TRIAL REGISTRATION: Not applicable.

Capsaicin exerts synergistic pro-apoptotic effects with cisplatin in TSCC through the calpain pathway via TRPV1.

Capsaicin (CAP) exerts significant anti-tumor effects on a variety of tumors, with low intrinsic toxicity. Cisplatin (DDP) is currently the first-line drug for the treatment of oral cancer; however, its clinical efficacy is impeded by chemoresistance and negligible side effects. Whether the combined use of CAP and DDP has a synergistic antitumor effect on tongue squamous cell carcinoma (TSCC) cells and its underlying mechanisms remains unclear. The present study revealed that CAP reduced the activity of TSCC cells in a dose- and time-dependent manner. We also observed changes in the mitochondrial functional structure of TSCC cells, along with the induction of mitochondrial apoptosis. Moreover, when CAP was combined with DDP, a synergistic cytotoxic effect on TSCC cells was observed, which had a significant impact on inducing apoptosis, inhibiting proliferation, and disrupting the mitochondrial membrane potential in TSCC cells compared to the single-drug treatment and control groups. These effects are associated with TRPV1, a high-affinity CAP receptor. The combined use of CAP and DDP can activate the TRPV1 receptor, resulting in intracellular Ca2+ overload and activation of the calpain pathway, ultimately leading to mitochondrial apoptosis. This potential mechanism was validated in TSCC xenograft models. In conclusion, our findings clearly demonstrate that CAP exerts synergistic pro-apoptotic effects with DDP in TSCC through the calpain pathway mediated by TRPV1. Thus, CAP can be considered an effective adjuvant drug for DDP in the treatment of TSCC.

Befotertinib for patients with pretreated EGFR T790M mutated locally advanced or metastatic NSCLC: Final overall survival results from a phase 2 trial.

BACKGROUND: In the initial analysis of a pivotal phase 2 single-arm study (NCT03861156), befotertinib (D-0316) showed clinical benefit with a manageable safety profile in pretreated patients with EGFR T790M mutated non-small cell lung cancer (NSCLC), including those with brain metastases. METHODS: Eligible patients received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily until disease progression, withdrawal of informed consent, or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee. OS and safety were secondary endpoints. Herein, we present the final OS and safety data. RESULTS: A total of 176 patients in cohort A and 290 patients in cohort B were finally enrolled. At data cutoff (May 31, 2023), the median duration of follow-up was 47.9 months (95 % CI: 47.1-48.3) in cohort A and 36.7 months (35.9-37.9) in cohort B. The median OS was 23.9 months (95 % CI: 21.1-27.2) in cohort A and 31.5 months (26.8-35.3) in cohort B. The median OS for patients with and without brain metastasis in cohort A was 18.6 months (95 % CI: 14.9-26.3) and 26.4 months (95 % CI: 23.0-29.0), respectively. In cohort B, these data was 23.0 months (95 % CI: 18.6-29.1) and 35.5 months (95 % CI: 29.3-NE), respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1 % in the cohort A and 50.3 % in the cohort B, and 22.2 % and 31.7 % were related to the study drug. CONCLUSION: Befotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC.

Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.

Spinal cord injury (SCI) is a serious, disabling injury to the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the injury plane. SCI can be divided into primary injury and secondary injury according to its pathophysiological process. Primary injury is irreversible in most cases, while secondary injury is a dynamic regulatory process. Secondary injury involves a series of pathological events, such as ischemia, oxidative stress, inflammatory events, apoptotic pathways, and motor dysfunction. Among them, oxidative stress is an important pathological event of secondary injury. Oxidative stress causes a series of destructive events such as lipid peroxidation, DNA damage, inflammation, and cell death, which further worsens the microenvironment of the injured site and leads to neurological dysfunction. The nuclear factor erythrocyte 2-associated factor 2 (Nrf2) is considered to be a key pathway of antioxidative stress and is closely related to the pathological process of SCI. Activation of this pathway can effectively inhibit the oxidative stress process and promote the recovery of nerve function after SCI. Therefore, the Nrf2 pathway may be a potential therapeutic target for SCI. This review deeply analyzed the generation of oxidative stress in SCI, the role and mechanism of Nrf2 as the main regulator of antioxidant stress in SCI, and the influence of cross-talk between Nrf2 and related pathways that may be involved in the pathological regulation of SCI on oxidative stress, and summarized the drugs and other treatment methods based on Nrf2 pathway regulation. The objective of this paper is to provide evidence for the role of Nrf2 activation in SCI and to highlight the important role of Nrf2 in alleviating SCI by elucidating the mechanism, so as to provide a theoretical basis for targeting Nrf2 pathway as a therapy for SCI.

