Diosmetin-7-O-ß-D-glucopyranoside from Pogostemonis Herba alleviated SARS-CoV-2-induced pneumonia by reshaping macrophage polarization and limiting viral replication.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.

Raloxifene Prevents Chemically-Induced Ferroptotic Neuronal Death In Vitro and In Vivo.

Ferroptosis, a regulated form of cell death characterized by excessive iron-dependent lipid peroxidation, can be readily induced in cultured cells by chemicals such as erastin and RSL3. Protein disulfide isomerase (PDI) has been identified as an upstream mediator of chemically induced ferroptosis and also a target for ferroptosis protection. In this study, we discovered that raloxifene (RAL), a selective estrogen receptor modulator known for its neuroprotective actions in humans, can effectively inhibit PDI function and provide robust protection against chemically induced ferroptosis in cultured HT22 neuronal cells. Specifically, RAL can bind directly to PDI both in vitro and in intact neuronal cells and inhibit its catalytic activity. Computational modeling analysis reveals that RAL can tightly bind to PDI through forming a hydrogen bond with its His256 residue, and biochemical analysis further shows that when PDI's His256 is mutated to Ala256, RAL loses its inhibition of PDI's catalytic activity. This inhibition of PDI by RAL significantly reduces the dimerization of both the inducible and neuronal nitric oxide synthases and the accumulation of nitric oxide, both of which have recently been shown to play a crucial role in mediating chemically induced ferroptosis through subsequent induction of ROS and lipid-ROS accumulation. In vivo behavioral analysis shows that mice treated with RAL are strongly protected against kainic acid-induced memory deficits and hippocampal neuronal damage. In conclusion, this study demonstrates that RAL is a potent inhibitor of PDI and can effectively prevent chemically induced ferroptosis in hippocampal neurons both in vitro and in vivo. These findings offer a novel estrogen receptor-independent mechanism for RAL's neuroprotective actions in animal models and humans.

Diosmetin Promotes Early Embryonic Development in Pigs by Alleviating Oxidative Stress.

Diosmetin (DIOS), a natural flavonoid monomer derived from lemons and present in various plants such as spearmint and spider moss, exhibits antioxidant, anti-inflammatory, and antiaging properties. Nonetheless, its impact on early embryonic development in pigs remains unexplored. This study aimed to determine the influence of DIOS supplementation in an in vitro culture (IVC) medium on porcine embryo development and to elucidate the underlying mechanisms. Findings revealed that embryos cultured in IVC medium with 0.1 µM DIOS demonstrated an increased blastocyst formation rate, higher total cell number, reduced LC3B and CASPASE3 levels, elevated Nrf2 levels, decreased ROS, and enhanced GSH and mitochondrial membrane potential at the 4-cell embryonic stage. Additionally, the expression of proapoptotic genes (CAS3, CAS8, and BAX) and autophagy-related genes (BECLIN1, ATG5, LC3B, and P62) was downregulated, whereas the expression of embryonic development-related genes (CDK1 and CDK2), antioxidant-related genes (SOD1 and SOD2), and mitochondrial biogenesis-related genes (NRF2) was upregulated. These findings suggest that DIOS promotes early embryonic development in pigs by mitigating oxidative stress and enhancing mitochondrial function, thereby reducing autophagy and apoptosis levels.

Decoding the genomic enigma: Approaches to studying extrachromosomal circular DNA.

Extrachromosomal circular DNA (eccDNA), a pervasive yet enigmatic component of the eukaryotic genome, exists autonomously from its chromosomal counterparts. Ubiquitous in eukaryotes, eccDNA plays a critical role in the orchestration of cellular processes and the etiology of diseases, particularly cancers. However, the full scope of its influence on health and disease remains elusive, presenting a rich vein of research yet to be mined. Unraveling the complexities of eccDNA necessitates a distillation of methodologies - from biogenesis to functional analysis - a landscape we overview in this study with precision and clarity. Here, we systematically outline cutting-edge methodologies from high-throughput sequencing and bioinformatics to experimental validations, showcasing the intricate world of eccDNAs. We combed through a treasure trove of auxiliary research resources and analytical tools. Moreover, we chart a course for future inquiry, illuminating the horizon with potential groundbreaking strategies for designing eccDNA research projects and pioneering new methodological frontiers.

Cu(I)-Induced 'Click Reaction' Involving Coordination and Covalent Assembly of Hybrid Borates for the Electrocatalytic CO2 Reduction.

