Efficacy and safety of endoscopic nasobiliary drainage versus percutaneous transhepatic cholangial drainage in the treatment of advanced hilar cholangiocarcinoma: a systematic review and meta-analysis.

OBJECTIVE: To evaluate and compare the efficacy and safety of Endoscopic Nasobiliary Drainage (ENBD) and Percutaneous Transhepatic Cholangiography Drainage (PTCD) in patients with advanced Hilar Cholangiocarcinoma (HCCA) through a meta-analysis of clinical studies. METHODS: We searched Chinese and English databases, including China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Embase, Scopus, and Web of Science, for relevant literatures on PTCD and ENBD for advanced HCCA clinical trials. Two investigators independently screened the literatures, and the quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). The primary endpoint was the success rate of biliary drainage operation, while secondary endpoints included Total Bilirubin (TBIL) change, acute pancreatitis, biliary tract infection, hemobilia, and other complications. R software was used for data analysis. RESULTS: A comprehensive database search, based on predefined inclusion and exclusion criteria, yielded 26 articles for this study. Analysis revealed that PTCD had a significantly higher success rate than ENBD [OR (95% CI) = 2.63 (1.98, 3.49), Z=6.70, P<0.05]. PTCD was also more effective in reducing TBIL levels post-drainage [SMD (95%CI) =-0.13 (-0.23, -0.03), Z=-2.61, P<0.05]. While ENBD demonstrated a lower overall complication rate [OR (95%CI) = 0.60 (0.43, 0.84), Z=-2.99, P<0.05], it was associated with a significantly lower incidence of post-drainage biliary hemorrhage compared to PTCD [OR=3.02, 95%CI: (1.94-4.71), Z= 4.89, P<0.01]. CONCLUSIONS: This meta-analysis compares the efficacy and safety of ENBD and PTCD for palliative treatment of advanced HCCA. While both are effective, PTCD showed superiority in achieving successful drainage, reducing TBIL, and lowering the incidence of acute pancreatitis and biliary infections. However, ENBD had a lower risk of post-drainage bleeding. Clinicians should weigh these risks and benefits when choosing between ENBD and PTCD for individual patients. Further research is needed to confirm these findings and explore long-term outcomes.

Effects of Minor Zn Dopants in Sn-10Bi Solder on Interfacial Reaction and Shear Properties of Solder on Ni/Au Surface Finish.

Sn-10Bi low-bismuth-content solder alloy provides a potential alternative to the currently used Sn-Ag-Cu series due to its lower cost, excellent ductility, and strengthening resulting from the Bi solid solution and precipitation. This study primarily investigates the interfacial evolution and shear strength characteristics of Sn-10Bi joints on a Ni/Au surface finish during the as-soldered and subsequent isothermal aging processes. To improve the joint performance, a 0.2 or 0.5 wt.% dopant of Zn was incorporated into Sn-10Bi solder. The findings demonstrated that a 0.2 or 0.5 wt.% Zn dopant altered the composition of the intermetallic compound (IMC) formed at the interface between the solder and Ni/Au surface finish from Ni3Sn4 to Ni3(Sn, Zn)4. The occurrence of this transformation is attributed to the diffusion of Zn atoms into the Ni3Sn4 lattice, resulting in the substitution of a portion of the Sn atoms by Zn atoms, thereby forming the Ni3(Sn, Zn)4 IMC during the soldering process, which was also verified by calculations based on first principles. Furthermore, a 0.2 or 0.5 wt.% Zn dopant in Sn-10Bi significantly inhibited the Ni3(Sn, Zn)4 growth after both the soldering and thermal aging processes. Zn addition can enhance the shear strength of solder joints irrespective of the as-soldered or aging condition. The fracture mode was determined by the aging durations-with the brittle mode occurring for as-soldered joints, the ductile mode occurring for aged joints after 10 days, and again the brittle mode for joints after 40 days of aging.

The Flavonoid Glycoside from Abrus cantoniensis Hance Alleviates Alcoholic Liver Injury by Inhibiting Ferroptosis in an AMPK-Dependent Manner.