Combination of eribulin and anlotinib exerts synergistic cytotoxicity in retroperitoneal liposarcoma by inducing endoplasmic reticulum stress.

Primary retroperitoneal liposarcoma (RLPS) is a rare heterogeneous tumor occurring within retroperitoneal space, and its overall survival has not improved much in the past few decades. Based on a small-sample clinical practice at our center, patients with RLPS can greatly benefit from anlotinib and eribulin combination. In this study, we investigated the combinational effect of anlotinib and eribulin on RLPS. In vitro experiments revealed that a low dose of anlotinib significantly enhances the cytotoxic effects of eribulin, leading to a remarkable suppression of RLPS cell proliferation, viability, colony formation, migration, and cell-cycle progression compared to individual drug treatments. At the organoid level, the combination treatment causes the spheroids in Matrigel to disintegrate earlier than the single-drug group. In vivo, RLPS patient-derived xenograft (PDX) models demonstrated that the combination of these two drugs can obviously exert a safe and effective anti-tumor effect. Through transcriptome analysis, we uncovered and validated that the synergistic effect mainly is induced by the endoplasmic reticulum stress (ERS) pathway both in vitro and in vivo. Further analyses indicate that anlotinib plus eribulin treatment results in micro-vessel density and PD-L1 expression alterations, suggesting a potential impact on the tumor microenvironment. This study extensively explored the combination regimen at multiple levels and its underlying molecular mechanism in RLPS, thus providing a foundation for translational medicine research.

Metabolically healthy obesity and left ventricular geometric remodelling in Chinese children.

AIM: To investigate the association between metabolically healthy obesity (MHO) and left ventricular geometric remodelling in Chinese children. MATERIALS AND METHODS: This cross-sectional study used data from two population-based samples in China, including 2871 children aged 6-11 years. Weight status was defined based on body mass index according to the World Health Organization growth chart. Metabolic status was defined based on the 2018 consensus-based criteria proposed by Damanhoury et al. Obes Rev 2018;19:1476-1491 (blood pressure, lipids and glucose). Left ventricular geometric remodelling was determined as concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. Multinomial logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for the association between categories of weight and metabolic status and left ventricular geometric remodelling. RESULTS: Compared with children with metabolically healthy normal weight, those with MHO had higher odds of left ventricular geometric remodelling, with adjusted ORs (95% CIs) of 2.01 (1.23-3.28) for concentric remodelling, 6.36 (4.03-10.04) for eccentric hypertrophy, and 17.07 (7.97-36.58) for concentric hypertrophy. Corresponding ORs (95% CIs) were 2.35 (1.47-3.75), 10.85 (7.11-16.55), and 18.56 (8.63-39.94), respectively, for children with metabolically unhealthy obesity. In contrast, metabolically unhealthy normal weight was not associated with higher odds of left ventricular geometric remodelling. Findings were consistent in sensitivity analyses that used different definitions of weight and metabolic status and left ventricular geometric remodelling. CONCLUSIONS: Children with MHO had higher odds of left ventricular geometric remodelling than their metabolically healthy normal weight counterparts. Our findings suggest MHO may not be a benign condition for cardiac health in children.

The research on the impact of industry governance on trust after group product-harm crisis.

The group product-harm crisis has much greater and longer negative impact, and its governance has become an important issue. To address this issue, this study proposed a new construct: industry governance. On the basis of clarifying the dimensions and measurements of industry governance, this study constructed a reflective-formative hierarchical model and collected data through a questionnaire. Utilizing convenience sampling, 329 valid samples at the University in Wuhan, China collected by survey were used to verify the hypotheses. With the help of Smart PLS 3.0, this study finds that the industry governance has a significant and positive impact on consumer's trust (enterprise trust, industry trust and government trust) after the group product-harm crisis. Industry governance plays an important role in the governance of group product-harm crisis. This study is the first time to explore the structure and measurement of industry governance, and verifies the impact of industry governance on group product-harm crisis, which enriches governance theory, and perfects product-harm crisis theory, providing a new direction and guidance for managers to better manage product-harm crisis.

Maternal cigarette smoking before or during pregnancy increases the risk of severe neonatal morbidity after delivery: a nationwide population-based retrospective cohort study.