The design and synthesis of hybrid borates by the organic ligand modification method are urgent and undeveloped areas of research. It is difficult to directly integrate organoboronic acids within inorganic borate chemistry by adopting the traditional preparation approaches. This work reports a facile synthetic method to synthesize a large family of pyrazole molecule-protected borates in a rapid and precise manner under mild conditions. A unique cyclic eight-membered B4O4-ring has been identified as the cluster core for all these hybrid borates with two different conformations (boat and crown). This strategy can be applied to a system of pyrazolyl molecules to generate such hybrid borates in two independent routes from organoboronic or inorganic boric acids. Furtherly, the mechanism of 'click reaction' between boric acid and pyrazole induced by copper ions has been proposed based on the synthetic conditions and the structure of intermediate. Due to the bimetallic Cu sites and the functional surfaces, these materials can be used as electrocatalysts for CO2 reduction reaction and efficiently enhance the selectivity of HCOOH and C2H4. Our strategy can be regarded as a typical template technique for organic molecule-protected borates.

Health economic evaluation of an artificial intelligence (AI)-based rapid nutritional diagnostic system for hospitalised patients: A multicentre, randomised controlled trial.

BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).

Effect of "He Tiao Du Ren An Shen Acupuncture" on restless leg syndrome: A randomized trial.

BACKGROUND: This study aimed to observe the clinical effects of "He Tiao Du Ren An Shen Acupuncture" (HTDRAS Acupuncture) for treating restless leg syndrome (RLS). METHODS: We randomly divided 66 RLS patients into 2 groups: the observation group received "He Tiao Du Ren An Shen Acupuncture" and the control group received conventional acupuncture. All participants were treated once a day, 6 days a week, with 1 day off, for a total of 1 month. Clinical effectiveness of the 2 groups was compared, neurotransmitter levels, the International Restless Leg Syndrome Scale and the Hamilton Anxiety Scale were assessed in both groups. RESULTS: The curative effect in the observation group was better than that in the control group (P < .05). After treatment, the expression of 5-hydroxytryptamine in the observation group was higher than in the control group (P < .05). The International Restless Leg Syndrome Scale and Hamilton Anxiety Scale scores in observation group were lower than those in control group (P < .05). CONCLUSION: "He Tiao Du Ren An Shen Acupuncture" for RLS is significantly effective and safe. It can effectively improve the levels of 5-hydroxytryptamine in RLS patients, alleviate clinical symptoms and reduce anxiety. This treatment has a high clinical application value and is worthy of clinical promotion.

PEG-SeNPs as therapeutic agents inhibiting apoptosis and inflammation of cells infected with H1N1 influenza A virus.

The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1ß, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

miRNA and mRNA Signatures in Human Acute Kidney Injury Tissue.

Acute kidney injury (AKI) is an important contributor to the development of chronic kidney disease (CKD). There is a need to understand molecular mediators that drive recovery and progression to CKD. In particular, the regulatory role of miRNAs in AKI is poorly understood. miRNA and mRNA sequencing were performed on biobanked human kidney tissues obtained in the routine care of subjects with a diagnosis of AKI, minimal change disease (MCD), or without known kidney disease in nephrectomy (Ref) tissue. mRNA analysis revealed that Ref tissues exhibited an injury signature similar to AKI, and not identified in MCD samples. The transcriptomic signature of human AKI was enriched in pathways involved in cell adhesion, epithelial-to-mesenchymal transition, and cell cycle arrest (e.g., CDH6, ITGB6, CDKN1A). In AKI, upregulation of miR-146a, miR-155, miR-142, miR-122 was associated with pathways involved in immune cell recruitment, inflammation, and epithelial-to-mesenchymal transition. miR-122 and miR-146 are associated with downregulation of DDR2 and IGFBP6, genes involved in recovery and progression of kidney disease. These data provide integrated miRNA signatures that complement mRNA and other epigenetic data available in kidney atlases.

Aboveground biomass stocks of species-rich natural forests in southern China are influenced by stand structural attributes, species richness and precipitation.

