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Abstract Temozolomide (TMZ) is widely utilized as the primary chemotherapeutic intervention for glioblastoma. However, the clinical use of TMZ is limited by its various side effects and resistance to chemotherapy. The present study revealed the synergistic inhibition of glioblastoma through the combined administration of TMZ and perifosine. This combination therapy markedly diminished BRCA1 expression, resulting in the suppression of DNA repair mechanisms. Furthermore, the combination of TMZ and perifosine elicited caspase-dependent apoptosis, decreasing glioblastoma cell viability and proliferation. The observed synergistic effect of this combination therapy on glioblastoma was validated in vivo, as evidenced by the substantial reduction in glioblastoma xenograft growth following combined treatment with TMZ and perifosine. In recurrent glioma patients, higher BRCA1 expression is associated with worse prognosis, especially the ones that received TMZ-treated. These findings underscore the potent antitumor activity of the AKT inhibitor perifosine when combined with TMZ and suggest that this approach is a promising strategy for clinical glioblastoma treatment.

Abstract Background Immune-positron emission tomography (PET) imaging with tracers that target CD8 and granzyme B has shown promise in predicting the therapeutic response following immune checkpoint blockade (ICB) in immunologically “hot” tumors. However, immune dynamics in the low T-cell infiltrating “cold” tumor immune microenvironment during ICB remain poorly understood. This study uses molecular imaging to evaluate changes in CD4 + T cells and CD8 + T cells during ICB in breast cancer models and examines biomarkers of response. Methods [89Zr]Zr-DFO-CD4 and [89Zr]Zr-DFO-CD8 radiotracers were used to quantify changes in intratumoral and splenic CD4 T cells and CD8 T cells in response to ICB treatment in 4T1 and MMTV-HER2 mouse models, which represent immunologically “cold” tumors. A correlation between PET quantification metrics and long-term anti-tumor response was observed. Further biological validation was obtained by autoradiography and immunofluorescence. Results Following ICB treatment, an increase in the CD8-specific PET signal was observed within 6 days, and an increase in the CD4-specific PET signal was observed within 2 days in tumors that eventually responded to immunotherapy, while no significant differences in CD4 or CD8 were found at the baseline of treatment that differentiated responders from nonresponders. Furthermore, mice whose tumors responded to ICB had a lower CD8 PET signal in the spleen and a higher CD4 PET signal in the spleen compared to non-responders. Intratumoral spatial heterogeneity of the CD8 and CD4-specific PET signals was lower in responders compared to non-responders. Finally, PET imaging, autoradiography, and immunofluorescence signals were correlated when comparing in vivo imaging to ex vivo validations. Conclusions CD4- and CD8-specific immuno-PET imaging can be used to characterize the in vivo distribution of CD4 + and CD8 + T cells in response to immune checkpoint blockade. Imaging metrics that describe the overall levels and distribution of CD8 + T cells and CD4 + T cells can provide insight into immunological alterations, predict biomarkers of response to immunotherapy, and guide clinical decision-making in those tumors where the kinetics of the response differ.

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder with no effective treatments available. There is growing evidence that cuproptosis contributes to the pathogenesis of this disease. This study developed a novel molecular clustering based on cuproptosis-related genes and constructed a signature for AD patients.MethodsThe differentially expressed cuproptosis-related genes (DECRGs) were identified using the DESeq2 R package. The GSEA, PPI network, GO, KEGG, and correlation analysis were conducted to explore the biological functions of DECRGs. Molecular clusters were performed using unsupervised cluster analysis. Differences in biological processes between clusters were evaluated by GSVA and immune infiltration analysis. The optimal model was constructed by WGCNA and machine learning techniques. Decision curve analysis, calibration curves, receiver operating characteristic (ROC) curves, and two additional datasets were employed to confirm the prediction results. Finally, immunofluorescence (IF) staining in AD mice models was used to verify the expression levels of risk genes.ResultsGSEA and CIBERSORT showed higher levels of resting NK cells, M2 macrophages, naïve CD4+ T cells, neutrophils, monocytes, and plasma cells in AD samples compared to controls. We classified 310 AD patients into two molecular clusters with distinct expression profiles and different immunological characteristics. The C1 subtype showed higher abundance of cuproptosis-related genes, with higher proportions of regulatory T cells, CD8+T cells, and resting dendritic cells. We subsequently constructed a diagnostic model which was confirmed by nomogram, calibration, and decision curve analysis. The values of area under the curves (AUC) were 0.738 and 0.931 for the external datasets, respectively. The expression levels of risk genes were further validated in mouse brain samples.ConclusionOur study provided potential targets for AD treatment, developed a promising gene signature, and offered novel insights for exploring the pathogenesis of AD.

