Kaempferol attenuates wear particle-induced inflammatory osteolysis via JNK and p38-MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Wear particle-induced inflammatory osteoclast activation is a master contributor to periprosthetic osteolysis, which can cause pathological bone loss and destruction. Hence, inhibiting inflammation and osteoclastogenesis is an important strategy for preventing wear particle-induced osteolysis. To date, there are no FDA-approved non-surgical pharmacotherapies for arresting periprosthetic osteolysis. Kaempferol (KAE), a natural flavonol abundant in many traditional Chinese herbal medicines, has been shown to have protective effects against inflammatory bone diseases such as rheumatoid arthritis, but no previous study has evaluated the effects of KAE on wear particle-induced osteolysis. AIM OF THE STUDY: The study aimed to investigate the effects of KAE on wear particle-induced inflammatory osteolysis and osteoclast activation, and further explore the underlying mechanisms. MATERIALS AND METHODS: TiAl6V4 metal particles (TiPs) were retrieved from the prosthesis of patients who underwent revision hip arthroplasty due to aseptic loosening. A mouse calvarial osteolysis model was used to investigate the effects of KAE on wear particle-induced inflammatory osteolysis in vivo. Primary bone marrow-derived macrophages (BMMs) were used to explore the effects of KAE on osteoclast differentiation and bone-resorbing activity as well as the underlying mechanisms in vitro. RESULTS: In the present study, we found that KAE alleviated wear particle-induced inflammatory bone loss in vivo and inhibited osteoclast differentiation and function in vitro. Furthermore, we revealed that KAE exerted anti-osteoclastogenic effects by downregulating JNK and p38-MAPK signaling as well as the downstream NFATc1 expression. CONCLUSIONS: KAE is an alternative therapeutic agent for preventing and treating periprosthetic osteolysis and aseptic loosening.

Baitouweng decoction repairs the intestinal barrier in DSS-induced colitis mice via regulation of AMPK/mTOR-mediated autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is one of non-specific inflammatory bowel disease that mainly affects the colon. Recently, UC has become a significant social and economic problem worldwide. Baitouweng decoction (BD), a traditional Chinese medicine described in the "Treatise on Febrile Diseases", has been used for centuries to treat intestinal diseases. However, its underlying mechanism remains largely unexplored. AIM OF STUDY: In this study, we aimed to investigate the effect of BD on autophagy for repairing the colonic barrier in DSS-induced colitis mice and explored its role in regulating the autophagic signaling pathway AMPK/mTOR. MATERIALS AND METHODS: Mice with colitis were treated with 3% dextran sulfate sodium (DSS) for 7 days. The effectiveness of BD in treating DSS-induced colitis was evaluated through body weight, disease activity index (DAI), colon length, pathological changes, organ index, and proportion of blood cells. Moreover, intestinal epithelial permeability was analyzed by examining FITC-dextran leakage, the bacterial load of mesenteric lymph nodes (MLNs), and bacterial infiltration of colon tissues. Barrier function was evaluated by assessing the number and proportion of colonic goblet cells and the expression of tight junction proteins, including ZO-1, claudin-1, and occludin. Furthermore, the levels of autophagy were assessed by examining the number of autophagosomes and the expression of the autophagy-related proteins LC3, Beclin1, and P62. Additionally, network pharmacology research was conducted to analyze the potential mechanisms underlying the medicinal effects, as indicated by the role of AMPK/mTOR in regulating the autophagic signaling pathway. RESULTS: BD improved colitis symptoms in mice by restoring body weight and colon length and reducing inflammatory cell infiltration. Additionally, BD decreased the diffusion of FITC-dextran and bacterial translocation in MLNs, as well as bacterial infiltration of the colonic mucosa. The number and proportion of colonic goblet cells, the expression of ZO-1, Claudin-1, and Occludin, and the levels of autophagy were also increased by BD. Network pharmacology analysis suggested that BD might affect intestinal autophagy through the AMPK signaling pathway, which was confirmed by the activation of AMPK phosphorylation and the downregulation of mTOR expression following BD treatment. CONCLUSION: Our study demonstrated that BD repaired the intestinal epithelial barrier in DSS-induced colitis mice by activating AMPK phosphorylation and inhibiting mTOR expression to promote autophagy.

