GALNT3 in Ischemia-Reperfusion Injury of the Kidney.

BACKGROUND: Damages to subcellular organelles, such as mitochondria and endoplasmic reticulum, are well-recognized in tubular cell injury and death in acute kidney injury (AKI). However, the changes and involvement of Golgi apparatus are much less known. Here, we report the regulation and role of N-acetylgalactosaminyltransferase-3 (GALNT3), a key enzyme for protein glycosylation in Golgi apparatus, in AKI. METHODS: AKI was induced in mice by renal ischemia-reperfusion or cisplatin. In vitro, rat kidney proximal tubular cells were subjected to hypoxia/reoxygenation (H/R) injury. To determine the role of GALNT3, its specific inhibitor T3inh-1 was tested in mice, and the effects of GALNT3 overexpression as well as knockdown were examined in the rat renal proximal tubular cells. EGFR activation was induced by recombinant EGF or by overexpressing EGFR. RESULTS: GALNT3 was significantly decreased in both in vivo and in vitro models of AKI induced by renal ischemia-reperfusion and cisplatin. T3Inh-1, a specific GALNT3 inhibitor, exacerbated ischemic AKI and suppressed tubular cell proliferation in mice. Moreover, knockdown of GALNT3 increased apoptosis during H/R treatment in rat renal proximal tubular cells, while overexpression of GALNT3 attenuated H/R-induced apoptosis, further supporting a protective role of GALNT3. Mechanistically, GALNT3 contributed to O-glycosylation of epidermal growth factor receptor (EGFR) and associated EGFR signalling. Activation or overexpression of EGFR suppressed the pro-apoptotic effect of GALNT3 knockdown in H/R-treated rat renal proximal tubular cells. CONCLUSIONS: GALNT3 protected kidney tubular cells in AKI at least partially through O-glycosylation of EGFR.

Oral administration of Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 ameliorates DSS-induced colitis in mice.

Ulcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1ß, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.

A Degraded Finger Vein Image Recovery and Enhancement Algorithm Based on Atmospheric Scattering Theory.

With the development of biometric identification technology, finger vein identification has received more and more widespread attention for its security, efficiency, and stability. However, because of the performance of the current standard finger vein image acquisition device and the complex internal organization of the finger, the acquired images are often heavily degraded and have lost their texture characteristics. This makes the topology of the finger veins inconspicuous or even difficult to distinguish, greatly affecting the identification accuracy. Therefore, this paper proposes a finger vein image recovery and enhancement algorithm using atmospheric scattering theory. Firstly, to normalize the local over-bright and over-dark regions of finger vein images within a certain threshold, the Gamma transform method is improved in this paper to correct and measure the gray value of a given image. Then, we reconstruct the image based on atmospheric scattering theory and design a pixel mutation filter to segment the venous and non-venous contact zones. Finally, the degraded finger vein images are recovered and enhanced by global image gray value normalization. Experiments on SDUMLA-HMT and ZJ-UVM datasets show that our proposed method effectively achieves the recovery and enhancement of degraded finger vein images. The image restoration and enhancement algorithm proposed in this paper performs well in finger vein recognition using traditional methods, machine learning, and deep learning. The recognition accuracy of the processed image is improved by more than 10% compared to the original image.

Isolinderalactone Ameliorates the Pathology of Alzheimer's Disease by Inhibiting the JNK Signaling Pathway.

Neuronal cell damage is a major cause of cognitive impairment in Alzheimer's disease (AD). Multiple factors, such as amyloid deposition, tau hyperphosphorylation, and neuroinflammation, can lead to neuronal cell damage. Therefore, the development of multi-target drugs with broad neuroprotective effects may be an effective strategy for the treatment of AD. Natural products have become an important source of drug discovery because of their good pharmacological activity, multiple targets, and low toxicity. In this study, we screened a natural compound library and found that the fat-soluble sesquiterpene natural compound isolinderalactone (Iso) extracted from the dried root pieces of Lindera aggregata had the ability to alleviate cellular damage induced by ß-amyloid-1-42 (Aß1-42). The role and mechanism of Iso in AD have not yet been reported. Herein, we demonstrated that Iso significantly reduced the level of apoptosis in PC12 cells. Besides, Iso treatment reduced amyloid deposition, neuron apoptosis, and neuroinflammation, ultimately improving the cognitive dysfunction of APP/PS1 (APPswe/PSEN 1dE9) mice. Notably, Iso-10 mg/kg showed superior improved effects in APP/PS1 mice compared with the positive control drug donepezil-5 mg/kg. Mechanistically, the results of RNA sequencing combined with Western blots showed that Iso exerted its therapeutic effect by inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway. Taken together, our findings suggest that Iso is a potential drug candidate for the treatment of AD.