Under the leadership of the Communist Party of China (CPC), this study aims to explore the relationship between independent directors who are CPC members and firms' ESG (environmental, social, and governance) performance. We use a sample of 30,629 A-share firms in China for the period 2012–2021. Our main results show that CPC membership among independent directors can significantly improve firms' ESG performance, with board meetings serving as an important mechanism for this effect. We also examine the impact of CPC membership on external supervision, attention levels, “full and strict governance over the Party”, and ownership nature. The influence of independent directors' CPC membership on firms' ESG performance is greater in companies lacking external supervision, those with higher attention levels, and in state-owned enterprises (SOEs).

Abstract Background Hyperuricemia and low level of high-density lipoprotein cholesterol (HDL-C) are both risk factors for coronary artery disease (CAD). The uric acid to HDL-C ratio (UHR) has recently been identified as a new inflammatory and metabolic biomarker. However, the relationship between the UHR and coronary culprit plaques has not been fully investigated in patients with acute coronary syndrome (ACS). Methods A total of 346 patients with ACS were enrolled in this study. Culprit lesion characteristics were assessed by optical coherence tomography (OCT). Logistic regression and linear correlation analyses were performed to assess the association between the UHR and culprit plaques. The predictive value of the UHR was investigated by receiver operating characteristic (ROC) curve analysis. Results The percentages of typical culprit plaques, including ruptures, erosions and thrombi, were greater in the high-UHR subgroup than those in the low-UHR subgroup. A positive relationship was also found between the UHR and diameter stenosis (r = 0.160, P = 0.003) and between the UHR and area stenosis (r = 0.145, P = 0.007). The UHR was found to be independently associated with plaque rupture, erosion and thrombus. Furthermore, ROC analysis suggested that the UHR had a better predictive value than low-density lipoprotein cholesterol. Conclusions An elevated UHR level was independently related to the occurrence rate of culprit plaques. The UHR is a simple and easily acquired parameter for detecting culprit plaques in patients with ACS.

ABSTRACTOff-target biodistribution of biologics bears important toxicological consequences. Antibody fragments intended for use as vectors of cytotoxic payloads (e.g. antibody-drug conjugates, radiotherapy) can accumulate at clearance organs like kidneys and liver, where they can cause dose-limiting toxicities. Renal and hepatic uptakes are known to be affected by protein electrostatics, which promote protein internalization through pinocytosis. Using minibodies as a model of an antibody fragment lacking FcRn recycling, we compared the biodistributions of leads with different degrees of accumulation at the kidney and liver. We identified a positive electrostatic patch highly conserved in a germline family very commonly used in the humanization of approved biologics. Neutralization of this patch led to a drastic reduction in the kidney uptake, leading to a biodistribution more favorable to the delivery of highly cytotoxic payloads. Next, we conducted a high throughput study of the electrostatic properties for all combinations of VH and VL germlines. This analysis shows how different VH/VL combinations exhibit varying tendencies to create electrostatic patches, resulting in Fv variants with different isoelectric points. Our work emphasizes the importance of carefully selecting germlines for humanization with optimal electrostatic properties in order to control the unspecific tissue uptake of low molecular weight biologics.

Much research describes gut microbiota in atherosclerotic cardiovascular diseases (ASCVD) for that the composition of the intestinal microbiome or its metabolites can directly participate in the development of endothelial dysfunction, atherosclerosis and its adverse complications. Salidroside, a natural phenylpropane glycoside, exhibits promising biological activity against the progression of ASCVD. Recent studies suggested that the gut microbiota played a crucial role in mediating the diverse beneficial effects of salidroside on health. Here, we describe the protective effects of salidroside against the progression of atherosclerosis. Salidroside regulates the abundance of gut microbiotas and gut microbe-dependent metabolites. Moreover, salidroside improves intestinal barrier function and maintains intestinal epithelial barrier function integrity. In addition, salidroside attenuates the inflammatory responses exacerbated by gut microbiota disturbance. This review delves into how salidroside functions to ameliorate atherosclerosis by focusing on its interaction with gut microbiota, uncovering the potential roles of gut microbiota in the diverse biological impacts of salidroside.

