Mechanisms of conjugative transfer of antibiotic resistance genes induced by extracellular polymeric substances: Insights into molecular diversities and electron transfer properties.

Dissemination of antibiotic resistance genes (ARGs) has become a critical threat to public health. Activated sludge, rich in extracellular polymeric substances (EPS), is an important pool of ARGs. In this study, mechanisms of conjugation transfer of ARGs induced by EPS, including tightly bound EPS (TBEPS), soluble EPS (SEPS), and loosely bound EPS (LBEPS), were explored in terms of molecular diversities and electron transfer properties of EPS. Conjugation transfer frequency was increased by 9.98-folds (SEPS), 4.21-folds (LBEPS), and 15.75-folds (TBEPS) versus the control, respectively. Conjugation-related core genes involving SOS responses (9 genes), membrane permeability (18 genes), intercellular contact (17 genes), and energy metabolism pathways (13 genes) were all upregulated, especially in the presence of TBEPS. Carbohydrates and aliphatic substances in SEPS and LBEPS were contributors to ARG transfer, via influencing reactive oxygen species (ROS) formation (SEPS) and ROS and adenosine triphosphate (ATP) production (LBEPS). TBEPS had the highest redox potential and greatest lability and facilitated electron transfer and alternated respiration between cells, thus promoting ARG transfer by producing ATP. Generally, the chemical molecular characteristics and redox properties of EPS facilitated ARG transfer mainly by influencing lipid peroxidation and ATP, respectively.

Luteolin protects mouse hippocampal neuronal cells against isoflurane-induced neurotoxicity through miR-214/PTEN/Akt pathway.

Isoflurane is one of the most commonly used anaesthetic agents in surgery procedures. During the past decades, isoflurane has been found to cause impairment in neurological capabilities in new-borns and elderly patients. Luteolin is a flavonoid that has been documented to possess a neuroprotective effect. Here we investigated the putative neuroprotective effects of luteolin on isoflurane-induced neurotoxicity in mouse hippocampal neuronal HT22 cells and explored the potential mechanisms. We demonstrated that luteolin improved mitochondrial dysfunction and reduced oxidative stress and apoptosis in isoflurane-treated HT22 cells, and thus inhibiting the isoflurane-induced neuronal injury. Further investigations showed that isoflurane exposure caused miR-214 downregulation, which could be mitigated by treatment with luteolin. Knockdown of miR-214 attenuated the neuroprotection of luteolin on isoflurane-induced neuronal injury. More importantly, luteolin inhibited isoflurane-caused regulation of the PTEN/Akt pathway, while miR-214 knockdown altered the regulatory effect of luteolin on the PTEN/Akt pathway. Furthermore, the effects of miR-214 knockdown on the neuroprotection of luteolin could also be prevented by knockdown of PTEN, implying that the neuroprotective effect of luteolin was mediated by miR-214/PTEN/Akt signaling pathway. These findings provided evidence for the potential application of luteolin in preventing isoflurane-induced neurotoxicity.

The relationship between parental support for exercise and depression: The mediating effects of physical exercise and physical self-esteem.

The mental health challenges among Chinese college students have become a pressing social concern. This study examined the relationship between parental support for exercise and depression among freshmen and also explored the mediating role of physical exercise and physical self-esteem. Utilizing the Parental Exercise Support Scale, Depression Self-Rating Scale, Physical Activity Rating Scale, and Physical Self-Esteem Scale, a questionnaire survey was conducted. Convenient samples from two universities were recruited by university teachers, which included 766 university freshmen. Correlation and linear regression analyses were employed to assess the overall associations while bootstrapping method was used to test mediation effects. Results indicated significant correlations between parental support for exercise and physical exercise, physical self-esteem, and depression. Physical exercise and physical self-esteem were found to mediate the relationship between parental support for exercise and depression, both individually and sequentially. These findings highlight the potential association between parental support for exercise and the mental health of college freshmen and also offer a mechanism to understand this association.

Mechanochemical Synthesis of Silylcyclopentenes via Ball Milling.

The development of innovative methods for synthesizing silylcyclopentene compounds is particularly important for enriching and improving the synthetical toolbox of organosilicon compounds. Herein, a facile approach has been developed for the synthesis of silylcyclopentenes promoted by mechanochemically generated organolithium species as silicon nucleophiles under ball milling conditions, avoiding the requirement of large amounts of bulk solvent. This operationally simple method demonstrates good functional group compatibility, which provides a great opportunity for further exploration of the synthetic applications of silylcyclopentenes. Density functional theory calculations indicated that the transient lithiosilole intermediates undergo a stepwise nucleophilic addition process, which governs this mechanic-force-promoted [4+1] cycloaddition reaction.