Virgin coconut oil: A comprehensive review of antioxidant activity and mechanisms contributed by phenolic compounds.

Virgin coconut oil (VCO) is obtained by processing mature coconut cores with mechanical or natural methods. In recent years, VCO has been widely used in the food, pharmaceutical, and cosmetic industries because of its excellent functional activities. VCO has biological functions such as antioxidant, anti-inflammatory, antibacterial, and antiviral, and also has potential therapeutic effects on many chronic degenerative diseases. Among these functions, the antioxidant is the most basic and important function, which is mainly determined by phenolic compounds and medium-chain fatty acids (MCFAs). This review aims to elucidate the antioxidant functions of each phenolic compound in VCO, and discuss the antioxidant mechanisms of VCO in terms of the role of phenolic compounds with fat, intestinal microorganisms, and various organs. Besides, the composition of VCO and its application in various industries are summarized, and the biological functions of VCO are generalized, which should lay a foundation for further research on the antioxidant activity of VCO and provide a theoretical basis for the development of food additives with antioxidant activity.

Icariin protects bone marrow mesenchymal stem cells in aplastic anemia by targeting MAPK pathway.

BACKGROUND: Icariin, the main pharmacological active flavonoid extracted from Epimedi herba, can regulate cellular processes in diverse diseases. The aim of this study was to explore the effects and mechanisms of icariin on proliferation and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) in aplastic anemia (AA). METHODS AND RESULTS: Bone marrow mesenchymal stem cells were isolated from posterior tibias and femurs of AA rats that were induced by benzene and cyclophosphamide and gavaged with icariin. The isolated BMSCs were characterized morphologically and immunologically by positive markers (CD29 and CD90) and negative markers (CD34 and CD45). CCK-8 assay was performed to examine the BMSCs proliferation. Cell apoptosis and cell cycle were detected by flow cytometry. Oil red O staining was carried out to evaluate the adipogenesis of BMSCs. The mRNA expression of PPARγ, C/EBP-α, and FABP4 was measured by qRT-PCR. The protein levels of p-p38/p38, p-JNK/JNK, p-ERK/ERK, PPARγ, C/EBP-α, and FABP4 were detected using Western blotting. Icariin promoted the proliferation of BMSCs from AA rats in a dose-dependent manner. The protein levels of p-p38/p38, p-JNK/JNK, and p-ERK/ERK were downregulated in BMSCs from AA rats after icariin treatment. Icariin inhibited the apoptosis and arrested cell cycle at G/S phase of BMSCs from AA rats. The adipogenesis of BMSCs from AA rats was also suppressed after icariin treatment. However, the effects of icariin on BMSCs were weakened by p38 agonist addition. CONCLUSIONS: Icariin promoted the proliferation and inhibited the apoptosis and adipogenesis of BMSCs in AA by suppressing MAPK pathway.

Comparison of the outcome of different bone grafts combined with modified core decompression for the treatment of ARCO II stage femoral head necrosis.