BackgroundHypertrophic Cardiomyopathy (HCM), a widespread genetic heart disorder, is largely associated with sudden cardiac fatality. Necroptosis, an emerging type of programmed cell death, plays a fundamental role in several cardiovascular diseases.AimThis research utilized bioinformatics analysis to investigate necroptosis's implication in HCM.MethodsThe study retrieved RNA sequencing datasets GSE130036 and GSE141910 from the Gene Expression Omnibus (GEO) database. It detected necroptosis-linked differentially expressed genes (NRDEGs) by reviewing both the gene set for necroptosis and the differently expressed genes (DEGs). The enriched signaling pathway of HCM was assessed using GSEA, while common DEGs were studied through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Concurrently, the Protein-Protein Interaction network (PPI) proved useful for identifying central genes. CIBERSORT facilitated evaluating the correlation between distinct immune cell-type prevalence and NRDEGs by analyzing immune infiltration patterns. Lastly, GSE141910 dataset validated the expression ranks of NRDEGs and immune-cell penetration.ResultsThe investigation disclosed significant enrichment and activation of the necroptosis pathway in HCM specimens. Seventeen diverse genes, including CYBB, BCL2, and JAK2 among others, were identified in the process. PPI network scrutiny classified nine of these genes as central genes. Results from GO and KEGG enrichment analyses showed substantial connections of these genes to pathways pertaining to the HIF-1 signaling track, necroptosis, and NOD-like receptor signaling process. Moreover, an imbalance in M2 macrophage cells in HCM samples was observed. Finally, CYBB, BCL2, and JAK2 emerged as vital genes and were validated using the GSE141910 dataset.ConclusionThese results indicate necroptosis as a probable underlying factor in HCM, with immune cell infiltration playing a part. Additionally, CYBB, BCL2, JAK2 could act as potential biomarkers for recognizing HCM. This information forms crucial insights into the basic mechanisms of HCM and could enhance its diagnosis and management.

IntroductionGlioma is the most common primary intracranial neoplasm with a relatively poor prognosis.Case presentationHere, we present a unique case of a 53-year-old woman with two histopathologically distinct gliomas at the initial diagnosis. She presented with headaches and left limb weakness before admission, and magnetic resonance imaging (MRI) showed right frontal and basal ganglia area involvement combined with hemorrhage. The patient underwent a navigation-guided craniotomy for tumor removal. Pathological examination revealed the right frontal lobe lesion as a WHO grade II IDH-NOS astrocytoma, but the right parietal lobe lesion was a WHO grade IV IDH-mutant diffuse astrocytoma. Molecular detection of the parietal lesion revealed a point mutation at the R132 locus of the IDH1 gene, no mutation in the TERT promoter, amplification of the epidermal growth factor receptor, and a non-homozygous CDKN2A/B deletion.DiscussionIn-depth epigenomic analysis and molecular examination revealed that one patient had two different brain tumors, underscoring the importance of performing a comprehensive brain tumor workup.ConclusionThis unique case confirms that adjacent astrocytomas may have different molecular pathogenesis and provides novel insights into the development of gliomas.

Abstract Background Acute ischemic stroke (AIS) is one of the leading contributors to death and disability in adults. And cuproptosis is a novel type of cell death. Yet, its role in AIS is still unknown. Methods The mRNA, miRNA, and circRNA expression data were downloaded from the Gene Expression Omnibus database. We explored differentially expressed circRNAs (DEcircRNAs), microRNAs (DEmiRNAs), and cuproptosis-related genes (DECuRGs) after AIS. With the target prediction tools, we constructed a cuproptosis-related competitive endogenous RNA (ceRNA) network mediated by circRNAs in AIS. Afterward, functional enrichment analysis, cytoHubba plugin, protein–protein interaction, weighted gene co-expression network analysis, and unsupervised clustering analysis were performed to determine the critical genes and relevant pathways. Machine learning techniques were used to identify the optimal risk model. The CIBERSORT was applied to explore the immune-infiltrating characteristics in AIS samples. Finally, two independent datasets were employed to verify the predictive value of the risk model. Results Altogether, 26 DECuRGs were identified in this study. Enrichment analysis revealed that they participated in the reactive oxygen metabolism, inflammatory responses, and corresponding cuproptosis-related biological processes. Of the DECuRGs, MTF1 and UBE2D2 were included in the ceRNA network, comprising three circRNA-miRNA and two miRNA-mRNA interaction pairs. Hub gene analysis determined the hub regulatory axis in the process of cuproptosis, namely, MTF1-miR-765-circ_0040760/0068531. We finally constructed a 5-gene risk model (C10orf32, NUCB1, AX748267, MRPL28, and PPP1R15A) by multiple analyses, which was validated by two independent datasets (AUC = 0.958 and 0.668). Besides, significant differences in immune cell infiltration were observed between AIS patients and normal controls. The levels of neutrophils were correlated with most of the DECuRGs. The ceRNA axis identified in this study was also associated with the immune microenvironment of AIS patients. Conclusion The findings revealed that cuproptosis might be associated with AIS and that the key nodes, including the regulatory axes, might exert critical roles in the process of AIS. The risk model provided new insights into the early diagnosis and treatment of AIS.