Abrus cantoniensis Hance is a vegetative food and can be used as a folk beverage or soup to clear liver toxins and prevent liver damage. However, the components and effects of A. cantoniensis Hance in alcohol-induced liver injury were unknown. This study aimed to obtain abundant phytochemicals from A. cantoniensis Hance and identify the potency of the isolates in preventing alcohol-induced liver injury. Alcohol-stimulated AML12 cells and Lieber-DeCarli diet-fed mice were used to establish in vitro and in vivo models, respectively. Our findings indicated that flavonoid glycosides, especially AH-15, could significantly alleviate alcohol-induced liver injury by inhibiting oxidative stress. Furthermore, we demonstrated that AH-15 inhibited ferroptosis induced by lipid peroxidation. Mechanically, we found that AH-15 regulated nuclear factor erythroid 2-related factor 2 (NRF2) expression via activation of AMP-activated protein kinase (AMPK) signaling. These results indicate that A. cantoniensis Hance is a great potential functional food for alleviating alcohol-induced liver injury.

The Impact of Birth Season and Sex on Motor Skills in 2-Year-Old Children: A Study in Jinhua, Eastern China.

BACKGROUND: This study investigates the effects of birth season and sex on the development of gross and fine motor skills in 2-year-old children in Jinhua, Eastern China. METHODS: Conducted in Jinhua, a city in central Zhejiang Province, Eastern China, this research involved 225 children, assessing their gross and fine motor skills using the Peabody Developmental Motor Scales, Second Edition. Scores were adjusted for age in months to avoid the relative age effect. Statistical analyses included MANOVA to evaluate the impacts of season and sex. RESULTS: Sex had no significant impact on overall motor development scores (p > 0.05). However, the season of birth significantly affected fine motor quotient (FMQ) and total motor quotient (TMQ) (p < 0.05). Boys' motor skills were generally unaffected by season, whereas girls born in winter exhibited superior fine motor skills compared to those born in summer. CONCLUSIONS: Seasonal environmental factors significantly influence early motor development, particularly fine motor skills in girls. These findings highlight the importance of considering seasonal variations in early childhood interventions aimed at enhancing exercise physiology and sports performance.

Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy.

The utilization of PD-1/PD-L1 inhibitors marks a significant advancement in cancer therapy. However, the efficacy of monotherapy is still disappointing in a substantial subset of patients, necessitating the exploration of combinational strategies. Emerging from the promising results of the KEYNOTE-942 trial, RNA-based therapies, particularly circRNAs and piRNAs, have distinguished themselves as innovative sensitizers to immune checkpoint inhibitors (ICIs). These non-coding RNAs, notable for their stability and specificity, were once underrecognized but are now known for their crucial roles in regulating PD-L1 expression and bolstering anti-cancer immunity. Our manuscript offers a comprehensive analysis of selected circRNAs and piRNAs, elucidating their immunomodulatory effects and mechanisms, thus underscoring their potential as ICIs enhancers. In conjunction with the recent Nobel Prize-awarded advancements in mRNA vaccine technology, our review highlights the transformative implications of these findings for cancer treatment. We also discuss the prospects of circRNAs and piRNAs in future therapeutic applications and research. This study pioneers the synergistic application of circRNAs and piRNAs as novel sensitizers to augment PD-1/PD-L1 inhibition therapy, demonstrating their unique roles in regulating PD-L1 expression and modulating immune responses. Our findings offer a groundbreaking approach for enhancing the efficacy of cancer immunotherapy, opening new avenues for treatment strategies. This abstract aims to encapsulate the essence of our research and the burgeoning role of these non-coding RNAs in enhancing PD-1/PD-L1 inhibition therapy, encouraging further investigation into this promising field.

Chinese Herbal Medicine Combined With Liuzijue Exercise in Physiological Rehabilitation After Video-assisted Lung Lobectomy for Cancer: A Prospective Propensity Score Matching Study.