Geniposide protects against neurotoxicity in mouse models of rotenone-induced Parkinson's disease involving the mTOR and Nrf2 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Gardeniae, with the effects of discharging fire, eliminating vexation, reducing fever and causing diuresis, and cooling blood to remove apthogentic heat, could be used to treat Parkinson's disease (PD). Geniposide, as the main active ingredient of Fructus Gardeniae, has been shown to have neuroprotective effects in several rodent models. Rotenone, a commonly used neurotoxin, induced PD model progresses slowly, but simulates the pathological changes of PD's slow progression. AIM OF THE STUDY: Herein, we mainly investigated the neuroprotective effects of geniposide on rotenone-induced mouse model of PD and the underlined mechanism. MATERIALS AND METHODS: C57BL/6 mice were treated with rotenone (30 mg/kg, p. o.) daily for 60 days. Geniposide (25 and 50 mg/kg, p. o.) were administered at alterative day 30 min before rotenone. On day 60, the challenging beam, spontaneous activity, and adhesive removal tests were performed to evaluate the motor activity. Dopamine, DOPAC and HVA levels were detected by UPLC-MS/MS methods. Dopaminergic neurodegeneration was assessed using immunohistochemistry staining. ROS production, MDA level and GSH: GSSG ratio were measured to analyze oxidative stress. Cleavage of PARP and caspase-3 were detected to assess neuronal apoptosis. The expression of Nrf2 and mTOR signaling were detected using Western blot. RESULTS: Geniposide improved motor dysfunction, restored neurotransmitters levels, and attenuated dopaminergic neurodegeneration induced by rotenone in mice. Geniposide suppressed rotenone-induced neuronal oxidative damage associated with Nrf2 signaling, and neuronal apoptosis involving mTOR pathway. CONCLUSIONS: Geniposide may exert a neuroprotective effect in a mouse model of PD by rotenone, and this effect might be relevant to Nrf2 associated antioxidant signaling and mTOR involved anti-apoptosis pathway.

Overexpression of Pde4d in rat granulosa cells inhibits maturation and atresia of antral follicles to induce polycystic ovary.

BACKGROUND: Follicle dysplasia can cause polycystic ovary syndrome, which can lead to anovulatory infertility. This study explored gene(s) that may contribute to polycystic ovary syndrome. METHODS: Three animal models of polycystic ovary syndrome were created by treating 3-week-old rats respectively with estradiol valerate, testosterone propionate, or constant illumination for 8 weeks. Granulosa cells from the three disease groups and from healthy controls were transcriptionally profiled to identify differentially expressed genes. The phosphodiesterase-4d (Pde4d) was screened as the most promising candidate pathogenic gene. The Pde4d was overexpressed in rats via intrabursal infection with recombinant lentivirus to see the effect of Pde4d on ovarian morphology. The potential roles of the candidate gene and interactors of the encoded protein were explored using polymerase chain reaction, western blotting, transfection and co-immunoprecipitation. RESULTS: All three rat models of polycystic ovary syndrome showed polycystic ovary phenotype. Seven promising candidate genes were obtained by transcriptomics and verifications. Pde4d was further investigated because it could trigger downstream signaling pathways. The Pde4d overexpression in rat ovary induced cystic follicles. It inhibited follicle maturation through a mechanism involving inhibition of cAMP-PKA-CREB signaling. The Pde4d also inhibited phosphorylation of c-Jun N-terminal kinase to reduce apoptosis in the ovary, through a mechanism involving interaction of its poly-proline domain with the protein POSH. CONCLUSION: Upregulation of Pde4d may contribute to polycystic ovary syndrome by impeding follicle maturation and preventing apoptotic atresia.