Objective: To design new and effective polyphenol oxidase （PPO） inhibitors and expand their application in the field of aquatic product preservation. Methods: The synthesized H8[P2Mo17Ni（OH2）O61] （P2Mo17Ni） structure was characterized by ultraviolet and infrared spectrum. The inhibitory effect, type and mechanism of P2Mo17Ni on the relative activity of mushroom PPO in vitro was clarified. Then, the preservation effects of P2Mo17Ni on Litopenaeus vannamei Boone were evaluated through studying the index change of shrimps treated with P2Mo17Ni stored at 4 ℃, in which included the sensory score, the value of chromatic aberration L*, the value of total chromatic aberration （ΔE）, the total number of colonies, the value of pH and the value of total volatile basic nitrogen （TVB-N）. Results: The results showed that P2Mo17Ni was synthesized successfully. P2Mo17Ni inhibited the activity of PPO from mushroom in vitro with semi-inhibitory concentration （IC50） of （0.377±0.004） mmol/L. P2Mo17Ni inhibited mushroom PPO in a competitive reversible manner, and the inhibition constant KI was 0.185 mmol/L. Under the cold storage condition of 4 ℃, compared with the control group, P2Mo17Ni could effectively delay the decline of sensory score and the increase of L* and ΔE value in shrimps treated with P2Mo17Ni, and the inhibitory effect was significant. P2Mo17Ni could significantly inhibit the increase of total number of colonies, pH value and TVB-N value. P2Mo17Ni could extend the shelf life of shrimps for 4~5 days. Conclusion: P2Mo17Ni can slow down the blackening of shrimps and prevent its spoilage. P2Mo17Ni possesses a good preservation effect on L. vannamei and can be used in the preservation industry of aquatic products.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with a high degree of malignancy and poor prognosis. Tumor-associated macrophages (TAMs) have been identified as significant contributors to the growth and metastasis of TNBC through the secretion of various growth factors and chemokines. Salvianolic acid A (SAA) has been shown to have anti-cancer activities. However, the potential activity of SAA on re-polarized TAMs remains unclear. As there is a correlation between the TAMs and TNBC, this study investigates the effect of SAA on TAMs in the TNBC microenvironment. For that purpose, M2 TAM polarization was induced by two kinds of TNBC-conditioned medium (TNBC-TCM) in the absence or presence of SAA. The gene and protein expression of TAM markers were analyzed by qPCR, FCM, IF, ELISA, and Western blot. The protein expression levels of ERK and p-ERK in M2-like TAMs were analyzed by Western blot. The migration and invasion properties of M2-like TAMs were analyzed by Transwell assays. Here, we demonstrated that SAA increased the expression levels of CD86, IL-1β, and iNOS in M2-like TAMs and, conversely, decreased the expression levels of Arg-1 and CD206. Moreover, SAA inhibited the migration and invasion properties of M2-like TAMs effectively and decreased the protein expression of TGF-β1 and p-ERK in a concentration-dependent manner, as well as TGF-β1 gene expression and secretion. Our current findings for the first time demonstrated that SAA inhibits macrophage polarization to M2-like TAMs by inhibiting the ERK pathway and promotes M2-like TAM re-polarization to the M1 TAMs, which may exert its anti-tumor effect by regulating M1/M2 TAM polarization. These findings highlight SAA as a potential regulator of M2 TAMs and the possibility of utilizing SAA to reprogram M2 TAMs offers promising insights for the clinical management of TNBC.

