Promising natural products targeting protein tyrosine phosphatase SHP2 for cancer therapy.

The development of Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors is a hot spot in the research and development of antitumor drugs, which may induce immunomodulatory effects in the tumor microenvironment and participate in anti-tumor immune responses. To date, several SHP2 inhibitors have made remarkable progress and entered clinical trials for the treatment of patients with advanced solid tumors. Multiple compounds derived from natural products have been proved to influence tumor cell proliferation, apoptosis, migration and other cellular functions, modulate cell cycle and immune cell activation by regulating the function of SHP2 and its mutants. However, there is a paucity of information about their diversity, biochemistry, and therapeutic potential of targeting SHP2 in tumors. This review will provide the structure, classification, inhibitory activities, experimental models, and antitumor effects of the natural products. Notably, this review summarizes recent advance in the efficacy and pharmacological mechanism of natural products targeting SHP2 in inhibiting the various signaling pathways that regulate different cancers and thus pave the way for further development of anticancer drugs targeting SHP2.

The role of photobiomodulation in accelerating bone repair.

Bone repair is faced with obstacles such as slow repair rates and limited bone regeneration capacity. Delayed healing even nonunion could occur in bone defects, influencing the life quality of patients severely. Photobiomodulation (PBM) utilizes different light sources to derive beneficial therapeutic effects with the advantage of being non-invasive and painless, providing a promising strategy for accelerating bone repair. In this review, we summarize the parameters, mechanisms, and effects of PBM regulating bone repair, and further conclude the current clinical application of PBM devices in bone repair. The wavelength of 635-980 nm, the output power of 40-100 mW, and the energy density of less than 100 J/cm2 are the most commonly used parameters. New technologies, including needle systems and biocompatible and implantable optical fibers, offer references to realize an efficient and safe strategy for bone repair. Further research is required to establish the reliability of outcomes from in vivo and in vitro studies and to standardize clinical trial protocols.

Methyl rosmarinate is an allosteric inhibitor of SARS-CoV-2 3 CL protease as a potential candidate against SARS-cov-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been ongoing for more than three years and urgently needs to be addressed. Traditional Chinese medicine (TCM) prescriptions have played an important role in the clinical treatment of patients with COVID-19 in China. However, it is difficult to uncover the potential molecular mechanisms of the active ingredients in these TCM prescriptions. In this paper, we developed a new approach by integrating the experimental assay, virtual screening, and the experimental verification, exploring the rapid discovery of active ingredients from TCM prescriptions. To achieve this goal, 4 TCM prescriptions in clinical use for different indications were selected to find the antiviral active ingredients in TCMs. The 3-chymotrypsin-like protease (3CLpro), an important target for fighting COVID-19, was utilized to determine the inhibitory activity of the TCM prescriptions and single herb. It was found that 10 single herbs had better inhibitory activity than other herbs by using a fluorescence resonance energy transfer (FRET) - based enzymatic assay of SARS-CoV-2 3CLpro. The ingredients contained in 10 herbs were thus virtually screened and the predicted active ingredients were experimentally validated. Thus, such a research strategy firstly removed many single herbs with no inhibitory activity against SARS-CoV-2 3CLpro at the very beginning by FRET-based assay, making our subsequent virtual screening more effective. Finally, 4 active components were found to have stronger inhibitory effects on SARS-CoV-2 3CLpro, and their inhibitory mechanism was subsequently investigated. Among of them, methyl rosmarinate as an allosteric inhibitor of SARS-CoV-2 3CLpro was confirmed and its ability to inhibit viral replication was demonstrated by the SARS-CoV-2 replicon system. To validate the binding mode via docking, the mutation experiment, circular dichroism (CD), enzymatic inhibition and surface plasmon resonance (SPR) assay were performed, demonstrating that methyl rosmarinate bound to the allosteric site of SARS-CoV-2 3CLpro. In conclusion, this paper provides the new ideas for the rapid discovery of active ingredients in TCM prescriptions based on a specific target, and methyl rosmarinate has the potential to be developed as an antiviral therapeutic candidate against SARS-CoV-2 infection.

Mechanistic insights into aniline-induced liver injury: Role of the mmu_circ_26984/Myh9/NLRP3 axis and modulation by N-acetylcysteine.