Identifying conservation and restoration priorities for degraded coastal wetland vegetations: Integrating species distribution model and GeoDetector.

The ongoing degradation of seagrass and seaweed is of global concern. Comprehending the spatial distribution of these wetland vegetation types and the threats they face becomes critical for effective conservation and restoration efforts. In this study, we combined a species distribution model and geographical detector to propose a novel framework for mapping the distribution and disturbance of degraded coastal wetland vegetation in sparsely recorded areas and identifying conservation and restoration priorities. Guangxi is a province in China known for its extensive coastal wetland vegetation. In our study of Guangxi, habitats suitable for two degraded vegetation types, i.e., seagrass and seaweed, were mapped using the maximum entropy model; 669.44 km2 of seagrass habitat and 929.69 km2 of seaweed habitat were identified. The geographical detector model was used to analyze anthropogenic disturbance caused by four local disturbance factors: shoreline development, fisheries, waterways, and ports and anchorages. Shoreline development was identified as the disturbance factor with the strongest impact on potential habitats of both vegetation types. According to these findings, 48.40 %-64.23 % of the vegetation habitats suffered from high anthropogenic disturbance. Preexisting nature reserves had not effectively protected wetland vegetation from human disturbance. Based on the spatial pattern of vegetation habitat and comprehensive anthropogenic disturbance, conservation and restoration priorities for seagrasses and seaweeds covering an area of 302.26 km2 were further mapped. Our results thus help improve wetland vegetation conservation by providing basic information, and they provide a tool to support site planning for seagrass and seaweed conservation and restoration.

Retarding Ion Migration for Stable Blade-Coated Inverted Perovskite Solar Cells.

The fabrication of perovskite solar cells (PSCs) through blade coating is seen as one of the most viable paths toward commercialization. However, relative to the less scalable spin coating method, the blade coating process often results in more defective perovskite films with lower grain uniformity. Ion migration, facilitated by those elevated defect levels, is one of the main triggers of phase segregation and device instability. Here, we report a bifunctional molecule, p-aminobenzoic acid (PABA), which enhances the barrier to ion migration, induces grain growth along the (100) facet, and promotes the formation of homogeneous perovskite films with fewer defects. As a result, PSCs with PABA achieved impressive power conversion efficiencies of 23.32% and 22.23% for devices with active areas of 0.1 cm2 and 1 cm2 , respectively. Furthermore, these devices maintained 93.8% of their initial efficiencies after 1000 hours under 1-sun illumination, 75 °C, and 10% relative humidity conditions. This article is protected by copyright. All rights reserved.