OBJECTIVE: To observe the clinical efficacy of Chinese herbal medicine combined with Liuzijue exercise on the physiological symptoms and quality of life (QoL) in postoperative patients with early-stage lung cancer. METHODS: One hundred and eighty-three lung cancer patients who underwent video-assisted thoracoscopic surgery (VATS) were categorize into either a traditional Chinese medicine treatment group (CM) or a control group (non-traditional Chinese medicine treatment, NC), among whom 73 underwent Chinese herbal medicine and Liuzijue therapy, while 110 underwent no comprehensive treatment with traditional Chinese medicine. The propensity score matching (PSM) method with a 1:2 ratio was used to balance the baseline characteristics and evaluate the efficacy of CM in improving postoperative symptoms and QoL. RESULTS: Cough, dyspnea, chest pain, and fatigue were the most common clinical symptoms after VATS. Except for chest pain, they were all correlated with the scope of operation (P < .05). After PSM, 165 patients were identified in the matched cohort, and the covariates of gender, age, operative site, and scope of operation were balanced between the 2 groups (P > .05). In the domain of global health status, the improvement in QoL in CM was greater than that in NC (6.06 ± 15.83 vs -1.06 ± 14.68, P = .005). In terms of symptoms, improvements in cough (1.69 ± 3.15 vs 0.38 ± 2.63, P = .006), dyspnea during climbing stairs (-10.30 ± 16.82 vs -1.82 ± 17.97, P = .004), and pain (-0.76 ± 1.32 vs -0.08 ± 1.31, P = .002) in CM were better than in NC. CONCLUSION: Comprehensive treatment with traditional Chinese medicine (TCM) can provide therapeutic benefits in physiological rehabilitation after VATS for cancer.

Novel drug-drug salt crystals of metformin with ibuprofen or naproxen: Improved solubility, dissolution rate, and synergistic antinociceptive effects.

As the monotherapy of available analgesics is usually accompanied by serious side effects or limited efficacy in the management of chronic pain, multimodal analgesia is widely used to achieve improved benefit-to-risk ratios in clinic. Drug-drug salts are extensively researched to optimize the physicochemical properties of active pharmaceutical ingredients (APIs) and achieve clinical benefits compared with individual APIs or their combination. New drug-drug salt crystals metformin-ibuprofen (MET-IBU) and metformin-naproxen (MET-NAP) were prepared from metformin (MET) and two poorly water-soluble anti-inflammatory drugs (IBU and NAP) by the solvent evaporation method. The structures of these crystals were confirmed by single crystal and powder X-ray diffraction, Hirshfeld surface, Fourier transform infrared spectroscopy and thermal analysis. Both MET-IBU and MET-NAP showed significantly improved solubility and intrinsic dissolution rate than the pure IBU or NAP. The stability test indicated that MET-IBU and MET-NAP have excellent physical stability under stressing test (10 days) and accelerated conditions (3 months). Moreover, isobolographic analysis suggested that MET-IBU and MET-NAP exerted potent and synergistic antinociceptive effects in λ-Carrageenan-induced inflammatory pain in mice, and both of them had an advantage in rapid pain relief. These results demonstrated the potential of MET-IBU and MET-NAP to achieve synergistic antinociceptive effects by developing drug-drug salt crystals.

Polygenic adaptation of a cosmopolitan pest to a novel thermal environment.

The fluctuation in temperature poses a significant challenge for poikilothermic organisms, notably insects, particularly in the context of changing climatic conditions. In insects, temperature adaptation has been driven by polygenes. In addition to genes that directly affect traits (core genes), other genes (peripheral genes) may also play a role in insect temperature adaptation. This study focuses on two peripheral genes, the GRIP and coiled-coil domain containing 2 (GCC2) and karyopherin subunit beta 1 (KPNB1). These genes are differentially expressed at different temperatures in the cosmopolitan pest, Plutella xylostella. GCC2 and KPNB1 in P. xylostella were cloned, and their relative expression patterns were identified. Reduced capacity for thermal adaptation (development, reproduction and response to temperature extremes) in the GCC2-deficient and KPNB1-deficient P. xylostella strains, which were constructed by CRISPR/Cas9 technique. Deletion of the PxGCC2 or PxKPNB1 genes in P. xylostella also had a differential effect on gene expression for many traits including stress resistance, resistance to pesticides, involved in immunity, trehalose metabolism, fatty acid metabolism and so forth. The ability of the moth to adapt to temperature via different pathways is likely to be key to its ability to remain an important pest species under predicted climate change conditions.

Flexible-Arranged Biomimetic Array Integrated with Parallel Entropy-Driven Circuits for Ultrasensitive, Multiple, and Reliable Detection of Cancer-Related MicroRNAs.