Organophotocatalyzed Cross Coupling of C- and Si-Radical to Access Dibenzylic Silanes from para-Quinone Methides and Silanecarboxylic Acids.

Herein we present a catalytic cross-coupling strategy between C-radicals and Si-radicals, enabling the efficient, gentle, and versatile synthesis of dibenzylic silanes from para-quinone methides and silanecarboxylic acids as the stable silyl radical precursors. The reaction is facilitated by an inexpensive organophotocatalyst and exhibits broad compatibility with various electron-donating and electron-withdrawing functional groups. Notably, mechanistic investigations suggest the involvement of dibenzylic and silyl radicals, underscoring a novel radical coupling mechanism that introduces a fresh perspective on C-Si bond formation.

Targeted discovery of unusual diterpenoids with anti-fungal activity from the root of Euphorbia lathyris.

Lathyrisone A (1), a diterpene with an undescribed tricyclic 6/6/6 fused carbon skeleton, along with spirolathyrisins B-D (3-5), three diterpenes with a rare [4.5.0] spirocyclic carbon skeleton, and one known compound (2) were isolated from the roots of Euphorbia lathyris. Their chemical structures were characterized by extensive spectroscopic analysis, X-ray crystallography, ECD and quantum chemistry calculation. A plausible biosynthetic pathway for compounds 1-5 was proposed, which suggested it is a competitive pathway for ingenol biosynthesis in the plant. The anti-fungal activities of these compounds were tested, especially, compound 2 showed stronger anti-fungal activities against Fusarium oxysporum and Alternaria alternata than the positive control fungicide thiophanate-methyl. The preliminary structure-activity relationship of compounds 1-5 was also discussed. These results not only expanded the chemical diversities of E. lathyris, but also provided a lead compound for the control of plant pathogens.

High-Throughput Growth of Armored Perovskite Single Crystal Fibers for Pixelated Arrays.

The poor machinability of halide perovskite crystals severely hampered their practical applications. Here a high-throughput growth method is reported for armored perovskite single-crystal fibers (SCFs). The mold-embedded melt growth (MEG) method provides each SCF with a capillary quartz shell, thus guaranteeing their integrality when cutting and polishing. Hundreds of perovskite SCFs, exemplified by CsPbBr3, CsPbCl3, and CsPbBr2.5I0.5, with customized dimensions (inner diameters of 150-1000 µm and length of several centimeters), are grown in one batch, with all the SCFs bearing homogeneity in shape, orientation, and optical/electronic properties. Versatile assembly protocols are proposed to directly integrate the SCFs into arrays. The assembled array detectors demonstrated low-level dark currents (< 1 nA) with negligible drift, low detection limit (< 44.84 nGy s-1), and high sensitivity (61147 µC Gy-1 cm-2). Moreover, the SCFs as isolated pixels are free of signal crosstalk while showing uniform X-ray photocurrents, which is in favor of high spatial resolution X-ray imaging. As both MEG and the assembly of SCFs involve none sophisticated processes limiting the scalable fabrication, the strategy is considered to meet the preconditions of high-throughput productions.

Biomechanical Effect of Different Posterior Fixation Techniques on Stability and Adjacent Segment Degeneration in Treating Thoracolumbar Burst Fracture With Osteoporosis: A Finite Element Analysis.

STUDY DESIGN: Finite element analysis. OBJECTIVE: To investigate the biomechanical effect of four posterior fixation techniques on stability and adjacent segment degeneration in treating thoracolumbar burst fractures with osteoporosis. SUMMARY OF BACKGROUND DATA: In terms of stability and adjacent segment degeneration, there remains no consensus or guidelines on the optimal technique for the treatment of thoracolumbar burst fractures in patients with osteoporosis. MATERIALS AND METHODS: Images of CT scans were imported into MIMICS and further processed by Geomagic to build three-dimensional models of the T10-L5 region. A v-shaped osteotomy was performed on the L1 vertebral body to simulate a burst fracture in the setting of osteoporosis. Subsequently, four fixation techniques were designed using SolidWorks software. Range of motion (ROM) of the global spine, ROM distribution, ROM of adjacent segment, Von Mises stress on adjacent intervertebral disks, and facet joints were analyzed. RESULTS: Among the four groups, the cortical bone screw fixation (CBT) showed the highest global ROM at 1.86°, while long-segmented pedicle screw fixation (LSPS) had the lowest global ROM at 1.25°. The LSPS had the smallest percentage of ROM of fractured vertebral body to fixed segment at 75.04%, suggesting the highest stability after fixation. The maximum ROM of the adjacent segment was observed in the CBT at 1.32°, while the LSPS exhibited the smallest at 0.89°. However, the LSPS group experienced larger maximum stress on the adjacent intervertebral disks (9.60 MPa) and facet joints (3.36 MPa), indicating an increasing risk of adjacent segment disease. CONCLUSION: LSPS provided the greatest stability, while CBT provided the smallest amount of stability. However, the elevated stress on adjacent intervertebral disks and facet joints after LSPS fixation increased the possibility of adjacent segment degeneration. Cement-augmented pedicle screw fixation (CAPS) and combined cortical bone screw and pedicle screw fixation (CBT-PS) demonstrated significant biomechanical advantages in providing moderate fixation strength while reducing stress on the intervertebral disks and facet joints.