Electroacupuncture alleviates neurological function via activating the Yap-OPA1 axis and mitochondrial fusion in rats with cerebral ischemia-reperfusion injury. / 电针通过Yesç›¸å ³è›‹ç™½-视神经萎缩蛋白1ä¿¡å·è½´æ¿€æ´»çº¿ç²’ä½“èžåˆåŠŸèƒ½å‡è½»å¤§é¼ è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the mechanism of electroacupuncture (EA) in alleviating cerebral ische-mia injury by activating the Yap-OPA1 signaling axis. METHODS: A total of 48 male SD rats were used in the present study. The focal CIRI model was established by occlusion of the middle cerebral artery and reperfusion (MCAO/R), followed by dividing the CIRI rats into model group, EA group and EA+Ver (Verteporfin, Yap antagonist) group (n=12 in each group). And another 12 normal rats were used as the sham operation group. For rats of the EA group, EA (4 Hz/20 Hz, 0.5 mA) was applied to "Baihui"(GV20) and "Shenting"(GV24) for 20 min, once daily for 7 days. The neurological deficit score (0 to 4 points) was given according to Longa's method. The infarct volume of rats in each group was assessed by TTC method, and the expression levels of Yes associated protein (Yap), Optic atrophy protein 1 (OPA1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2) proteins and mRNAs in cerebral cortex of infarcted side, as well as Bax (proapoptotic factor) and Bcl-1 (anti-apoptotic protein) proteins were detected by Westernblot, and real-time PCR, and the immunoactivity of Yap and OPA1 was detected by immunofluorescent staining. RESULTS: After modeling, the infarct volume, neurological deficit score and the expression of Bax were significantly increased (P<0.01), while the mRNA and protein expressions of Yap, OPA1, Mfn2, Mfn1, and Bcl-2 were significantly down-regulated in the model group relevant to the sham operation group (P<0.01, P<0.05). Compared with the model group, the neurological deficit score, infarct volume and the expression of Bax were significantly decreased (P<0.01), while the expression levels of Yap, OPA1, Mfn2, Mfn1 proteins and mRNAs and Bcl-2 protein, Yap and OPA1 immunofluorescence intensify were considerably up-regulated in the EA group (P<0.01, P<0.05). Following administration of Ver, the effects of EA in down-regulating the neurological score, infarct volume, and Bax expression and up-regulating the expressions of Yap, OPA1, Mfn1, Mfn2 proteins and mRNAs and Yap and OPA1 immunofluorescence intensify were eliminated. CONCLUSIONS: EA of GV20 and GV24 can improve the neurological function in rats with CIRI, which may be associated with its functions in activating mitochondrial fusion function and up-regulating Yap-OPA1 signaling axis.

Tracking of Stem Cells in Chronic Liver Diseases: Current Trends and Developments.

Stem cell therapy holds great promise for future clinical practice for treatment of advanced liver diseases. However, the fate of stem cells after transplantation, including the distribution, viability, and the cell clearance, has not been fully elucidated. Herein, recent advances regarding the imaging tools for stem cells tracking mainly in chronic liver diseases with the advantages and disadvantages of each approach have been described. Magnetic resonance imaging is a promising clinical imaging modality due to non-radioactivity, excellent penetrability, and high spatial resolution. Fluorescence imaging and radionuclide imaging demonstrate relatively increased sensitivity, with the latter excelling in real-time monitoring. Reporter genes specialize in long-term tracing. Nevertheless, the disadvantages of low sensitivity, radiation, exogenous gene risk are inevitably present in each of these means, respectively. In this review, we aim to comprehensively evaluate the current state of methods for tracking of stem cell, highlighting their strengths and weaknesses, and providing insights into their future potential. Multimodality imaging strategies may overcome the inherent limitations of single-modality imaging by combining the strengths of different imaging techniques to provide more comprehensive information in the clinical setting.

ß-Nicotinamide Mononucleotide Alleviates Hydrogen Peroxide-Induced Cell Cycle Arrest and Death in Ovarian Granulosa Cells.

Maintaining normal functions of ovarian granulosa cells (GCs) is essential for oocyte development and maturation. The dysfunction of GCs impairs nutrition supply and estrogen secretion by follicles, thus negatively affecting the breeding capacity of farm animals. Impaired GCs is generally associated with declines in Nicotinamide adenine dinucleotide (NAD+) levels, which triggers un-controlled oxidative stress, and the oxidative stress, thus, attack the subcellular structures and cause cell damage. ß-nicotinamide mononucleotide (NMN), a NAD+ precursor, has demonstrated well-known antioxidant properties in several studies. In this study, using two types of ovarian GCs (mouse GCs (mGCs) and human granulosa cell line (KGN)) as cell models, we aimed to investigate the potential effects of NMN on gene expression patterns and antioxidant capacity of both mGCs and KGN that were exposed to hydrogen peroxide (H2O2). As shown in results of the study, mGCs that were exposed to H2O2 significantly altered the gene expression patterns, with 428 differentially expressed genes (DEGs) when compared with those of the control group. Furthermore, adding NMN to H2O2-cultured mGCs displayed 621 DEGs. The functional enrichment analysis revealed that DEGs were mainly enriched in key pathways like cell cycle, senescence, and cell death. Using RT-qPCR, CCK8, and ß-galactosidase staining, we found that H2O2 exposure on mGCs obviously reduced cell activity/mRNA expressions of antioxidant genes, inhibited cell proliferation, and induced cellular senescence. Notably, NMN supplementation partially prevented these H2O2-induced abnormalities. Moreover, these similar beneficial effects of NMN on antioxidant capacity were confirmed in the KGN cell models that were exposed to H2O2. Taken together, the present results demonstrate that NMN supplementation protects against H2O2-induced impairments in gene expression pattern, cell cycle arrest, and cell death in ovarian GCs through boosting NAD+ levels and provide potential strategies to ameliorate uncontrolled oxidative stress in ovarian GCs.