Aniline is a widely used chemical. Chronic or high-dose exposure to aniline can lead to hepatocellular damage. Although the hepatic pathogenicity of aniline has been established in previous studies, studies involving pathogenic genes during aniline-induced liver injury are limited. Our study first discovered and identified the role and mechanism underlying a new circRNA mmu_circ_26984 in aniline-induced chemical liver injury. Further, we discuss the protective effect of N-acetylcysteine (NAC) in this pathway. After constructing in vitro and in vivo models of aniline treatment, we screened the circRNA with significant differences in expression in AML12 cells from control and aniline-treated groups by circRNA microarray analysis. Next, using RNA pulldown, liquid chromatography-mass spectrometry (LC-MS), and RNA immunoprecipitation, we analyzed the relationship between mmu_circ_26984 and myosin heavy chain 9 (Myh9). Subsequently, we determined the specific mechanism of action of mmu_circ_26984 and Myh9 in aniline-induced liver injury and the protective effect of NAC against aniline-induced liver injury process using Cell Counting Kit-8, Western blot, RNA extraction, a reverse transcription quantitative polymerase chain reaction (RT-qPCR), fluorescence in situ hybridization, immunohistochemistry, and immunofluorescence. The expression of mmu_circ_26984 was significantly increased in liver tissues and AML12 cells of aniline-treated mice compared with the control group. This high expression of mmu_circ_26984 increased the expression of injury-related inflammatory factors, such as NLRP3, Caspase-1, IL-18, and IL-1ß in vivo and ex vivo, which exacerbated the level of liver injury. The interaction of mmu_circ_26984 with Myh9 also affected the course of liver injury. Mmu_circ_26984 overexpression and reduced treatment affected the levels of Myh9 expression in AML12 cells, as well as downstream inflammatory factors associated with injury, such as NLRP3. In addition, NAC reduced the process of liver injury mediated by the mmu_circ_26984/Myh9/NLRP3 axis. In conclusion, mmu_circ_26984 is a potential molecular marker and therapeutic target in the process of aniline-induced liver injury that can mediate aniline-exposure-induced liver injury via modulation of the mmu_circ_26984/Myh9/NLRP3 axis, and NAC can effectively attenuate the effect of this liver injury.

Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in medical ICU patients during entire hospitalisation: a four-arm multicentre randomised controlled trial.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.

A facile, flexible, and multifunctional thermo-chemotherapy system for customized treatment of drug-resistant breast cancer.

Anticancer drug resistance invariably emerges and poses a significant barrier to curative therapy for various breast cancers. This results in a lack of satisfactory therapeutic medicine for cancer treatment. Herein, a universal vector system for drug-resistance breast cancer was designed to meet the needs of reversed multidrug resistance, thermo-chemotherapy, and long-term drug release behavior. The vector system comprises polycaprolactone (PCL) nanofiber mesh and magnetic nanoparticles (MNPs). PCL has excellent biocompatibility and electrospinning performance. In this study, MNPs were tailored to be thermogenic in response to an alternating magnetic field (AMF). PCL nanofiber can deliver various chemotherapy drugs, and suitable MNPs encapsulated in the nanofiber can generate hyperthermia and synergistic effect with those chemotherapy drugs. Therefore, a more personalized treatment system can be developed for different breast malignancies. In addition, the PCL nanofiber mesh (NFM) enables sustained release of the drugs for up two months, avoiding the burden on patients caused by repeated administration. Through model drugs doxorubicin (DOX) and chemosensitizers curcumin (CUR), we systematically verified the therapeutic effect of DOX-resistance breast cancer and inhibition of tumor generation in vivo. These findings represent a multifaceted platform of importance for validating strategic reversed MDR in pursuit of promoted thermo-chemotherapeutic outcomes. More importantly, the low cost and excellent safety and efficacy of this nanofiber mesh demonstrate that this can be customized multi-function vector system may be a promising candidate for refractory cancer therapy in clinical.

[Contamination and dietary exposure assessment of 2-chloropropanol esters in vegetable oils available on Zhejiang market during 2016-2020].