PURPOSE: Treatment of ONFH at an early stage is a challenging issue. The modified minimally invasive core decompression combined with bone graft implantation remains controversial. This study aimed to compare the early-middle outcomes of four groups with different bone grafts. METHODS: A total of 182 patients (192 hips) with ONFH at the ARCO II stage were randomly divided into four groups. The free fibular graft group (FFG), free vascularized fibular graft group (FVFG), autologous iliac bone group (ABG), and ß-tricalcium bioceramics phosphate graft (ß-TCPG) group. Each group was treated with the modified minimally invasive core decompression and bone graft implantation. The operation time and blood loss were recorded by the same observer. The clinical outcome was evaluated by the Harris Hip Score and VAS score (before, 14 days after surgery, and at the last follow-up). The radiographic progression of ONFH was evaluated at least 36 months of follow-up. RESULTS: All cases were successful without any complications after the operation. The patients were followed up for 42 to 48 (44.62 ± 1.81) months. There were statistically significant differences among the four groups in operation time (F value = 1520.67; P < 0.01) and blood loss (F value = 5366.81; P < 0.01). The Harris Hip Score in each group was improved significantly from pre-operation to last follow-up (all P < 0.01). At the last follow-up, the difference in the Harris Hip Score in each group was not statistically significant (F value = 0.54; P = 0.984). The VAS scores in each group were decreased significantly from the pre-operation to14 days after surgery (all P < 0.01). At 14 days after surgery, the difference in the VAS score in each group was not statistically significant (F value = 0.64; P = 0.59). At the last follow-up, three hips collapsed on the femoral head in the FFG group, two in the FVFG group, two in the ABG group, and three in the ß-TCPG group. CONCLUSION: The four different bone graft implantation showed satisfactory early-middle outcomes. As compared to other bone grafts, the ß-TCP bioceramics graft has the advantages of shorter operation time and lesser blood loss. It may be a choice as a bone graft for the treatment of ONFH at an early stage.

Simultaneous bilateral femoral neck fractures in a dialysis-dependent patient: case report and literature review.

BACKGROUND: Simultaneous bilateral femoral neck fractures are extremely rare without obvious injury. Herein, we report the case of a patient on dialysis presenting with bilateral femoral neck fractures, which is a condition with high complication and mortality rates according to a review of the pertinent literature. CASE PRESENTATION: We report the case a 47-year-old female with a history of 8 years of haemodialysis due to polycystic kidney disease who presented with bilateral hip pain during walking. The clinical history and results of physical and radiographic examinations of this patient are shown. Single-stage bilateral hemiarthroplasty was performed after a multidisciplinary team consultation. Three days after the operation, she could ambulate with a walker. The woman gradually regained her previous ability to walk over 6 months after surgery. CONCLUSIONS: A multidisciplinary team consultation for perioperative management is necessary and effective in patients on dialysis. Early diagnosis with prompt surgical treatment could lead to favourable recovery.

The effect of posterior capsule repair in total hip arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Prior studies have compared the posterior capsule repair group in primary total hip arthroplasty by posterior approach with the control group without posterior capsule repair suggesting that the posterior capsule repair group had better clinical outcomes. However, it is still a controversy which treatment is more helpful for hip diseases. The purpose of our article is to obtain the postoperative outcomes between the 2 procedures. METHODS: We performed a systematic search by browsing the MEDLINE, EMBASE, Cochrane Library. There is no restriction on the date of publication. Before we submit our manuscript, we have re-searched the literatures again, including the articles which directly compared the postoperative outcomes of the 2 procedures. RESULTS: A total of 8 comparative studies were included in our meta-analysis. The posterior capsule repair group showed less dislocation rate, higher HHS, and even less postoperative bleeding volume. Meanwhile, there is no significant difference in ROM between 2 groups. CONCLUSION: In conclusion, according to current evidences, repairing posterior capsule during primary THA may have better functional outcomes, less dislocation incidence, and less loss of blood.

Comparison of different bone graft with arthroscopy-assisted arthrodesis for the treatment of traumatic arthritis of the subtalar joint.