Forests, the largest terrestrial carbon sinks, play an important role in carbon sequestration and climate change mitigation. Although forest attributes and environmental factors have been shown to impact aboveground biomass, their influence on biomass stocks in species-rich forests in southern China, a biodiversity hotspot, has rarely been investigated. In this study, we characterized the effects of environmental factors, forest structure, and species diversity on aboveground biomass stocks of 30 plots (1 ha each) in natural forests located within seven nature reserves distributed across subtropical and marginal tropical zones in Guangxi, China. Our results indicate that forest aboveground biomass stocks in this region are lower than those in mature tropical and subtropical forests in other regions. Furthermore, we found that aboveground biomass was positively correlated with stand age, mean annual precipitation, elevation, structural attributes and species richness, although not with species evenness. When we compared stands with the same basal area, we found that aboveground biomass stock was higher in communities with a higher coefficient of variation of diameter at breast height. These findings highlight the importance of maintaining forest structural diversity and species richness to promote aboveground biomass accumulation and reveal the potential impacts of precipitation changes resulting from climate warming on the ecosystem services of subtropical and northern tropical forests in China. Notably, many natural forests in southern China are not fully stocked. Therefore, their continued growth will increase their carbon storage over time.

Adaptability to the environment of protease by secondary structure changes and application to enzyme-selective hydrolysis.

The reactions involving enzymes are significantly influenced by various environmental factors. Clarity of how the activity and structure of proteases impact their function is crucial for more efficient application of enzymes as a tool. The impact of temperature, pH, and ionic strength on changes in protease activity, secondary structure, and protein conformation during enzymatic hydrolysis were investigated in this study. The enzymatic activity and secondary structure of acid-base protease were found to undergo significant modifications under different physical conditions, as demonstrated by UV spectrophotometry and FTIR spectroscopy analysis. Specifically, variations in α-helix and ß-fold content were observed to correlate with changes in enzyme activity. Molecular simulation analysis revealed that physical conditions have varying effects on the protease, particularly influencing enzyme activity and secondary structure. Evaluation of the proteases indicated alterations in both enzyme activity and structure. This treatment selectively hydrolyzed ß-lactoglobulin and reduced sensitization. These findings offer novel perspectives on the functionalities and regulatory mechanisms of proteases, as well as potential industrial applications.

Rapid and accurate quantification of trypsin activity using integrated infrared and ultraviolet spectroscopy with data fusion techniques.

Proteases play a crucial role in industrial enzyme formulations, with activity fluctuations significantly impacting product quality and yield. Therefore, developing a method for precise and rapid detection of protease activity is paramount. This study aimed to develop a rapid and accurate method for quantifying trypsin activity using integrated infrared (IR) and ultraviolet (UV) spectroscopy combined with data fusion techniques. The developed method evaluates the enzymatic activity of trypsin under varying conditions, including temperature, pH, and ionic strength. By comparing different data fusion methods, the study identifies the optimal model for accurate enzyme activity prediction. The results demonstrated significant improvements in predictive performance using the feature-level data fusion approach. Additionally, substituting the spectral data of the samples in the validation sets into the best prediction model resulted in a minimal residual difference between predicted and true values, further verifying the model's accuracy and reliability. This innovative approach offers a practical solution for the efficient and precise quantification of enzyme activity, with broad applications in industrial processes.

Exploratory analysis of high-dose corticosteroid therapy on epileptic encephalopathy with spike-and-wave activation in sleep.

Objective: This study aims to evaluate the therapeutic efficacy of high-dose corticosteroid therapy in children diagnosed with epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS), investigate associated clinical indicators influencing treatment outcomes, and establish a predictive model for recurrence. Methods: Children diagnosed with EE-SWAS who received high-dose corticosteroid therapy were categorized into responder group and non-responder group. Data on clinical parameters, electroencephalogram (EEG) features, and serum cytokine levels were collected. Six months post-treatment, the effectively treated children were further stratified into recurrence and non-recurrence groups. Risk factors for poor outcomes following corticosteroid therapy were identified using univariate analysis. Multivariate logistic regression analysis was then employed to determine independent factors influencing the recurrence of corticosteroid therapy, which facilitated the development of a predictive model. Results: The study included 48 children, with 33 cases in the responder group (effective rate = 68.8%) and 15 cases in the non-responder group. The responder group exhibited an older onset age of electrical status epilepticus in sleep (ESES) and higher proportions of combined benzodiazepines (BZDs) use (P < 0.05). Among those responding to corticosteroid therapy, 11 cases experienced a recurrence (recurrence rate = 33.3%), while 22 cases did not. Significant differences were observed between the two groups concerning age of seizure onset, age of ESES onset, seizure frequency, atypical presentations, and concomitant frontal lobe discharges (all P < 0.05). Concomitant frontal lobe discharges and an earlier age of seizure onset were identified as risk factors for ESES recurrence following corticosteroid therapy. The predictive model was formulated as Logit(P) = 2.35 × presence of frontal lobe discharges-0.802 × age of seizure onset + 2.457. The Area Under the Curve (AUC) of Receiver Operating Characteristics (ROC) was 0.93, with sensitivity and specificity at 100% and 77.3%, respectively. Conclusion: High-dose corticosteroid therapy for EE-SWAS exhibited a high effective rate as well as a notable recurrence rate. Onset age of ESES and combined benzodiazepines usage correlated with therapeutic efficacy. Seizure onset age and the presence of frontal lobe discharges may hold predictive value for recurrence following corticosteroid therapy.