Study on fingerprint and quantitative analysis of Verbena officinalis water extract by LC-MS and HPLC.

Verbena officinalis L. as a medical plant has been used to treat many diseases. However, the quality control underlying V. officinalis remains to be studied. HPLC fingerprint analysis and the qualitative and quantitative analysis of water extract from V. officinalis were carried out, and it was found that the quality varies according to habitat and batch. Verbenalin could be a crucial component in the quality evaluation of V. officinalis. This study contributes to better understanding of quality control for V. officinalis.

Segmentation of the left atrial appendage based on fusion attention.

In clinical practice, the morphology of the left atrial appendage (LAA) plays an important role in the selection of LAA closure devices for LAA closure procedures. The morphology determination is influenced by the segmentation results. The LAA occupies only a small part of the entire 3D medical image, and the segmentation results are more likely to be biased towards the background region, making the segmentation of the LAA challenging. In this paper, we propose a lightweight attention mechanism called fusion attention, which imitates human visual behavior. We process the 3D image of the LAA using a method that involves overview observation followed by detailed observation. In the overview observation stage, the image features are pooled along the three dimensions of length, width, and height. The obtained features from the three dimensions are then separately input into the spatial attention and channel attention modules to learn the regions of interest. In the detailed observation stage, the attention results from the previous stage are fused using element-wise multiplication and combined with the original feature map to enhance feature learning. The fusion attention mechanism was evaluated on a left atrial appendage dataset provided by Liaoning Provincial People's Hospital, resulting in an average Dice coefficient of 0.8855. The results indicate that the fusion attention mechanism achieves better segmentation results on 3D images compared to existing lightweight attention mechanisms.

HDAC inhibitors as a potential therapy for chemotherapy-induced neuropathic pain.

Cancer, a chronic disease characterized by uncontrolled cell development, kills millions of people globally. The WHO reported over 10 million cancer deaths in 2020. Anticancer medications destroy healthy and malignant cells. Cancer treatment induces neuropathy. Anticancer drugs cause harm to spinal cord, brain, and peripheral nerve somatosensory neurons, causing chemotherapy-induced neuropathic pain. The chemotherapy-induced mechanisms underlying neuropathic pain are not fully understood. However, neuroinflammation has been identified as one of the various pathways associated with the onset of chemotherapy-induced neuropathic pain. The neuroinflammatory processes may exhibit varying characteristics based on the specific type of anticancer treatment delivered. Neuroinflammatory characteristics have been observed in the spinal cord, where microglia and astrocytes have a significant impact on the development of chemotherapy-induced peripheral neuropathy. The patient's quality of life might be affected by sensory deprivation, loss of consciousness, paralysis, and severe disability. High cancer rates and ineffective treatments are associated with this disease. Recently, histone deacetylases have become a novel treatment target for chemotherapy-induced neuropathic pain. Chemotherapy-induced neuropathic pain may be treated with histone deacetylase inhibitors. Histone deacetylase inhibitors may be a promising therapeutic treatment for chemotherapy-induced neuropathic pain. Common chemotherapeutic drugs, mechanisms, therapeutic treatments for neuropathic pain, and histone deacetylase and its inhibitors in chemotherapy-induced neuropathic pain are covered in this paper. We propose that histone deacetylase inhibitors may treat several aspects of chemotherapy-induced neuropathic pain, and identifying these inhibitors as potentially unique treatments is crucial to the development of various chemotherapeutic combination treatments.

Vertically Oriented Perovskites with Minimized Intrinsic Boundaries for Efficient Photovoltaics.