With the emergence of microRNA (miRNA) as a promising biomarker in cancer diagnosis, it is significant to develop multiple analyses of miRNAs. However, it still faces difficulties in ensuring the sensitivity and accuracy during multiplex detection owing to the low abundance and experimental deviation of miRNAs. In this work, a flexible-arranged biomimetic array integrated with parallel entropy-driven circuits (EDCs) was developed for ultrasensitive, multiplex, reliable, and high-throughput detection of miRNAs. The biomimetic array was fabricated by arrangement of various photonic crystals (PCs) for adjustable photonic band gaps (PBGs) and specific fluorescence enhancement. Meanwhile, two cancer-related miRNAs and one reference miRNA were introduced as multiple analytes as a proof-of-concept. The parallel EDCs with negligible crosstalk were designed based on the modular property. Because of the one-to-one match between the emitted fluorescence of parallel EDCs and the PBGs of the flexible-arranged biomimetic array, the generated fluorescence signal triggered by target miRNAs can be enhanced on the corresponding domain of the array. Furthermore, the amplified signal of the array was detected with high-throughput scanning, which could reveal specific information on cancer-related miRNAs as well as reference miRNA, enhancing the abundance and reliability of the analysis. The proposed array has the merits of a modular design, flexible deployment, simple operation (nonenzymatic and isothermal), improved accuracy, high sensitivity, and multiplex analysis, showing potential in disease diagnosis.

Thermal acclimation uncovers a simple genetic basis of adaptation to high temperature in a cosmopolitan pest.

Understanding a population's fitness heterogeneity and genetic basis of thermal adaptation is essential for predicting the responses to global warming. We examined the thermotolerance and genetic adaptation of Plutella xylostella to exposure to hot temperatures. The population fitness parameters of the hot-acclimated DBM strains varied in the thermal environments. Using genome scanning and transcription profiling, we find a number of genes potentially involved in thermal adaptation of DBM. Editing two ABCG transporter genes, PxWhite and PxABCG, confirmed their role in altering cuticle permeability and influencing thermal responses. Our results demonstrate that SNP mutations in genes and changes in gene expression can allow DBM to rapidly adapt to thermal environment. ABCG transporter genes play an important role in thermal adaptation of DBM. This work improves our understanding of genetic adaptation mechanisms of insects to thermal stress and our capacity to predict the effects of rising global temperatures on ectotherms.

PROTAC Prodrug-Integrated Nanosensitizer for Potentiating Radiation Therapy of Cancer.

Radiation therapy (RT) is one of the primary options for clinical cancer therapy, in particular advanced head and neck squamous cell carcinoma (HNSCC). Herein, the crucial role of bromodomain-containing protein 4 (BRD4)-RAD51 associated protein 1 (RAD51AP1) axis in sensitizing RT of HNSCC is revealed. A versatile nanosensitizer (RPB7H) is thus innovatively engineered by integrating a PROteolysis TArgeting Chimeras (PROTAC) prodrug (BPA771) and hafnium dioxide (HfO2) nanoparticles to downregulate BRD4-RAD51AP1 pathway and sensitize HNSCC tumor to RT. Upon intravenous administration, the RPB7H nanoparticles selectively accumulate at the tumor tissue and internalize into tumor cells by recognizing neuropilin-1 overexpressed in the tumor mass. HfO2 nanoparticles enhance RT effectiveness by amplifying X-ray deposition, intensifying DNA damage, and boosting oxidative stress. Meanwhile, BPA771 can be activated by RT-induced H2O2 secretion to degrade BRD4 and inactivate RAD51AP1, thus impeding RT-induced DNA damage repair. This versatile nanosensitizer, combined with X-ray irradiation, effectively regresses HNSCC tumor growth in a mouse model. The findings introduce a PROTAC prodrug-based radiosensitization strategy by targeting the BRD4-RAD51AP1 axis, may offer a promising avenue to augment RT and more effective HNSCC therapy.

Altered spontaneous brain activity in lumbar disc herniation patients: insights from an ALE meta-analysis of neuroimaging data.