Dietary tangeretin improved antibiotic-associated diarrhea in mice by enhancing the intestinal barrier function, regulating the gut microbiota, and metabolic homeostasis.

Antibiotic-associated diarrhea is mediated by antibiotic treatment and is usually caused by the disruption of the intestinal barrier, gut microbiota, and metabolic balance. To identify a dietary strategy that can mitigate the side effects of antibiotics, this study investigated the effect of tangeretin on antibiotic-associated diarrhea in C57BL/6 mice. The results revealed that dietary tangeretin significantly ameliorated symptoms of antibiotic-associated diarrhea, as evidenced by the decreased diarrhea status scores, the reduced fecal water content, the decreased caecum/body weight ratio, and the alleviated colonic tissue damage. Dietary tangeretin also exhibited a protective effect on the intestinal barrier function by upregulating the mRNA and protein expression of claudin-1 and ZO-1. Furthermore, analysis of the gut microbiota using 16S rRNA gene sequencing indicated that dietary tangeretin modulated the gut microbiota of mice with antibiotic-associated diarrhea via increasing the gut microbiota diversity and the abundance of beneficial bacteria, e.g., Lactobacillaceae and Ruminococcaceae, and decreasing the abundance of harmful bacteria, e.g., Enterococcus and Terrisporobacter. Additionally, dietary tangeretin restored the levels of short-chain fatty acids and modulated metabolic pathways by enriching purine metabolism, bile acid metabolism, ABC transporters, and choline metabolism in cancer. Collectively, these findings provide a solid scientific basis for the rational use of tangeretin as a preventive and therapeutic agent for antibiotic-associated diarrhea.

Comparative Transcriptome Analysis Reveals the Underlying Response Mechanism to Salt Stress in Maize Seedling Roots.

Crop growth and development can be impeded by salt stress, leading to a significant decline in crop yield and quality. This investigation performed a comparative analysis of the physiological responses of two maize inbred lines, namely L318 (CML115) and L323 (GEMS58), under salt-stress conditions. The results elucidated that CML115 exhibited higher salt tolerance compared with GEMS58. Transcriptome analysis of the root system revealed that DEGs shared by the two inbred lines were significantly enriched in the MAPK signaling pathway-plant and plant hormone signal transduction, which wield an instrumental role in orchestrating the maize response to salt-induced stress. Furthermore, the DEGs' exclusivity to salt-tolerant genotypes was associated with sugar metabolism pathways, and these unique DEGs may account for the disparities in salt tolerance between the two genotypes. Meanwhile, we investigated the dynamic global transcriptome in the root systems of seedlings at five time points after salt treatment and compared transcriptome data from different genotypes to examine the similarities and differences in salt tolerance mechanisms of different germplasms.

A systematic review and meta-analysis comparing the efficacy and safety of ketamine versus morphine for the treatment of acute pain.