Intrinsic boundaries formed by grain stacks of randomly oriented perovskite crystallites seriously restrict charge transport in the resultant photovoltaic devices, whereas direct passivation of these defects remains unexplored, and it is desirable to modulate perovskite growth with uniform orientation. Herein, we report a simple but effective method to regulate perovskite crystallization by employing a volatile and polymerizable monomer of hydroxyethyl methacrylate (HEMA), which can simultaneously interact with both FA+ and Pb2+ via hydrogen and coordination bonding, respectively, to seed perovskite crystallization with accelerated nucleation and retarded crystal growth. Upon thermal annealing, the gradual volatilization and partial self-condensation of the HEMA drive the perovskite growth perpendicularly to the substrate, leading to largely suppressed defect states, improved crystallinity, and a reduced Young's modulus of the perovskite film. As a result, champion efficiencies exceeding 24 and 22% with improved operational and mechanical stability of the optimized perovskite solar cells based on rigid and flexible substrates were finally achieved.

Prognostic Risk Models Using Epithelial Cells Identify ß-Sitosterol as a Potential Therapeutic Target Against Esophageal Squamous Cell Carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive and fatal malignancy that leads to epithelial cancer. The association between epithelial cell heterogeneity, prognosis, and immune response in this cancer remains uncertain. This study aimed to investigate epithelial cell heterogeneity in ESCC and develop a predictive risk model using the identified cell types. Methods: Single-cell RNA sequencing (scRNA-seq) and differential ESCC gene data were accessed from the Gene Expression Omnibus. Functional enrichment analysis, inferCNV, cell development trajectories, and intercellular communication were analyzed following epithelial cell characterization. Differentially expressed ESCC (n = 773) and epithelial cell marker genes (n = 3407) were intersected to obtain core genes, and epithelial cell-related prognostic genes were identified. LASSO regression analysis was used to construct a prognostic model. The external dataset GSE53624 was used to further validate the stability of the model. Drug sensitivity predictions, and immune cell infiltration were analyzed. Molecular docking clarified the possible therapeutic role of ß-sitosterol in ESCC. Finally, wound healing assay, cell colony, and transwell assay were constructed to detect the effects of the core gene PDLIM2 on ESCC cell proliferation, invasion, and migration. Results: Eight cell clusters were identified, and epithelial cells were categorized into tumor and paratumor groups. The tumor group possessed more chromosomal variants than the paratumor group. Epithelial cells were associated with multiple cell types and significantly correlated with the Wnt, transforming growth factor, and epidermal growth factor signaling pathways. From 231 intersected genes, five core genes were screened for use in the risk model: CTSL, LAPTM4B, MYO10, NCF2, and PDLIM2. These genes may contribute to the cancerous transformation of normal esophageal epithelial cells and thereby act as biomarkers and potential therapeutic targets in patients with ESCC. ß-Sitosterol furthermore displayed excellent docking potential with these genes. Meanwhile, further experiments demonstrated that the gene PDLIM2 plays a major role in the progression of oesophageal squamous carcinoma. Conclusion: We successfully developed a risk model for the prognosis of ESCC based on epithelial cells that addresses the response of ESCC to immunotherapy and offers novel cancer treatment options.

What is hindering Chinese women from participating in combat sports?

With the awakening of female consciousness, women's participation in sports has gradually gained autonomy and agency. However, Chinese women still face numerous restrictions in combat sports, hindering the development of this industry. Based on years of practice and research experience in the field, we summarize some general and specific issues, such as stigmatization and the constraints of traditional Chinese thinking. These issues need attention and consideration in the pursuit of gender equality in sports in the future.

Continuous Flow Electrochemical Synthesis of Olivine-Structured NaFePO4 Cathode Material for Sodium-Ion Batteries from Recycle LiFePO4.

To mitigate the environmental impact of the improper disposal of spent LiFePO4 batteries and reduce resource waste, the development of LiFePO4 recycling technologies is of paramount importance. Meanwhile, olivine-structured NaFePO4 in sodium-ion batteries has received great attention, due to its high theoretical specific capacity of 154 mAh g-1 and excellent stability. However, olivine NaFePO4 only can be synthesized from olivine LiFePO4. Accordingly, in this proposal, developing the continuous flow electrochemical solid-liquid reactor-based metal ion insertion technology is to utilize the olivine FePO4, recycled from LiFePO4, and to synthesize NaFePO4. Additionally, by employing I- as the reducing agent, NaFePO4 is successfully synthesized with a discharge-specific capacity of 134 mAh g-1 at 0.1C and a remarkable capacity retention rate of 86.5% after 100 cycles at 0.2C. And the reasons for sodium deficiency in the synthesized NFP are elucidated through first-principles calculations. Furthermore, the kinetics of the solid-solution reaction 2 (Na2/3+ßPO4→ Na1-αFePO4) mechanism improve with cycling and are sensitive to temperature. Utilizing a minimal amount of reducing agent in the electrochemical reactor, NaFePO4 synthesis is successfully achieved. This innovative approach offers a new, cost-effective, and environmentally friendly strategy for preparing NaFePO4 from recycling LiFePO4.