Objective: To explore the characteristics of spontaneous brain activity changes in patients with lumbar disc herniation (LDH), and help reconcile the contradictory findings in the literature and enhance the understanding of LDH-related pain. Materials and methods: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), SinoMed, and Wanfang databases were searched for literature that studies the changes of brain basal activity in patients with LDH using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation/fraction amplitude of low-frequency fluctuation (ALFF/fALFF) analysis methods. Activation likelihood estimation (ALE) was used to perform a meta-analysis of the brain regions with spontaneous brain activity changes in LDH patients compared with healthy controls (HCs). Results: A total of 11 studies were included, including 7ALFF, 2fALFF, and 2ReHo studies, with a total of 269 LDH patients and 277 HCs. Combined with the data from the ALFF/fALFF and ReHo studies, the meta-analysis results showed that compared with HCs, LDH patients had increased spontaneous brain activity in the right middle frontal gyrus (MFG), left anterior cingulate cortex (ACC) and the right anterior lobe of the cerebellum, while they had decreased spontaneous brain activity in the left superior frontal gyrus (SFG). Meta-analysis using ALFF/fALFF data alone showed that compared with HCs, LDH patients had increased spontaneous brain activity in the right MFG and left ACC, but no decrease in spontaneous brain activity was found. Conclusion: In this paper, through the ALE Meta-analysis method, based on the data of reported rs-fMRI whole brain studies, we found that LDH patients had spontaneous brain activity changes in the right middle frontal gyrus, left anterior cingulate gyrus, right anterior cerebellar lobe and left superior frontal gyrus. However, it is still difficult to assess whether these results are specific and unique to patients with LDH. Further neuroimaging studies are needed to compare the effects of LDH and other chronic pain diseases on the spontaneous brain activity of patients. Furthermore, the lateralization results presented in our study also require further LDH-related pain side-specific grouping study to clarify this causation. Systematic review registration: PROSPERO, identifier CRD42022375513.

Why is Smartphone Addiction More Common in Adolescents with Harsh Parenting? Depression and Experiential Avoidance's Multiple Mediating Roles.

Purpose: Harsh parenting is positively correlated with adolescents' smartphone addiction, according to a growing corpus of studies. The various mediating processes that could underlie this link, however, are not well understood. Based upon the experiential avoidance model, the current research aimed to identify the relation between harsh parenting and adolescents' smartphone addiction and the mediating roles of adolescents' depression and experiential avoidance. Methods: We recruited 456 adolescents (female = 52.6%; Mage = 13.19 years, SD = 0.85) at a public junior high school in China to complete the harsh discipline scale, 90-item Hopkins symptom checklist, acceptance and action questionnaire version II, and smartphone addiction scale short version. SPSS24.0 was used to conduct independent samples t-test, descriptive statistics, Pearson correlation analysis and common method bias test, PROCESS were used to conduct a significance test of the chain mediation effect on the data. Age, gender, and grade were used as con-founders that were controlled in order to make cautious predictions. Results: The results showed that (1) harsh parenting was positively correlated with adolescents' depression, experiential avoidance, and smartphone addiction; (2) both depression and experiential avoidance fully mediated the link between harsh parenting and smartphone addiction; and (3) depression and experiential avoidance also sequentially mediated the link between harsh parenting and smartphone addiction. These findings have significant implications for the prevention and intervention of adolescents' smartphone addiction. Conclusion: These findings suggested that harsh parenting may have an indirect impact on smartphone addiction in both a simple way (parallel mediation) and a complicated way (serial mediation). In addition, these studies shed light on smartphone addiction prevention and intervention.

Influence of different caregiving styles on fundamental movement skills among children.

Purpose: This study investigated the influence of parenting and grandparenting caregiving styles on fundamental motor skills (FMS) of preschool children. Method: A total of 1,326 preschool children (698 boys, 628 girls) aged 4-6 years were recruited from the kindergartens of Jinhua City, China. Locomotor skills (LM), ball skills (BS), and total fundamental movement skills (TS) of children were assessed by the Test of Gross Motor Development-3rd edition (TGMD-3). Results: There were 978 children in parenting and 348 children in grandparenting caregiving styles. The LM, BS and TS scores of children were considerably (p < 0.001) increased with age (irrespective of sex or caregiving style). For the sex comparisons, BS scores of boys were significantly higher than girls (p < 0.001), while LM and TS scores were not different between boys and girls. For the caregiving style comparison, parenting is superior to grandparenting in developing of children's FMS. Parenting boys of 4-, 5-, and 6-years old showed better BS compared to age-matched parenting girls, whereas boys of 5-years old in grandparenting only showed better BS compared to same-age grandparenting girls (p < 0.05). Furthermore, parenting boys of 6-years reported higher LM (p < 0.01), BS (p < 0.001), and TS (p < 0.001) scores compared to grandparenting boys, but girls' FMS at all ages were not significantly different between the caregiving styles. Conclusion: Parenting caregiving style is positively associated with proper development of FMS among children. Girl children with poor FMS in grandparenting may need a special care or intervention programs to promote their FMS.