Terahertz polarization conversion and asymmetric transmission based on a liquid crystal integrated EIT metasurface.

We experimentally demonstrate a liquid crystal (LC)-integrated EIT metasurface for active THz polarization conversion and asymmetric transmission. By controlling the LC orientation under static magnetic field anchoring and an adjustable electric field, the device realizes the active control from the OFF state to the ON state, corresponding to the orthogonal polarization excitation modes of the EIT metasurface. Furthermore, based on the different polarization responses at forward and backward incidences, we achieve asymmetric transmission at the EIT peak and two nearby resonances, with its isolation actively manipulated by the external electric field. This study on dynamic polarization conversion and asymmetric transmission by a LC-integrated metasurface offers a promising route for active THz devices, applicable to THz communication, switching, and sensing systems.

Clinically significant changes in anal sphincter hiatal area in patients with gestational diabetes mellitus and pelvic organ prolapse.

BACKGROUND: The prevalence of pelvic organ prolapse (POP) increases with age and parity. Specifically, the prevalence of POP among women aged 20 to 39 is 9.7%, while it rises to 49% among women over 80 years old. Additionally, as the number of deliveries increases, the prevalence of POP also rises accordingly, with a rate of 12.8% for women with one delivery history, 18.7% for those with two deliveries, and 24.6% for women with three or more deliveries. It causes immense suffering for pregnant women. AIM: To evaluate the relationship between the levator ani muscle's hiatus (LH) area and POP in patients with gestational diabetes mellitus (GDM) using perineal ultra-sound. METHODS: The study cohort comprised 104 patients aged 29.8 ± 3.7 years who sought medical care at our institution between January 2021 and June 2023. All were singleton pregnancies consisting of 75 primiparas and 29 multiparas, with an average parity of 1.7 ± 0.5. According to the POP diagnostic criteria, the 104 subjects were divided into two groups with 52 members each: POP group (patients with GDM combined with POP) and non-POP group (patients with GDM without POP). Perineal ultrasound was used to measure differences in the anteroposterior diameter, transverse diameter, and LH area. Receiver operating characteristic curves were drawn to determine the optimal cutoff values for the LH anteroposterior diameter, transverse diameter, and area for diagnosing POP. RESULTS: Statistically significant increase in the LH area, anteroposterior diameter, and lateral diameter were observed in the POP group compared with the non-POP group (P < 0.05). Both groups exhibited markedly elevated incidence rates of macrosomia and stress urinary incontinence. For the POP group, the area under the curve (AUC) for the LH area was 0.906 with a 95% confidence interval (CI): 0.824-0.988. The optimal cutoff was 13.54cm², demonstrating a sensitivity of 83.2% and a specificity of 64.4%. The AUC for the anteroposterior diameter reached 0.836 with a 95%CI: 0.729-0.943. The optimal cutoff was 5.53 cm with a sensitivity of 64.2% and a specificity of 73.4%. For the lateral diameter, its AUC was 0.568 with a 95%CI: 0.407-0.729. The optimal cutoff was 4.67 cm, displaying a sensitivity of 65.9% and a specificity of 69.3%. Logistic regression analysis unveiled that age, body weight, number of childbirths, total number of pregnancies, and gestational weight gain constituted the independent risk factors for the cooccurrence of GDM and POP. CONCLUSION: Three-dimensional perineal ultrasonography of LH size and shape changes can effectively diagnose POP. Age, weight, number of births, number of pregnancies, and weight gain during pregnancy are independent risk factors affecting the cooccurrence of GDM and POP. GDM can increase the LH area in patients, and an enlarged LH leads to an increased incidence of POP.

Therapeutic drug monitoring of free perampanel concentrations in practice: A practical analytical technique based on centrifugal ultrafiltration sample separation.