Nature connectedness connects the visibility of trees through windows and mental wellbeing: a study on the "3 visible trees" component of the 3-30-300 rule.

To examine the mediatory role of nature connectedness between tree visibility through windows and mental wellbeing, we conducted a questionnaire survey and examined the mediation effect using both cross-sectional and semi-longitudinal mediation models. We evaluated nature connectedness using the Inclusion of Nature in Self (INS) scale and the Connectedness to Nature Scale (CNS) and measured mental wellbeing using the WHO-5 wellbeing index. Our results showed that participants who could see at least three trees through their windows reported higher levels of both nature connectedness and mental wellbeing compared to those without such visibility. Nature connectedness significantly mediated the relationship between the visibility of trees through windows and mental wellbeing, albeit with a somewhat limited effect. More broadly, this study provides additional evidence in support of the "3" component of the 3-30-300 "rule" for equitable access to greenspace in cities.

Multi-tissue profiling of oxylipins reveal a conserved up-regulation of epoxide:diol ratio that associates with white adipose tissue inflammation and liver steatosis in obesity.

BACKGROUND: Obesity drives maladaptive changes in the white adipose tissue (WAT) which can progressively cause insulin resistance, type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated liver disease (MASLD). Obesity-mediated loss of WAT homeostasis can trigger liver steatosis through dysregulated lipid pathways such as those related to polyunsaturated fatty acid (PUFA)-derived oxylipins. However, the exact relationship between oxylipins and metabolic syndrome remains elusive and cross-tissue dynamics of oxylipins are ill-defined. METHODS: We quantified PUFA-related oxylipin species in the omental WAT, liver biopsies and plasma of 88 patients undergoing bariatric surgery (female N = 79) and 9 patients (female N = 4) undergoing upper gastrointestinal surgery, using UPLC-MS/MS. We integrated oxylipin abundance with WAT phenotypes (adipogenesis, adipocyte hypertrophy, macrophage infiltration, type I and VI collagen remodelling) and the severity of MASLD (steatosis, inflammation, fibrosis) quantified in each biopsy. The integrative analysis was subjected to (i) adjustment for known risk factors and, (ii) control for potential drug-effects through UPLC-MS/MS analysis of metformin-treated fat explants ex vivo. FINDINGS: We reveal a generalized down-regulation of cytochrome P450 (CYP)-derived diols during obesity conserved between the WAT and plasma. Notably, epoxide:diol ratio, indicative of soluble epoxide hydrolyse (sEH) activity, increases with WAT inflammation/fibrosis, hepatic steatosis and T2DM. Increased 12,13-EpOME:DiHOME in WAT and liver is a marker of worsening metabolic syndrome in patients with obesity. INTERPRETATION: These findings suggest a dampened sEH activity and a possible role of fatty acid diols during metabolic syndrome in major metabolic organs such as WAT and liver. They also have implications in view of the clinical trials based on sEH inhibition for metabolic syndrome. FUNDING: Wellcome Trust (PS3431_WMIH); Duke-NUS (Intramural Goh Cardiovascular Research Award (Duke-NUS-GCR/2022/0020); National Medical Research Council (OFLCG22may-0011); National Institute of Environmental Health Sciences (Z01 ES025034); NIHR Imperial Biomedical Research Centre.

Four lathyrane diterpenoids from the seeds of Euphorbia lathyris.

Four new diterpenoids, including three secolathyrane diterpenoids (1-3) and one lathyrane diterpenoid (4), together with seven known diterpenoids, were obtained in the shelled seeds of Euphorbia lathyris. In particular, 1-3 possess a rare split ring structure, and currently only one compound with the same skeleton has been identified in E. lathyris. Compound 4 furnishes an unprecedented oxygen bridge structure. The structures were identified using various spectral techniques, including NMR, HR-ESI-MS, single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD). The biosynthetic pathway of 1-4 was inferred. Furthermore, the cytotoxic activities of all compounds (1-11) were measured on three human tumor cells. New compounds 2 and 3 showed moderate cytotoxic activities against U937 cells with IC50 values of 22.18 and 25.41 µM, respectively.

A novel HDAC6 inhibitor attenuate APAP-induced liver injury by regulating MDH1-mediated oxidative stress.

Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.