OBJECTIVE: To investigate the occurrence data for 2-chloropropanol(2-MCPD) ester in edible vegetable oils purchased in Zhejiang Province during 2016-2020, and to estimate dietary exposures of 2-MCPD ester via vegetable oil. METHODS: A total of 404 samples of edible oils were collected from markets, stores, online shopping in Zhejiang Province, the occurrence of 2-MCPD ester was detected by gas chromatography mass spectrometry from 2016-2020. Data of vegetable oils consumption was obtained from the survey result of urban and rural residents in Zhejiang Province in 2008. The exposure levels of 2-chloropropanol ester was calculated for people aged 4-6, 7-10, 11-17, 18-59 and 60 years old and older from the consumption of vegetable oils. RESULTS: The detection rate of 2-MCPD esters in 404 samples was 82.7%(334/404) with the mean level of 0.32 mg/kg. Among them, the mean content of camellia oil was the highest with 1.23 mg/kg, followed by rice oil(0.69 mg/kg); sunflower oil, olive oil and soybean oil have relatively low average values, respectively with 0.11, 0.12 and 0.13 mg/kg. There are significant differences in 2-MCPD ester content in different types of edible oils of the same brand(P<0.05), the content of 2-MCPD ester in different brands of peanut oil was significant(P<0.05), but in different brands of corn oil was not statistically significant. Among the edible vegetable oil consumers, the average exposure of 2-MCPD esters in different age groups ranged from 0.21 to 0.69 µg/(kg·BW·d). CONCLUSION: 2-MCPD esters pollution is widespread in vegetable oils, the severity of pollution was affected by the type and brand of the edible vegetable oil, and the intake of 2-MCPD esters was relatively high among people with high vegetable oil consumption and the general population of 4-10 years old.

The Effects and Mechanisms of PBM Therapy in Accelerating Orthodontic Tooth Movement.

Malocclusion is one of the three major diseases, the incidence of which could reach 56% of the imperiled oral and systemic health in the world today. Orthodontics is still the primary method to solve the problem. However, it is clear that many orthodontic complications are associated with courses of long-term therapy. Photobiomodulation (PBM) therapy could be used as a popular way to shorten the course of orthodontic treatment by nearly 26% to 40%. In this review, the efficacy in cells and animals, mechanisms, relevant cytokines and signaling, clinical trials and applications, and the future developments of PBM therapy in orthodontics were evaluated to demonstrate its validity. Simultaneously, based on orthodontic mechanisms and present findings, the mechanisms of acceleration of orthodontic tooth movement (OTM) caused by PBM therapy were explored in relation to four aspects, including blood vessels, inflammatory response, collagen and fibers, and mineralized tissues. Also, the cooperative effects and clinical translation of PBM therapy in orthodontics have been explored in a growing numbers of studies. Up to now, PBM therapy has been gaining popularity for its non-invasive nature, easy operation, and painless procedures. However, the validity and exact mechanism of PBM therapy as an adjuvant treatment in orthodontics have not been fully elucidated. Therefore, this review summarizes the efficacy of PBM therapy on the acceleration of OTM comprehensively from various aspects and was designed to provide an evidence-based platform for the research and development of light-related orthodontic tooth movement acceleration devices.

FePSe3 -Nanosheets-Integrated Cryogenic-3D-Printed Multifunctional Calcium Phosphate Scaffolds for Synergistic Therapy of Osteosarcoma.

Clinical treatment of osteosarcoma encounters great challenges of postsurgical tumor recurrence and extensive bone defect. To develop an advanced artificial bone substitute that can achieve synergistic bone regeneration and tumor therapy for osteosarcoma treatment, a multifunctional calcium phosphate composite enabled by incorporation of bioactive FePSe3 -nanosheets within the cryogenic-3D-printed α-tricalcium phosphate scaffold (TCP-FePSe3 ) is explored. The TCP-FePSe3 scaffold exhibits remarkable tumor ablation ability due to the excellent NIR-II (1064 nm) photothermal property of FePSe3 -nanosheets. Moreover, the biodegradable TCP-FePSe3 scaffold can release selenium element to suppress tumor recurrence by activating of the caspase-dependent apoptosis pathway. In a subcutaneous tumor model, it is demonstrated that tumors can be efficiently eradicated via the combination treatment with local photothermal ablation and the antitumor effect of selenium element. Meanwhile, in a rat calvarial bone defect model, the superior angiogenesis and osteogenesis induced by TCP-FePSe3 scaffold have been observed in vivo. The TCP-FePSe3 scaffold possesses improved capability to promote the repair of bone defects via vascularized bone regeneration, which is induced by the bioactive ions of Fe, Ca, and P released during the biodegradation of the implanted scaffolds. The TCP-FePSe3 composite scaffolds fabricated by cryogenic-3D-printing illustrate a distinctive strategy to construct multifunctional platform for osteosarcoma treatment.