Spatial-temporal evolution of soil gas Rn before two Ms ≥ 5.0 earthquakes in the mid-eastern of the Qilian fault zone (QLF).

The mid-eastern segment of the Qilianshan fault zone (QLF) on the northeastern margin of the Qinghai-Tibet Plateau is considered one of the key seismic hazard areas. The Zhangye Ms5.0 earthquake and Menyuan Ms6.9 earthquake are the two Ms ≥ 5.0 earthquakes in recent years. The spatio-temporal evolution of Rn across the fault before the two Ms ≥ 5.0 earthquakes were explored by combining a solid seismogenic model and numerical simulation results in this study. The results demonstrates the spatial distribution of Rn concentration intensity varies over time, indicating the evolving characteristics of fracture zone activity. The time-series variation characteristics are closely related the Zhangye Ms5.0 earthquake and Menyuan Ms6.9 earthquake. Overall, in the seismic source area and surrounding medium area of Zhangye Ms5.0 earthquake, the soil gas Rn anomaly across faults characterized by a turning upward trend after continuous decline. The closer to the source area, the more obvious the upward trend. For Menyuan Ms6.9 earthquake, the survey line (HT1) located in the main fracture zone of the earthquake and the survey line (HT7,30km from the epicenter) closer to the epicenter also showed a similar trend, while the other measurement lines in far-field exhibit declining trend before the Menyuan Ms6.9 earthquake. Therefore, the continuous decline trend of soil gas may be crucial information for medium-term earthquake preparation in the seismogenic zone, and the trend of turning upward after continuous decline is a significant signal of short-term seismogenic event in far-field. This research could improve the understanding of the anomalous features of soil gas precursors and tracking the active sections of the fault. According to the model, the earthquake area canseismic source area, the surrounding medium area be divided into three sections: the seismic source area, the surrounding medium area, and the fracture fragmentation area.

RNA modification in cardiovascular disease: implications for therapeutic interventions.

Cardiovascular disease (CVD) is the leading cause of death in the world, with a high incidence and a youth-oriented tendency. RNA modification is ubiquitous and indispensable in cell, maintaining cell homeostasis and function by dynamically regulating gene expression. Accumulating evidence has revealed the role of aberrant gene expression in CVD caused by dysregulated RNA modification. In this review, we focus on nine common RNA modifications: N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) RNA editing, and modifications of U34 on tRNA wobble. We summarize the key regulators of RNA modification and their effects on gene expression, such as RNA splicing, maturation, transport, stability, and translation. Then, based on the classification of CVD, the mechanisms by which the disease occurs and progresses through RNA modifications are discussed. Potential therapeutic strategies, such as gene therapy, are reviewed based on these mechanisms. Herein, some of the CVD (such as stroke and peripheral vascular disease) are not included due to the limited availability of literature. Finally, the prospective applications and challenges of RNA modification in CVD are discussed for the purpose of facilitating clinical translation. Moreover, we look forward to more studies exploring the mechanisms and roles of RNA modification in CVD in the future, as there are substantial uncultivated areas to be explored.

Adropin deficiency worsens TNBS-induced colitis.

The aim of this study was to describe the effects of adropin deficiency on the distribution, phenotype and pathological phenotype of macrophages in colonic and mesenteric tissues of AdrKO (Enho-/-) mice, so as to explore the mechanism of adropin deficiency in spontaneous and experimental colitis. In this study, RNA-seq and metabonomics were used to screen the regulatory mechanism of adropin on the phenotypic transformation of macrophages. We found that adropin levels in active UC patients were significantly lower than those in normal subjects and remission UC patients, and at the same time, a large number of proinflammatory M1-type macrophages were infiltrated in the mesenteric tissue of colonic tissues from UC and CD patients. At the same time, spontaneous colitis occurred in Enho-/- (adropin-deficient)C57BL/6 mice, and there was an imbalance of M2 â†’ M1 polarization of macrophages in colon and mesentery of Enho-/- mice. In vivo, it has showed that adropin deficiency could exacerbate the pathological phenotype of colitis induced by TNBS. In vitro, adropin was used to intervene RAW264.7 macrophages, and then combined analysis of RNA-seq and metabolomics demonstrated that adropin regulated lipid metabolism of macrophages through PPARγ, thus promoting the repolarization of macrophages from M1 to M2. Adropin deficiency led to an imbalance in the phenotypic distribution of macrophages infiltrating the colon and mesenteric tissues, namely, an increase in M1 type, which led to the occurrence and development of colitis.