INTRODUCTION: Ketamine is reported as a potent opioid alternative that provides significant reduction in pain with no severe adverse events. However, some studies didn't find its use satisfactory and reported less reduction in pain score with ketamine. The purpose of this study is to compare the efficacy and safety of ketamine versus morphine for the treatment of acute pain in emergency situations. EVIDENCE ACQUISITION: The PubMed, MEDLINE, PsycINFO EMBASE, Cochrane Library, PROSPERO registry platform, and ClinicalTrials.gov websites were queried in accordance with the PRISMA guidelines in order to locate relevant studies. According to the predefined PICOS criteria, articles were included and event data pertaining to changes in Visual Analog Scale or Numeric Rating Scale pain scales were extracted. Using RevMan and MedCalc, a meta-analysis was conducted to compare the effects of ketamine and morphine for the treatment of acute pain. EVIDENCE SYNTHESIS: Twelve studies met the criteria for inclusion in this meta-analysis. Ketamine was found to be more effective than morphine at reducing pain scores, with an odds ratio of 0.60 (95% CI 0.48 to 0.76). Similarly, no severe adverse events related to ketamine were reported in any study, and it has a low-risk ratio of 0.78 (95% CI 0.70 to 0.87). Egger's Test P-values (0.3052) and Begg's Test P values (0.3869) indicate a low risk of bias, and the Bland-Altman plot demonstrates a high degree of concordance. CONCLUSIONS: Ketamine is a potent and effective alternative to morphine for the management of acute pain, and it reduces pain score significantly with minimal side effects.

Toward parallel intelligence: An interdisciplinary solution for complex systems.

The growing complexity of real-world systems necessitates interdisciplinary solutions to confront myriad challenges in modeling, analysis, management, and control. To meet these demands, the parallel systems method rooted in the artificial systems, computational experiments, and parallel execution (ACP) approach has been developed. The method cultivates a cycle termed parallel intelligence, which iteratively creates data, acquires knowledge, and refines the actual system. Over the past two decades, the parallel systems method has continuously woven advanced knowledge and technologies from various disciplines, offering versatile interdisciplinary solutions for complex systems across diverse fields. This review explores the origins and fundamental concepts of the parallel systems method, showcasing its accomplishments as a diverse array of parallel technologies and applications while also prognosticating potential challenges. We posit that this method will considerably augment sustainable development while enhancing interdisciplinary communication and cooperation.

The necessity for enhancing awareness of tuberculosis starting from the early college semesters: empirical evidence from a cross-sectional research.

Background: College students, especially those in the lower grades, constitute the main high-risk population for tuberculosis (TB). Insufficient knowledge about TB among college students contributes to an increased risk of TB infection. In Zhejiang Province, China, limited research has been conducted recently on the awareness of TB in schools among college students. Therefore, this study aims to gain insight into TB knowledge among low-grade college students in Zhejiang Province and develop effective strategies for TB education targeted at this specific population. Methods: A cross-sectional survey was conducted between 1st and 20th May 2022 in 20 colleges in Zhejiang Province, southeastern China. The survey aimed to assess the level of TB awareness among 1st and 2nd-year college students. Chi-square tests were performed to compare the rates, while multivariate logistic regression was used to identify the factors influencing the overall awareness level of students' regarding key knowledge about TB. Results: A total of 4,414 lower-grade students participated in the study. The total awareness rate and entire awareness rate of key TB knowledge were 81.6 and 25.3%, respectively. Participants who demonstrated a relatively poor understanding of the definition were (51.0%), curable outcomes (75.7%), and preventive measures of TB (76.1%). Female participants [adjusted odds ratio (aOR):1.44; 95% confidence interval (CI):1.25-1.65], medical students (aOR:2.00; 95%CI:1.63-2.64), had a high level of monthly expenditures (aOR:2.50; 95%CI:1.49-4.19), had prior TB health education (aOR:1.95; 95%CI:1.68-2.25) and previous exposure to TB patients (aOR:2.13; 95% CI:1.48-3.08) indicating a better level of awareness of key knowledge about TB. Among the students, 58.5% expressed their willingness to acquire TB knowledge through "broadcasting, television, films, and audiovisual materials." Conclusions: The total awareness rate of key knowledge among low-grade college students in Zhejiang did not meet the national requirements. To effectively prevent TB in schools, it is crucial to develop a comprehensive understanding of the disease among college students. Therefore, it is necessary to enhance TB awareness through theoretical and practical education, starting from the early semesters of college.