Hollow mesoporous organosilica nanoparticles reduced graphene oxide based nanosystem for multimodal image-guided photothermal/photodynamic/chemo combinational therapy triggered by near-infrared.

Developing a nanosystem that can perform multimodal imaging-guided combination therapy is highly desirable but challenging. In this study, we introduced multifunctional nanoparticles (NPs) consisting of graphene oxide-grafted hollow mesoporous organosilica loaded with the drug doxorubicin (DOX) and photosensitizers tetraphenylporphyrin (TPP). These NPs were encapsulated by thermosensitive liposomes that release their contents once the temperature exceeds a certain threshold. Metal oxide NPs grown on the graphene oxide (GO) surface served multiple roles, including enhancing photothermal efficiency, acting as contrast agents to improve magnetic resonance imaging, increasing the sensitivity and specificity of photoacoustic imaging, and catalysing hydrogen peroxide for the generation of reactive oxygen species (ROS). When locally injected, the HMONs-rNGO@Fe3 O4 /MnOx@FA/DOX/TPP NPs effectively enriched in subcutaneous Hela cell tumour of mice. The photothermal/photodynamic/chemo combination therapy triggered by near-infrared (NIR) successfully suppressed the tumour without noticeable side effects. This study presented a unique approach to develop multimodal imaging-guided combination therapy for cancer.

Consensus of Chinese experts on strengthening personalized prevention and treatment of type 2 diabetes.

Up to now, there has not yet been guidance or consensus from Chinese experts in the field of personalized prevention and treatment of type 2 diabetes. In view of the above, the endocrinology diabetes Professional Committee of Chinese Non-government Medical Institutions Association, the integrated endocrinology diabetes Professional Committee of the integrated medicine branch of Chinese Medical Doctor Association, and the diabetes education and microvascular complications group of the diabetes branch of the Chinese Medical Association organized relevant experts to discuss and reach the "Chinese expert consensus on strengthening personalized prevention and treatment of type 2 diabetes" for reference in clinical practice.

Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay.

Targeting the interaction between the spike protein receptor binding domain (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2) is a potential therapeutic strategy for treating coronavirus disease 2019 (COVID-19). However, we still lack small-molecule drug candidates for this target due to the missing knowledge in the hot spots for the protein-protein interaction. Here, we used NanoBiT technology to identify three Ginkgolic acids from an in-house traditional Chinese medicine (TCM) library, and they interfere with the S-RBD/ACE2 interplay. Our pseudovirus assay showed that one of the compounds, Ginkgolic acid C17:1 (GA171), significantly inhibits the entry of original SARS-CoV-2 and its variants into the ACE2-overexpressed HEK293T cells. We investigated and proposed the binding sites of GA171 on S-RBD by combining molecular docking and molecular dynamics simulations. Site-directed mutagenesis and surface plasmon resonance revealed that GA171 specifically binds to the pocket near R403 and Y505, critical residues of S-RBD for S-RBD interacting with ACE2. Thus, we provide structural insights into developing new small-molecule inhibitors and vaccines against the proposed S-RBD binding site.

The role and mechanism of flavonoid herbal natural products in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine that presents clinically with abdominal pain, mucopurulent stools, and posterior urgency. The lesions of UC are mainly concentrated in the rectal and colonic mucosa and submucosa. For patients with mild to moderate UC, the best pharmacological treatment includes glucocorticoids, immunosuppressants, antibiotics, and biologics, but the long-term application can have serious toxic side effects. Currently, nearly 40% of UC patients are treated with herbal natural products in combination with traditional medications to reduce the incidence of toxic side effects. Flavonoid herbal natural products are the most widely distributed polyphenols in plants and fruits, which have certain antioxidant and anti-inflammatory activities. Flavonoid herbal natural products have achieved remarkable efficacy in the treatment of UC. The pharmacological mechanisms are related to anti-inflammation, promotion of mucosal healing, maintenance of intestinal immune homeostasis, and regulation of intestinal flora. In this paper, we summarize the flavonoid components of anti-ulcerative colitis and their mechanisms reported in the past 10 years, to provide a basis for rational clinical use and the development of new anti-ulcerative colitis drugs.