BACKGROUND: The association of maternal cigarette smoking during pregnancy with severe neonatal morbidity (SNM) is still inconclusive. We aimed to examine the associations of the timing and the intensity of maternal cigarette smoking with infant SNM in the USA. METHODS: We used birth certificate data of 12 150 535 women aged 18-49 years who had live singleton births from the 2016-2019 US National Vital Statistics System. Women self-reported the daily number of cigarettes they consumed before pregnancy and in each trimester of pregnancy. Composite SNM was defined as one or more of the following complications: assisted ventilation immediately following delivery, assisted ventilation for >6 hours, neonatal intensive care unit admission, surfactant replacement therapy, suspected neonatal sepsis, and seizure. RESULTS: Maternal cigarette smoking either before pregnancy or during any trimester of pregnancy significantly increased the risk of infant SNM, even at a very low intensity (ie, 1-2 cigarettes per day). For example, compared with women who did not smoke before pregnancy, the adjusted odds ratios and 95% confidence intervals (OR, 95% CI) of composite SNM in the newborn from women who smoked 1-2, 3-5, 6-9, 10-19, and ≥20 cigarettes per day before pregnancy were 1.16 (1.13 to 1.19), 1.22 (1.20 to 1.24), 1.26 (1.23 to 1.29), 1.27 (1.25 to 1.28), and 1.31 (1.30 to 1.33), respectively. Furthermore, smokers who stopped smoking during pregnancy still had a higher risk of composite SNM than never smokers before and throughout pregnancy. CONCLUSIONS: Maternal cigarette smoking before or during pregnancy increased the risk of infant SNM, even at a low dose of 1-2 cigarettes/day. Interventions should emphasise the detrimental effects of even light smoking before and during pregnancy.

Gut epithelial electrical cues drive differential localization of enterobacteria.

Salmonella translocate to the gut epithelium via microfold cells lining the follicle-associated epithelium (FAE). How Salmonella localize to the FAE is not well characterized. Here we use live imaging and competitive assays between wild-type and chemotaxis-deficient mutants to show that Salmonella enterica serotype Typhimurium (S. Typhimurium) localize to the FAE independently of chemotaxis in an ex vivo mouse caecum infection model. Electrical recordings revealed polarized FAE with sustained outward current and small transepithelial potential, while the surrounding villus is depolarized with inward current and large transepithelial potential. The distinct electrical potentials attracted S. Typhimurium to the FAE while Escherichia coli (E. coli) localized to the villi, through a process called galvanotaxis. Chloride flux involving the cystic fibrosis transmembrane conductance regulator (CFTR) generated the ionic currents around the FAE. Pharmacological inhibition of CFTR decreased S. Typhimurium FAE localization but increased E. coli recruitment. Altogether, our findings demonstrate that bioelectric cues contribute to S. Typhimurium targeting of specific gut epithelial locations, with potential implications for other enteric bacterial infections.

Small RNA-Seq and real time rt-qPCR reveal islet miRNA released under stress conditions.

Replacement of beta cells through transplantation is a potential therapeutic approach for individuals with pancreas removal or poorly controllable type 1 diabetes. However, stress and death of beta cells pose significant challenges. Circulating miRNA has emerged as potential biomarkers reflecting early beta cell stress and death, allowing for timely intervention. The aim of this study was to identify miRNAs as potential biomarkers for beta cell health. Literature review combined with small RNA sequencing was employed to select islet-enriched miRNA. The release of those miRNA was assessed by RT-qPCR in vivo, using a streptozotocin induced diabetes mouse model and in vitro, through mouse and human islets exposed to varying degrees of hypoxic and cytokine stressors. Utilizing the streptozotocin induced model, we identified 18 miRNAs out of 39 candidate islet-enriched miRNA to be released upon islet stress in vivo. In vitro analysis of culture supernatants from cytokine and/or hypoxia stressed islets identified the release of 45 miRNAs from mouse and 8 miRNAs from human islets. Investigation into the biological pathways targeted by the cytokine- and/or hypoxia-induced miRNA suggested the involvement of MAPK and PI3K-Akt signaling pathways in both mouse and human islets. We have identified miRNAs associated with beta cell health and stress. The findings allowed us to propose a panel of 47 islet-related human miRNA that is potentially valuable for application in clinical contexts of beta cell transplantation and presymptomatic early-stage type 1 diabetes.