Atomically precise photothermal nanomachines.

Interfacing molecular machines to inorganic nanoparticles can, in principle, lead to hybrid nanomachines with extended functions. Here we demonstrate a ligand engineering approach to develop atomically precise hybrid nanomachines by interfacing gold nanoclusters with tetraphenylethylene molecular rotors. When gold nanoclusters are irradiated with near-infrared light, the rotation of surface-decorated tetraphenylethylene moieties actively dissipates the absorbed energy to sustain the photothermal nanomachine with an intact structure and steady efficiency. Solid-state nuclear magnetic resonance and femtosecond transient absorption spectroscopy reveal that the photogenerated hot electrons are rapidly cooled down within picoseconds via electron-phonon coupling in the nanomachine. We find that the nanomachine remains structurally and functionally intact in mammalian cells and in vivo. A single dose of near-infrared irradiation can effectively ablate tumours without recurrence in tumour-bearing mice, which shows promise in the development of nanomachine-based theranostics.

Bimolecularly passivated interface enables efficient and stable inverted perovskite solar cells.

Compared with the n-i-p structure, inverted (p-i-n) perovskite solar cells (PSCs) promise increased operating stability, but these photovoltaic cells often exhibit lower power conversion efficiencies (PCEs) because of nonradiative recombination losses, particularly at the perovskite/C60 interface. We passivated surface defects and enabled reflection of minority carriers from the interface into the bulk using two types of functional molecules. We used sulfur-modified methylthio molecules to passivate surface defects and suppress recombination through strong coordination and hydrogen bonding, along with diammonium molecules to repel minority carriers and reduce contact-induced interface recombination achieved through field-effect passivation. This approach led to a fivefold longer carrier lifetime and one-third the photoluminescence quantum yield loss and enabled a certified quasi-steady-state PCE of 25.1% for inverted PSCs with stable operation at 65°C for >2000 hours in ambient air. We also fabricated monolithic all-perovskite tandem solar cells with 28.1% PCE.

Mechanisms of resveratrol against diabetic wound by network pharmacology and experimental validation.

BACKGROUND: Resveratrol (RSV) that possesses anti-oxidative, anti-inflammatory, and pro-angiogenic effects is an effective drug for diabetic wound (DW), while its pharmacological mechanism remains to be elucidated. In this study, we apply network pharmacology and experimental validation approach to reveal the potential mechanism of RSV against DW. METHODS: We obtained potential targets for RSV and DW from the publicly available database. Using interaction networks and conducting GO and KEGG pathway enrichment analyses, we constructed target-pathway networks to explore the relationship between RSV and DW. To validate the pharmacological mechanism of RSV, we induced the DW model. RESULTS: Ninety overlapped targets between RSV and DW were obtained, and the hub genes of the PPI network included TNF, IL-6, CASP3, MAPK3, VEGFA, IL-1ß, AKT1, and JUN. Based on target-pathway networks, the AGE-RAGE signalling pathway was involved in the RSV treatment of DW. Furthermore, in vivo experiments revealed that RSV significantly promoted wound healing in diabetic mice and attenuated the expression of pro-inflammatory cytokines in wound tissue. Meanwhile, RSV could inhibit the AGE-RAGE signalling pathway and thus reduce the activation of NF-κB. CONCLUSION: This study initially revealed the biological mechanism of RSV for treating DW through multi-target and multi-pathway. AGE-RAGE, FoxO, MAPK, PI3K-AKT and other signalling pathways may be the main pathways of RSV in treating DW. RSV reduces the inflammatory response by inhibiting the AGE-RAGE signalling pathway, which in turn promotes DW healing.

Impact of paravertebral block on perioperative neurocognitive disorder: a systematic review and meta-analysis of randomized controlled trials.