AIM OF THE STUDY: To compare the clinical outcomes of traumatic arthritis of the subtalar joint treated by arthroscopy-assisted arthrodesis with autologous bone graft, allogenous bone graft, artifical bone graft, and no bone graft . METHODS: Sixty-two patients (64 ft) with traumatic arthritis of subtalar joint were randomly divided into four groups. The cases treated with arthroscopy-assisted arthrodesis were analyzed retrospectively. The mean follow-up time was about 22 months (18-28 months) in each group. Clinical outcomes were assessed by the American Orthopaedic Foot and Ankle Society (AOFAS) score, Visual Analog Scale (VAS), and radiographic examination. The post-operative complications in each group were recorded respectively. RESULTS: All operations were successful, without incision complications. The subtalar joint obtained full osseous fusion in each group. The average time of osseous fusion was about 12 weeks. There was no significant difference in the fusion time with each group (P = 0.991). The AOFAS and VAS scores in each group were improved significantly in the pre-operative vs post-operative evaluation (all P < 0.01). The average operation time in autologous bone graft group was 74.56 ± 11.45 min which significantly different from that of other groups(P < 0.01). CONCLUSION: Similar clinical outcomes were achieved among each type of bone graft. Therefore, which types of bone graft or not may be not the most important for arthroscopy-assisted subtalar arthrodesis.

The regulatory roles of VEGF-Notch signaling pathway on aplastic anemia with kidney deficiency and blood stasis.

OBJECTIVE: Vascular endothelial growth factor (VEGF)-Notch signaling pathway plays an important role in aplastic anemia (AA). This study aimed to evaluate the regulatory roles of VEGF-Notch signaling pathway on mesenchymal stem cells (MSCs) isolated from AA patients with kidney deficiency and blood stasis (KB) (AA MSCs). METHODS: Expression of VEGF-Notch signaling related factors, including VEGF, VEGFR, Notch-1, Jagged1, Delta-like1, and hes1 was detected in bone marrow (BM) tissues and AA MSCs by Western blot analysis. VEGF (100 ng/mL) and γ-secretase inhibitor (DAPT) (10 µM) was used to active and inhibit VEGF-Notch signaling in AA MSCs, respectively. After treatment, the proliferation, apoptosis, and adipogenic differentiation of AA MSCs was detected by Cell Counting Kit-8, flow cytometry, and Oil red O staining, respectively. Lentivirus short hairpin RNA (shRNA) were constructed to downregulate Notch-1 and VEGF in normal bone marrow mesenchymal stem cells (BMSCs), and the effects of VEGF/Notch-1 shRNA transfected BMSCs on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated. RESULTS: Significantly lower expression of VEGF, VEGFR, Notch-1, Jagged1, Delta-like1, and hes1 was revealed in AA BM tissues and AA MSCs when compared with the normal control (P < 0.05). The intervention of DAPT significantly inhibited the proliferation, and promoted the apoptosis and adipogenic differentiation of AA MSCs, while VEGF intervention exhibited opposite results (P < 0.05). Meanwhile, the proliferation, migration, and angiogenesis of HUVECs were significantly promoted by normal BMSCs, while inhibited by VEGF/Notch-1 shRNA transfected BMSCs (P < 0.05). CONCLUSION: The activation of VEGF-Notch signaling pathway may be a potential therapeutic target for AA with KB.

The influences of anesthesia methods on some complications after orthopedic surgery: a Bayesian network meta-analysis.

BACKGROUND: Although several anesthesia procedures have been explored for orthopedic surgery, the complications of anesthesia remain not well resolved. This study aimed to explore the influence of different anesthesia methods on the complications after orthopedic surgery. METHODS: According to the searching strategy, anesthesia associated studies in orthopedic surgery were screened from Pubmed, Embase, and the Cochrane Library up to Mar. 10th, 2018. Then, complications and demographic data were extracted and quality of studies was assessed using Cochrane Collaboration recommendations. ADDIS software was used to perform the network meta-analysis. Pooled effect size was calculated using random effective model or consistency model, and presented with odds ratio (OR) and 95% confidence interval (CI). RESULTS: According to the selective criteria, a total of 23 studies with 2393 patients were enrolled in this study. Quality assessment revealed all studies had an ordinary quality. Network meta-analyses revealed that nerve block analgesia (NBA) presented a lower effect on the occurrence of post-operative nausea or vomiting (PONV; OR = 0.17, 95% CI: 0.06-0.39) and urine retention (OR = 0.07, 95% CI: 0.01-0.37) compared with epidural anesthesia (EA). Interscalene block (ISB) and local infiltration analgesia (LIA) could significantly reduce the occurrence of back pain compared with EA (OR = 0.00, 95% CI = 0.00-0.30; OR = 0.00, 95% CI = 0.00-0.25). CONCLUSION: NBA presented an effective role in reliving the occurrence of PONV and urine retention, and ISB and LIA relieved the back pain compared with EA after orthopedic surgery.