Associations between antibacterial mouthwash use with sexual behaviours and sexually transmitted infections among Chinese men who have sex with men: a cross-sectional study.

Background Mouthwash is a commonly used product with the potential to prevent STIs. This study aimed to determine the association between mouthwash use frequency with sexual behaviours and STIs among Chinese men who have sex with men (MSM). Methods A cross-sectional study was conducted among MSM in Xi'an, China, from January to September 2022. Participants were categorised into non-mouthwash users, occasional (used it less than once every week) and frequent (used it more than once every week) mouthwash users. Multinomial logistic regression was performed to identify the association between mouthwash use frequency with sexual behaviours. Results Of 838 MSM included in the analysis, 621 (74.11%) reported never using mouthwash, whereas 47 (5.60%) used it occasionally and 170 (20.29%) used it frequently. Frequent mouthwash users had a lower prevalence of chlamydia compared with occasional users (8.33% vs 23.93%, P Conclusion MSM with more sexual partners or lower condom use frequency were more likely to be frequent mouthwash users. However, frequent mouthwash users had a lower chlamydia prevalence.

Investigations on the shock wave induced by collapse of a toroidal bubble.

When bubbles collapse near a wall, they typically experience an asymmetric deformation. This collapse leads to the creation of a jet that strikes the bubble interface, causing the formation of a toroidal bubble and the subsequent release of a water-hammer shock. In this study, we present a systematic analysis of the collapse of a toroidal bubble in an open field or adjacent to a flat wall using high-fidelity numerical simulation. To maintain the sharpness of the interface, we employ the interface compression technique and the boundary variation diminishing approach within the two-phase model. Our findings demonstrate that shock waves emitted from the toroidal bubble consistently propagate toward the central axis of the torus, resulting in significant pressure shocks along the axis, similar to the water-hammer shock formed during the collapse of a spherical bubble. In contrast, weak pressure waves are generated in the transverse directions, leading to relatively weaker pressure peaks. Furthermore, the wall-pressure peak induced by the toroidal bubble is approximately three times higher than that induced by the spherical bubble. Based on the directional characteristics of pressure wave propagation from collapsing toroidal bubbles, toroidal-shaped pressure vessels can be designed as buoyancy materials for deep submersibles. This design enables the focused release of energy in a specific direction, effectively minimizing the destructive chain reaction caused by the implosion.

Advanced membrane-based high-value metal recovery from wastewater.

Considering the circular economy and environmental protection, sustainable recovery of high-value metals from wastewater has become a prominent concern. Unlike conventional methods featuring extensive chemicals or energy consumption, membrane separation technology plays a crucial role in facilitating the sustainable and efficient recovery of valuable metals from wastewater due to its attractive features. In this review, we first briefly summarize the sustainable supply chain and significance of sustainable recovery of aqueous high-value metals. Then, we review the most recent advances and application potential in promising state-of-the-art membrane-based technologies for recovery of high-value metals (silver, gold, rhenium, platinum, ruthenium, palladium, iridium, osmium, and rhodium) from wastewater effluents. In particular, pressure-based membranes, liquid membranes, membrane distillation, forward osmosis, electrodialysis and membrane-based hybrid technologies and their mechanism of high-value metal recovery is thoroughly discussed. Then, engineering application and economic sustainability are also discussed for membrane-based high-value metal recovery. The review finally concludes with a critical and insightful overview of the techno-economic viability and future research direction of membrane technologies for efficient high-value metal recovery from wastewater.

Hypoxia activates macrophage-NLRP3 inflammasome promoting atherosclerosis via PFKFB3-driven glycolysis.