Objectives: The centrifugal ultrafiltration-high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to determine the free perampanel (PER) concentration in children with epilepsy. Methods: Free PER concentration was obtained using centrifugal ultrafiltration devices. The internal standard was PER-D5. The method was investigated for selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, matrix effects, recovery, and stability. The Spearman's correlation coefficient was used to evaluate the correlation between the free and total PER concentrations. A nonparametric test was used to estimate the effects of PER along with other antiepileptic drugs on the total and free PER concentrations. Results: The free PER concentration was positively correlated with the total PER concentration in the 57 plasma samples (r = 0.793 > 0, P < 0.001). Additionally, the free PER concentrations were significantly (P < 0.05) increased in valproic acid (VPA) co-therapy (9.87 ± 5.83) compared with non-VPA co-therapy (5.03 ± 4.57). Conclusions: The proposed method is efficient, sensitive, and suitable for detecting free PER concentrations in children with epilepsy. Simultaneously, the free PER concentration response to clinical outcomes in children with epilepsy was more clinically significant, particularly when combined with VPA.

FUSION: A web-based application for in-depth exploration of multi-omics data with brightfield histology.

Spatial -OMICS technologies facilitate the interrogation of molecular profiles in the context of the underlying histopathology and tissue microenvironment. Paired analysis of histopathology and molecular data can provide pathologists with otherwise unobtainable insights into biological mechanisms. To connect the disparate molecular and histopathologic features into a single workspace, we developed FUSION (Functional Unit State IdentificatiON in WSIs [Whole Slide Images]), a web-based tool that provides users with a broad array of visualization and analytical tools including deep learning-based algorithms for in-depth interrogation of spatial -OMICS datasets and their associated high-resolution histology images. FUSION enables end-to-end analysis of functional tissue units (FTUs), automatically aggregating underlying molecular data to provide a histopathology-based medium for analyzing healthy and altered cell states and driving new discoveries using "pathomic" features. We demonstrate FUSION using 10x Visium spatial transcriptomics (ST) data from both formalin-fixed paraffin embedded (FFPE) and frozen prepared datasets consisting of healthy and diseased tissue. Through several use-cases, we demonstrate how users can identify spatial linkages between quantitative pathomics, qualitative image characteristics, and spatial --omics.

Differential Back Muscle Flexion-Relaxation Phenomenon in Constrained versus Unconstrained Leg Postures.

Previous studies examining the flexion-relaxation phenomenon (FRP) in back muscles through trunk forward flexion tests have yielded inconsistent findings, primarily due to variations in leg posture control. This study aimed to explore the influence of leg posture control and individual flexibility on FRP in back and low limb muscles. Thirty-two male participants, evenly distributed into high- and low-flexibility groups, were recruited. Activities of the erector spinae, biceps femoris, and gastrocnemius muscles, alongside the lumbosacral angle (LSA), were recorded as participants executed trunk flexion from 0° to 90° in 15° increments, enabling an analysis of FRP and its correlation with the investigated variables. The findings highlighted significant effects of all examined factors on the measured responses. At a trunk flexion angle of 60°, the influence of leg posture and flexibility on erector spinae activities was particularly pronounced. Participants with limited flexibility exhibited the most prominent FRP under constrained leg posture, while those with greater flexibility and unconstrained leg posture displayed the least FRP, indicated by their relatively larger LSAs. Under constrained leg posture conditions, participants experienced an approximate 1/3 to 1/2 increase in gastrocnemius activity throughout trunk flexion from 30° to 90°, while biceps femoris activity remained relatively constant. Using an inappropriate leg posture during back muscle FRP assessments can overestimate FRP. These findings offer guidance for designing future FRP research protocols.

From Feeling Tough to Mental Growth: Coping with Sexual Bullying During Childhood in Gay and Bisexual Men.

This qualitative study was conducted to understand how gay and bisexual men (GBM) in Taiwan cope with childhood bullying because of their sexual orientation or gender nonconformity. We explored their journey from feeling disturbed to receiving social support, developing coping strategies, and achieving self-growth. Colaizzi's phenomenological approach was used to investigate subject experiences. Semi-structured interviews were conducted with 21 GBM who had experienced high-level sexual bullying in childhood. Relevant data were collected to assess their experiences of sexual bullying, their coping strategies, and subjective effects of corresponding adjustments in interpersonal interactions. Subject experiences concentrated on six themes related to sexual bullying and coping strategies: bullying at developmental stages, bullying everywhere, facing bullying alone, various impacts of bullying, overcoming challenges of interpersonal relationships, and building a strong and carefree self. Our findings can provide mental health professionals with key insights into the contexts of sexual bullying and the associated psychological distress in GBM. This study further clarifies the coping responses of these individuals and their psychological growth following such adverse experiences.

A Coupling-Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells.

The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.