Objective: To investigate whether paravertebral block reduces postoperative delirium (POD)/delayed neurocognitive recovery (DNR) in adults after major surgery with general anesthesia. Methods: For this systematic review and meta-analysis, we searched online databases PubMed, EMBASE, CENTRAL, and Web of Science till March 19th, 2023 to examine studies which use paravertebral block (PVB) for perioperative neurocognitive disorder. Primary and secondary outcomes were identified for the incidence of perioperative neurocognitive disorder. We did not restrict the follow-up duration of the included studies. Statistical analysis was performed to calculate mean difference (MD), Odd ratios (OR) and CI between RCTs. The quality of the evidence was assessed with the Cochrane risk of bias tool. The registration number of the study in PROSPERO is CRD42023409502. PROSPERO is an international database of prospectively registered systematic reviews. Registration provides transparency in the review process and it helps counter publication bias. Results: Total 1,225 patients from 9 RCTs were analyzed. The incidence of POD [Odds Ratio (OR) = 0.48, 95% CI 0.32, 0.72; p = 0.0004; I2 = 0%] and DNR [OR = 0.32, 95% CI 0.13, 0.80; p = 0.01; I2 = 0%] were significantly reduced in PVB group. The analysis showed no significant differences in postoperative MMSE scores [MD = 0.50, 95% CI -2.14, 3.15; p = 0.71; I2 = 98%]. Paravertebral block analgesia reduces pain scores and/or opioid use after surgery. Additionally, blood pressure was significantly lower in the PVB group, intraoperatively [MD = -15.50, 95% CI -20.71, -10.28; p < 0.001; I2 = 12%] and postoperatively [MD = -5.34, 95% CI -10.65, -0.03 p = 0.05; I2 = 36%]. Finally, PVB group had significantly shorter hospital stays [MD = -0.86, 95% CI -1.13, -0.59; p < 0.001; I2 = 0%]. Conclusion: Paravertebral block analgesia may prevent perioperative POD/DNR in patients undergoing major surgery. Further research with large sample sizes is required to confirm its effectiveness.

Ultrasound-targeted semaglutide-loaded PEG-nanoliposomes microbubble destruction protects diabetic cardiomyopathy by activating PI3K/Akt/Nrf2 signaling pathway.

Objective: To investigate the ameliorative effect of Semaglutide-loaded PEG-nanoliposomes (Sem-PEG-lips) combined with ultrasound-targeted microbubble destruction (UTMD) on streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM) in rodents and its potential mechanisms. Methods: Sem-PEG-lips were prepared by the reverse phase evaporation method. Fifty STZ-induced diabetic rats were randomly divided into DCM model group, Sem or Sem-PEG-lips alone treatment group, UTMD + Sem group and UTMD + Sem-PEG-lips group (n = 10), respectively, and used the healthy rats as normal control. During the 12-week intervention, the weight and blood glucose levels of all rats were recorded. Myocardial injury and fibrosis were observed by using H&E and Masson staining. The activity of antioxidant enzymes and the expression levels of oxidative stress-related signaling pathway markers in myocardial tissues were measured by ELISA and western blotting method, respectively. Results: Compared with DCM rats, the body weight and blood glucose levels of those in the UTMD + Sem-PEG-lips group were significantly increased and decreased, respectively (both p < 0.05). The results of H&E and Masson staining showed that myocardial fibrosis and apoptosis were both significantly improved in combination group (both p < 0.001). Further results of ELISA and Western blot analysis showed that the activity of antioxidant enzymes in ones received combination therapy were significantly higher than that in DCM model group (all p < 0.001), and the expression of PI3K/Akt/Nrf2 signaling pathway related proteins were significantly up-regulated (all p < 0.001), and all these changes were reversed by the treatment of PI3K inhibitor. results. Conclusion: UTMD combined Sem-PEG-lips can reduce the oxidative stress of myocardial tissue in DCM rats by activating PI3K/Akt/Nrf2 signaling pathway, thereby improving diabetic myocardial injury.