The onset and progression of atherosclerosis are closely linked to the involvement of macrophages. While the contribution of NLRP3 inflammasome activation to the creation of a local highly inflammatory microenvironment is well recognized, the precise triggers remain unclear. In this study, we aimed to investigate the regulatory mechanism of NLRP3 inflammasome activation in response to hypoxia-induced glycolysis involving PFKFB3 in the development of atherosclerosis. To develop an atherosclerosis model, we selected ApoE knockout mice treated with a high-fat western diet. We then quantified the expression of HIF-1α, PFKFB3, and NLRP3. In addition, we administered the PFKFB3 inhibitor PFK158 during atherosclerosis modeling. The glycolytic activity was subsequently determined through 18F-FDG micro-PET/CT, ex vivo glucose uptake, and ECAR analysis. Furthermore, we employed lipopolysaccharide (LPS) and TNF-α to induce the differentiation of bone marrow-derived macrophages (BMDMs) into M1-like phenotypes under both hypoxic and normoxic conditions. Our histological analyses revealed the accumulation of PFKFB3 in human atherosclerotic plaques, demonstrating colocalization with NLRP3 expression and macrophages. Treatment with PFK158 reduced glycolytic activity and NLRP3 inflammasome activation, thereby mitigating the occurrence of atherosclerosis. Mechanistically, hypoxia promoted glycolytic reprogramming and NLRP3 inflammasome activation in BMDMs. Subsequent blocking of either HIF-1α or PFKFB3 downregulated the NLRP3/Caspase-1/IL-1ß pathway in hypoxic BMDMs. Our study demonstrated that the HIF-1α/PFKFB3/NLRP3 axis serves as a crucial mechanism for macrophage inflammation activation in the emergence of atherosclerosis. The therapeutic potential of PFKFB3 inhibition may represent a promising strategy for atheroprotection.

Quantifying the pollution changes and meteorological dependence of airborne trace elements coupling source apportionment and machine learning.

Airborne trace elements (TEs) present in atmospheric fine particulate matter (PM2.5) exert notable threats to human health and ecosystems. To explore the impact of meteorological conditions on shaping the pollution characteristics of TEs and the associated health risks, we quantified the variations in pollution characteristics and health risks of TEs due to meteorological impacts using weather normalization and health risk assessment models, and analyzed the source-specific contributions and potential sources of primary TEs affecting health risks using source apportionment approaches at four sites in Shandong Province from September to December 2021. Our results indicated that TEs experience dual effects from meteorological conditions, with a tendency towards higher TE concentrations and related health risks during polluted period, while the opposite occurred during clean period. The total non-carcinogenic and carcinogenic risks of TEs during polluted period increased approximately by factors of 0.53-1.74 and 0.44-1.92, respectively. Selenium (Se), manganese (Mn), and lead (Pb) were found to be the most meteorologically influenced TEs, while chromium (Cr) and manganese (Mn) were identified as the dominant TEs posing health risks. Enhanced emissions of multiple sources for Cr and Mn were found during polluted period. Depending on specific wind speeds, industrialized and urbanized centers, as well as nearby road dusts, could be key sources for TEs. This study suggested that attentions should be paid to not only the TEs from primary emissions but also the meteorology impact on TEs especially during pollution episodes to reduce health risks in the future.

The Impact of Death Education on College 'Students' Sense of Meaning in Life and Ability to Cope with Death.

Purpose: This study aims to assess the impact of death education on college students' sense of meaning in life and ability to cope with death. Method: A questionnaire survey was conducted among a randomly selected sample of 320 undergraduate students from a specific city. The survey, administered through the paper questionnaire, collected data on students' demographic characteristics, their awareness of death, and their demand for death education. Linear regression analysis was performed to identify factors influencing the demand for death education and assess its impact on college students' attitudes towards death, sense of meaning in life, and coping abilities. Results: The results revealed that participants' personality traits and family status significantly influenced their need for death education (P < .05). The overall score for death education needs among participants was (37.40±6.57). Notably, the statement "I think death education can help me understand death" received the highest mean rating (3.85), while the statement "I think death education will help me engage in nursing work in the future" received the lowest mean rating (3.55). Personal factors such as personality, family status, being an only child, and family experiences with serious illness were found to impact college students' demand for death education (P < .05). Post-death education, significant differences were observed in scores related to death fear and escape acceptance dimensions (P < .05). Moreover, there were statistically significant improvements in students' sense of meaning in life, quality of life, and life goals following death education (P < .05). Additionally, all dimensions of death coping ability showed higher scores after death education (P < .05). Factors such as current psychological state, being an only child, family experiences with serious illness, and attendance at funerals were found to be statistically significant in relation to college students' sense of meaning in life (P < .05). Multiple regression analysis indicated that the sense of meaning in life was influenced by the current psychological state and family experiences with serious illness (P < .05). Conclusion: The study highlights the importance of integrating death education into college curriculums to address students' fear of death and enhance their appreciation of life. Providing death education can help students develop a healthier perspective on death, improve their well-being, reduce avoidance attitudes towards death-related events, and strengthen their sense of meaning in life and ability to cope with death. These findings emphasize the need for educational institutions to implement comprehensive death education programs, considering individual factors such as personality and family background, and contribute to the development of effective educational policies and curricula.