Exploring the Mechanisms of Sanguinarine in the Treatment of Osteoporosis by Integrating Network Pharmacology Analysis and Deep Learning Technology.

BACKGROUND: Sanguinarine (SAN) has been reported to have antioxidant, antiinflammatory, and antimicrobial activities with potential for the treatment of osteoporosis (OP). OBJECTIVE: This work purposed to unravel the molecular mechanisms of SAN in the treatment of OP. METHODS: OP-related genes and SAN-related targets were predicted from public databases. Differential expression analysis and VennDiagram were adopted to detect SAN-related targets against OP. Protein-protein interaction (PPI) network was served for core target identification. Molecular docking and DeepPurpose algorithm were further adopted to investigate the binding ability between core targets and SAN. Gene pathway scoring of these targets was calculated utilizing gene set variation analysis (GSVA). Finally, we explored the effect of SAN on the expressions of core targets in preosteoblastic MC3T3-E1 cells. RESULTS: A total of 21 candidate targets of SAN against OP were acquired. Furthermore, six core targets were identified, among which CASP3, CTNNB1, and ERBB2 were remarkably differentially expressed in OP and healthy individuals. The binding energies of SAN with CASP3, CTNNB1, and ERBB2 were -6, -6.731, and -7.162 kcal/mol, respectively. Moreover, the GSVA scores of the Wnt/calcium signaling pathway were significantly lower in OP cases than in healthy individuals. In addition, the expression of CASP3 was positively associated with Wnt/calcium signaling pathway. CASP3 and ERBB2 were significantly lower expressed in SAN group than in DMSO group, whereas the expression of CTNNB1 was in contrast. CONCLUSION: CASP3, CTNNB1, and ERBB2 emerge as potential targets of SAN in OP prevention and treatment.

Elucidating Cyathula Officinals' mechanism in osteoarthritis treatment: Network pharmacology and empirical evidence on anti-inflammatory actions.

In this study, we explored the therapeutic potential of Cyathula Officinals (CNX) in Knee Osteoarthritis (KOA) treatment. Utilizing network pharmacology and in vitro experiments, we identified active ingredients, action targets and pathways in CNX. Our analysis, integrating databases like TCMSP, SwissTarget Prediction, Genecards, CTD, STRING, and DAVID, highlighted 396 action targets and 283 disease targets, pinpointing 64 intersection genes linked to KOA. The significant involvement of the MAPK and NF-κB pathways in CNX's anti-inflammatory action was validated through qPCR, which might underlie CNX's efficacy in inhibiting chondrocyte apoptosis and IL-6 expression. These findings suggest CNX's potential in KOA management, offering insights for its clinical application.

One-step, reagent-free construction of nano-enzyme as visual and reusable biosensor for oxidase substrates.

The substrates of oxidase are biologically essential substances that are closely associated with human physiological health. However, current biosensing methods suffer from tough recyclability and undesired denaturation of enzyme due to impurity interference. Herein, we have developed a visual and reusable biosensor for detecting substrate using glucose oxidase (GOx) as a model oxidase. GOx was immobilized onto gold nanoparticles (AuNPs) at -20 °C in one step without additional reagents. The resulting nano-enzyme generated coloimetric signals by coupling with horseradish peroxidase (HRP) using TMB as the substrate. Our results demonstrated that the immobilized GOx exhibited satisfactory sensitivity (0.68 µM) for glucose detection and higher inherent stability than free GOx under harsh conditions, enabling reliable detection of glucose in complex fluids (colored beverages and saliva). Furthermore, the nano-enzyme retained 80 % activity even after four cycles of catalytic oxidation. This strategy constructs a universal biosensor for substrates with nano-enzyme which rely only on intrinsic cysteine within the oxidase while avoiding functional handle modification.