Theranostic imaging and multimodal photodynamic therapy and immunotherapy using the mTOR signaling pathway.

Tumor metastases are considered the leading cause of cancer-associated deaths. While clinically applied drugs have demonstrated to efficiently remove the primary tumor, metastases remain poorly accessible. To overcome this limitation, herein, the development of a theranostic nanomaterial by incorporating a chromophore for imaging and a photosensitizer for treatment of metastatic tumor sites is presented. The mechanism of action reveals that the nanoparticles are able to intervene by local generation of cellular damage through photodynamic therapy as well as by systemic induction of an immune response by immunotherapy upon inhibition of the mTOR signaling pathway which is of crucial importance for tumor onset, progression and metastatic spreading. The nanomaterial is able to strongly reduce the volume of the primary tumor as well as eradicates tumor metastases in a metastatic breast cancer and a multi-drug resistant patient-derived hepatocellular carcinoma models in female mice.

The Relationship Between Fear of COVID-19 and Psychological Distress in Tour Guides: The Mediating Role of Job Insecurity and the Moderating Role of Psychological Resilience.

Purpose: The COVID-19 has greatly affected the tourism industry in China, leading to an increase in psychological distress among tour guides. This study explores the mechanisms by which tour guides' fear of the COVID-19 affects psychological distress, using job insecurity as a mediating variable and psychological resilience as a moderating variable. Patients and Methods: From August 11 to 30, 2022, 447 Chinese tour guides were invited online to fill in a questionnaire, and SPSS and Mplus tools were used for statistical analysis and hypothesis testing to conduct an empirical analysis of the relationship between COVID-19 fear and psychological distress. Results: A total of 417 questionnaires (effective rate was 93.3%) were collected, among which female (n = 243) and male (41.7%) (n =174). The age concentration of participants was 46.5% between 26 and 35 years old, 9.1% under 25 years old, and 9.8% over 46 years old. Guides' fear of COVID-19 positively and significantly influenced psychological distress (ß= 0.3051), and the relationship between fear of COVID-19 and psychological distress was mediated by job insecurity (ß=0.196, 95% CI = 0.141, 0.255). In addition, psychological resilience significantly moderated the pathway from fear of COVID-19 to job insecurity and from fear of COVID-19 to guided psychological distress (ß= 0.1371; ß=0.116). Conclusion: The diversion of fear of COVID-19 and job insecurity can alleviate the psychological distress of tour guides; strengthening their own psychological construction also helps to alleviate the effects of fear of COVID-19 on job insecurity and psychological distress. The findings of the study can provide theoretical support for the prevention and counseling of psychological problems of tourism employees in public health crises.

Skp2-mediated MLKL degradation confers cisplatin-resistant in non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is the most prevalent type of cancer and the leading cause of cancer-related death. Chemotherapeutic resistance is a major obstacle in treating NSCLC patients. Here, we discovered that the E3 ligase Skp2 is overexpressed, accompanied by the downregulation of necroptosis-related regulator MLKL in human NSCLC tissues and cell lines. Knockdown of Skp2 inhibited viability, anchorage-independent growth, and in vivo tumor development of NSCLC cells. We also found that the Skp2 protein is negatively correlated with MLKL in NSCLC tissues. Moreover, Skp2 is increased and accompanied by an upregulation of MLKL ubiquitination and degradation in cisplatin-resistant NSCLC cells. Accordingly, inhibition of Skp2 partially restores MLKL and sensitizes NSCLC cells to cisplatin in vitro and in vivo. Mechanistically, Skp2 interacts and promotes ubiquitination-mediated degradation of MLKL in cisplatin-resistant NSCLC cells. Our results provide evidence of an Skp2-dependent mechanism regulating MLKL degradation and cisplatin resistance, suggesting that targeting Skp2-ubiquitinated MLKL degradation may overcome NSCLC chemoresistance.