Circadian clock-A promising scientific target in oral science.

The oral and maxillofacial organs play vital roles in chewing, maintaining facial beauty, and speaking. Almost all physiological processes display circadian rhythms that are driven by the circadian clock, allowing organisms to adapt to the changing environment. In recent years, increasing evidence has shown that the circadian clock system participates in oral and maxillofacial physiological and pathological processes, such as jaw and tooth development, salivary gland function, craniofacial malformations, oral carcinoma and other diseases. However, the roles of the circadian clock in oral science have not yet been comprehensively reviewed. Therefore, This paper provides a systematic and integrated perspective on the function of the circadian clock in the fields of oral science, reviews recent advances in terms of the circadian clock in oral and maxillofacial development and disease, dialectically analyzes the importance of the circadian clock system and circadian rhythm to the activities of oral and maxillofacial tissues, and focuses on analyzing the mechanism of the circadian clock in the maintenance of oral health, affecting the common diseases of the oral and maxillofacial region and the process of oral-related systemic diseases, sums up the chronotherapy and preventive measures for oral-related diseases based on changes in tissue activity circadian rhythms, meanwhile, comes up with a new viewpoint to promote oral health and human health.

Iodine map histogram metrics in early-stage breast cancer: prediction of axillary lymph node metastasis status.

Background: Variations in axillary lymph node (ALN) metastatic potential between different breast cancers lead to microscopical alterations in tumor perfusion heterogeneity. This study investigated the usefulness of histogram metrics from iodine maps in the preoperative diagnosis of metastatic ALNs in patients with early-stage breast cancer. Methods: Between October 2020 and November 2021 enhanced spectral computed tomography (CT) was performed in female patients with breast cancer. Quantitative spectral CT parameters and histogram parameters (mean, median, maximum, minimum, 10th percentiles, 90th percentiles, kurtosis, skewness, energy, range, and variance) from iodine maps were compared between patients with metastatic and nonmetastatic ALNs. Continuous variables were compared using Student's t-test or Mann-Whitney U test. Categorical variables were compared using Pearson's chi-square tests or Fisher's exact tests. Associations between ALN status and imaging features were evaluated using Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis. Results: This study included 113 female patients (62 and 51 in the ALN-negative and ALN-positive groups, respectively). Tumor size, molecular subtypes, and location differed significantly between the ALN-negative and ALN-positive groups (P<0.05). None of the quantitative spectral CT parameters of mass between metastatic and nonmetastatic ALN groups were significantly different (P>0.05). Histogram parameters of iodine maps for breast cancers, including maximum, 10th percentile, range, and energy, were significantly higher in the metastatic ALNs group compared with the nonmetastatic ALNs group (P<0.05). Multivariable logistic regression analyses showed that tumor location and energy were independent predictors of metastatic ALNs in breast cancers. The combination of independent predictors yielded an area under the curve (AUC) of 0.824 (sensitivity 72.5%; specificity 74.2%). Conclusions: Whole-lesion histogram parameters derived from spectral CT iodine maps may be used as a complementary noninvasive means for the preoperative identification of ALN metastases in patients with early-stage breast cancer.

Association Between Role Overload and Sleep Quality Among Chinese First-Line Nurses During the COVID-19 Outbreak: The Moderating Effect of Mindfulness.

BACKGROUND: Nurses working during the coronavirus disease 2019 (COVID-19) pandemic have experienced a high incidence of insomnia because of exposure to life-threatening occupational risks. Good sleep is essential for nurses to maintain their ability to care for patients with infectious diseases. PURPOSE: The aim of this study was to assess the influence of role overload on sleep quality and the moderating role of mindfulness. METHODS: A cross-sectional survey design was used in this study, which was conducted between March 20 and April 5, 2020. The survey was completed by 357 nurses who had relocated from Fujian Province to the epicenter of the outbreak in China to treat patients with COVID-19. Role overload, sleep quality, and mindfulness in these nurses were evaluated using the Role Overload Scale, Pittsburgh Sleep Quality Index, and Five-Facet Mindfulness Questionnaire, respectively. RESULTS: Hierarchical regression and other statistical methods were used to analyze the data. Role overload was shown to be positively related to poor sleep quality, and mindfulness was found to be effective in alleviating sleep disorders associated with role overload. CONCLUSIONS: The high risk of sleep disturbance among frontline nurses may be alleviated by reducing their perceived role overload. The identification of mindfulness as a moderating mechanism in the relationship between role overload and sleep quality provides new insights to improve sleep quality in nurses.