Ginsenoside RK3 promotes neurogenesis in Alzheimer's disease through activation of the CREB/BDNF pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In the ancient book "Shen Nong's Herbal Classic," Panax ginseng CA Mey was believed to have multiple benefits, including calming nerves, improving cognitive function, and promoting longevity. Ginsenosides are the main active ingredients of ginseng. Ginsenoside RK3 (RK3), a rare ginsenoside extracted from ginseng, displays strong pharmacological potential. However, its effect on neurogenesis remains insufficiently investigated. AIM OF THE STUDY: This study aims to investigate whether RK3 improves learning and memory by promoting neurogenesis, and to explore the mechanism of RK3 action. MATERIALS AND METHODS: The therapeutic effect of RK3 on learning and memory was determined by the Morris water maze (MWM) and novel object recognition test (NORT). The pathogenesis and protective effect of RK3 on primary neurons and animal models were detected by immunofluorescence and western blotting. Protein expression of cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway was detected by western blotting. RESULTS: Our results showed that RK3 treatment significantly improved cognitive function in APPswe/PSEN1dE9 (APP/PS1) mice and C57BL/6 (C57) mice. RK3 promotes neurogenesis and synaptogenesis in the mouse hippocampus. In vitro, RK3 prevents Aß-induced injury in primary cultured neurons and promotes the proliferation of PC12 as well as the expression of synapse-associated proteins. Mechanically, the positve role of RK3 on neurogenesis was combined with the activation of CREB/BDNF pathway. Inhibition of CREB/BDNF pathway attenuated the effect of RK3. CONCLUSION: In conclusion, this study demonstrated that RK3 promotes learning and cognition in APP/PS1 and C57 mice by promoting neurogenesis and synaptogenesis through the CREB/BDNF signaling pathway. Therefore, RK3 is expected to be further developed into a potential drug candidate for the treatment of Alzheimer's disease (AD).

Bioorthogonal targeted cell membrane vesicles/cell-sheet composites reduce postoperative tumor recurrence and scar formation of melanoma.

While surgical resection is the predominant clinical strategy in the treatment of melanoma, postoperative recurrence and undetectable metastasis are both pernicious drawbacks to this otherwise highly successful approach. Furthermore, the deep cavities result from tumor excision can leave long lasting wounds which are slow to heal and often leave visible scars. These unmet needs are addressed in the present work through the use of a multidimensional strategy, and also promotes wound healing and scar reduction. In the first phase, cell membrane-derived nanovesicles (NVs) are engineered to show PD-1 and dibenzocyclooctyne (DBCO). These are capable of reactivating T cells by blocking the PD-1/PD-L1 pathway. In the second phase, azido (N3) labeled mesenchymal stem cells (MSCs) are cultured into cell sheets using tissue engineering, then apply directly to surgical wounds to enhance tissue repair. Owing to the complementary association between DBCO and N3 groups, PD-1 NVs were accumulated at the site of excision. This strategy can inhibit postoperative tumor recurrence and metastasis, whilst also promoting wound healing and reducing scar formation. The results of this study set a precedent for a new and innovative multidimensional therapeutic strategy in the postoperative treatment of melanoma.

How does the double-track human resource management model contribute to job burnout and mental health among Chinese government departments? A Chinese police study.

Objectives: This study aims to investigate the contribution of the double-track human resource management model to the job performance and mental health of frontline police within China's public security organs. Methodology: An individual-centered approach, latent profile analysis (LPA), was utilized in this study, which used cluster sampling to survey all police of all 118 frontline police stations in an economically underdeveloped area of China and 839 personnel were selected for the analysis. This method allowed for a detailed examination of the contribution of the double-track system to job performance and mental health. Findings and conclusion: The study identified three subtypes of job burnout among Chinese police: low job burnout, medium job burnout, and emotional exhaustion type. The double-track human resource management model in China's public security organs has contributed to significant disparities between civilian and auxiliary police, such as more severe job burnout among civilian police, lower job performance, and mental health among auxiliary police. Implications: To mitigate the potential risks associated with the double-track human resource management model, adjustments are necessary for both the management system and the treatment distribution system, which would also help address the disparities and improve the overall wellbeing and performance of all police officers.

Norboldine improves cognitive impairment and pathological features in Alzheimer's disease by activating AMPK/GSK3ß/Nrf2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Lindera aggregata (Sims) Kosterm is a common traditional herb that has multiple bioactivities. Radix Linderae (LR), the dry roots of Lindera aggregata (Sims) Kosterm, is a traditional Chinese herbal medicine with antioxidant, anti-inflammatory and immunomodulatory properties, first found in Kaibao Era. Norboldine (Nor) is an alkaloid extracted from LR and is one of the primary active ingredients of LR. However, the pharmacological functions and mechanism of Nor in Alzheimer's disease (AD) are still unknown. AIM OF THE STUDY: This study aims to investigate the effect and mechanism of Nor therapy in improving the cognitive impairment and pathological features of 3 × Tg mice. MATERIALS AND METHODS: 3 × Tg mice were treated with two concentrations of Nor for one month and then the memory and cognitive abilities of mice were assessed by novel object recognition experiment and Morris water maze. The impact of Nor on the pathology of ADwere examined in PC12 cells and animal tissues using western blotting and immunofluorescence. Finally, western blotting was used to verify the anti-apoptotic effect of Nor by activating AMPK/GSK3ß/Nrf2 signaling pathway at animal and cellular levels. RESULTS: In this study, we showed that Nor treatment improved the capacity of the learning and memory of 3 × Tg mice and alleviated AD pathology such as Aß deposition. In addition, Nor restored the abnormalities of mitochondrial membrane potential, significantly reduced the production of intracellular ROS and neuronal cell apoptosis. Mechanistically, we combined network pharmacology and experimental verification to show that Nor may exert antioxidant stress and anti-apoptotic through the AMPK/GSK3ß/Nrf2 signaling pathway. CONCLUSION: Our data provide some evidence that Nor exerts a neuroprotective effect through the AMPK/GSK3ß/Nrf2 pathway, thereby improving cognitive impairment in AD model mice. Natural products derived from traditional Chinese medicines are becoming increasingly popular in the process of new drug development and discovery, and our findings provide new perspectives for the discovery of improved treatment strategies for AD.

The relationship between the psychological resilience and post-traumatic growth of college students during the COVID-19 pandemic: a model of conditioned processes mediated by negative emotions and moderated by deliberate rumination.

BACKGROUND: The mental health of university students during the COVID-19 pandemic has attracted the attention of researchers. For the present study researchers constructed a mediation model to explore the relationship between psychological resilience and post-traumatic growth, the mediating role of negative emotions and the moderating role of deliberate rumination in students. METHODS: The Psychological Resilience Scale, Posttraumatic Growth Inventory, Depression-Anxiety-Stress Scale (DASS-21) and Event Related Rumination Inventory were used in a survey of 881 college students. The data were analyzed using SPSS 26.0 and the PROCESS plugin (version 3.3). RESULTS: (1) Psychological resilience is positively related with post-traumatic growth. Deliberate rumination is positively related to psychological resilience, posttraumatic growth, and negative emotions. Psychological resilience, post-traumatic growth and negative emotions are negatively related. (2) Negative emotions mediated the relationship between psychological resilience and post-traumatic growth. (3) Deliberate rumination plays a moderating role in psychological resilience affecting negative emotions. Deliberate rumination plays a moderating role in the extent to which psychological resilience influences PTG through negative emotions. CONCLUSIONS: Psychological resilience affects post-traumatic growth directly and also indirectly through negative emotions. With the increase of mental resilience, the level of negative emotion tended to decrease. When individuals are experiencing negative emotions, high levels of active rumination are more likely to promote post-traumatic growth. This study helps to explore the factors affecting the mental health of college students during the epidemic, thus providing guidance for appropriate mental health interventions.