Dietary L-theanine supplementation improves lipid metabolism and antioxidant capacity in weaning piglets.

The aim of this study was to explore the effects of dietary L-theanine (LT) supplementation on lipid metabolism and antioxidant capacity in weaned piglets. Twenty-one castrated DLY weaning piglets were randomly divided into three groups: a basal diet, a basal diet supplemented with 0.05% and 0.1% LT, respectively. Our data showed that dietary LT supplementation decreased T-CHO, TG, LDL-C and apoB levels and increased apoA and HDL-C levels in serum, but decreased the hepatic TG and T-CHO contents. Dietary LT supplementation increased the antioxidant capacity in serum and liver, and significantly increased the Nrf2 mRNA level and the nucleus Nrf2 protein level, but decreased the mRNA level of keap1 in the liver. In addition, dietary LT supplementation significantly increased HSL enzyme activity and the levels of CPT1 and TBA, while decreasing the enzyme activities of LPL and FAS in the liver. Furthermore, the mRNA levels HMG-CoAR, CPT-1a and PPARα and the protein levels of phosphorylated-AMPK and PGC-1α were increased by LT. Together, our data provide the first evidence that dietary supplementation of LT could improve lipid metabolism and antioxidant capacity in the liver of weaned piglets, and the effect might be mediated by activation of AMPK and Nrf2 signaling, respectively.

COVID-19 Victimization Experience and College Students' Mobile Phone Addiction: A Moderated Mediation Effect of Future Anxiety and Mindfulness.

This study proposed a moderated mediation model to investigate the association between COVID-19 victimization experience and mobile phone addiction, the mediating role of future anxiety, and the moderating role of mindfulness. This study employed the COVID-19 victimization experience scale, the mobile phone addiction scale, a future anxiety scale, and a mindfulness scale in a survey study among Chinese college students; 840 valid questionnaires were received. The reliability and confirmatory factor analysis results showed that all four scales had good reliability and validity. Bootstrap results demonstrated that COVID-19 victimization experience significantly predicted mobile phone addiction in college students (B = 0.202, LLCI = 0.136, ULCI = 0.268). Future anxiety fully mediated the association between COVID-19 victimization experience and mobile phone addiction (B = 0.178, LLCI = 0.136, ULCI = 0.222). Mindfulness moderated the effect of COVID-19 victimization experience on the college students' future anxiety (B = 0.159, LLCI = 0.007, ULCI = 0.054). A higher level of mindfulness was more likely than a lower level of mindfulness to attenuate the effect of COVID-19 victimization experience on the college students' future anxiety. These findings broaden our understanding regarding the association between COVID-19 victimization experience and mobile phone addiction and the moderating role of mindfulness.

Rescue of obesity-induced infertility in female mice by silencing AgRP neurons.

Obesity impacts multiple sites of the hypothalamus-pituitary gland-ovary axis (HPO axis) and has become a leading cause of female infertility. However, the critical hypothalamic neurons that participate in the development of obesity-induced infertility have not been well defined yet. Previous studies suggested that metabolic-sensing agouti-related peptide-expressing (AgRP) neurons in the arcuate nucleus (ARC) are hyperactive in diet-induced obesity (DIO) mice. We hypothesize that these neurons may convey metabolic dysfunction onto the HPO axis and contribute to obesity-induced infertility's pathophysiological process. To determine if AgRP neurons in obesity play a necessary role in the development of reproductive impairment in obesity, we used the chemogenetic method to normalize the neuronal activity of AgRP neurons in DIO female mice and test if their fertility can be restored. Our results indicated that chemogenetic inhibition of AgRP neurons could fully rescue the reproductive performance of DIO female mice, as manifested by recovered sex hormonal levels, ovulation, and fecundity. Moreover, we assayed serum AgRP levels in normal-weight and obese women and found elevated AgRP levels in obese subjects, suggesting the correlation between obesity and AgRP neuronal hyperactivity. Our results indicated that AgRP neurons constitute a central node connecting metabolism and reproduction, and dysfunctions of these neurons play a crucial role in reproductive impairment induced by metabolic abnormalities.