Quantum key distribution with continuous-variable (CVQKD) provides an alternative way for the security improvement of underwater optical communication, but facing into the awkward situation of short distance. For this reason, here we exploit photon addition operation at the emitter into enhancing the performance of underwater CVQKD. Based on numerical simulation, it is shown that applying photon-addition non-Gaussian operation between entangled resource and the sender can further enhance both the secure key rate and the transmission distance, compared to apply photon subtraction operation between entangled resource and the receiver. In addition, the influence of seawater quality factors in underwater CVQKD system is also considered, so as to provide technical support for underwater safety communication.

BackgroundSpinal meningioma is a common intraspinal tumor, which mainly occurs in the thoracic spine. Ossified meningioma (OSM) is an extremely rare histological variant. Our article reports a rare patient with dorsal complete OSM and reviews this subject.Case presentationA 68-year-old woman presented with a one-year history of progressive weakness in both lower limbs with gait disturbance. Physical examination revealed hypoesthesia with a sensory level below T10. Babinski and pathological signs on both sides were weakly positive. Magnetic resonance imaging (MRI) showed a mass at the T10 to T11 level causing severe compression of the spinal cord. Computed tomography (CT) showed complete ossification of the mass. 18F-Fluoro-deoxy-glucose positron emission tomography CT (18F-FDG PET/CT) scan combined with MRI revealed that the mass was an intradural extramedullary high-density ossified nodule. The patient underwent a gross total resection of the mass and pathologic examination indicated that the mass was a meningioma with diffused psammomatous bodies.ConclusionWe identified a rare case of dorsal complete OSM occurring in a 68-year-old woman. After complete surgical resection, although there were complications such as cerebral fluid leakage and fever, the patient finally recovered with a satisfactory result.

Abstract Background The effect of neuroinflammatory cytokines on cognitive deficits in patients with major depressive disorder (MDD) can be altered by selective serotonin reuptake inhibitors (SSRIs). This study aimed to examine serum interleukin-8 (IL-8) levels, cognitive function, and their associations in MDD patients with SSRIs. Methods Thirty SSRI-treated MDD patients and 101 healthy controls were recruited for this study. We examined cognitive performance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-8 levels using the Human Inflammatory Cytokine Cytometric Bead Array in both cases and controls. Results The RBANS test scores were significantly lower in MDD patients with SSRIs than in healthy controls after controlling for covariates (all p

Abstract Background The circular RNA (circRNA) plays a vital role in the pathogenesis of tumors as a competitive endogenous RNA (ceRNA). Given the high aggressiveness and fatality rate of glioblastoma (GBM) as well as poor prognosis, it is necessary to construct a circRNA-related ceRNA network for further studies on the mechanism of GBM and identify possible biomarkers as well as therapeutic drugs. Methods Three datasets from the gene expression omnibus (GEO) database were downloaded to distinguish differential circRNAs, microRNAs, and messenger RNAs respectively in GBM. With the help of GEPIA2, circBank, CSCD, TargetScan, miRDB, and miRTarBase databases, we established a circRNAs-related ceRNA network in GBM. Functional enrichments were employed to profile the most relevant mRNAs to indirectly clarify the mechanisms of the ceRNA network. Based on the expression profile data and survival information of GBM patients from the GEO and the cancer genome atlas (TCGA) databases, we performed survival analysis to select prognostic mRNAs and constructed a novel circRNA-miRNA-mRNA central regulatory subnetwork. The DGIdb database was used to find potential drug–gene interactions. Results The datasets obtained from the GEO and TCGA databases were analyzed, and 504 differentially expressed mRNAs (DEmRNAs), 71 differentially expressed microRNAs (DEmiRNAs), and 270 differentially expressed circRNAs (DEcircRNAs) were screened out. The novel ceRNA regulatory network included 22 circRNAs, 11 miRNAs, and 15 mRNAs. FZD1 and KLF10 were significantly correlated with the overall survival rate of patients with GBM (P

Abstract The protective arm of the renin-angiotensin system (RAS), the ACE 2/Ang-(1–7)/MasR axis, has become a new anti-inflammatory target. As a specific activator of ACE2, diminazene aceturate (DA) can promote anti-inflammatory effects by regulating the ACE2/Ang-(1–7)/MasR axis. However, due to the reported toxicity of DA, its application has been limited. In the current study, we synthesized a low toxicity DA derivative 3 (DAD3) and sought to determine whether DAD3 can also activate ACE2 in bovine mammary epithelial cells (BMEC) and regulate the RAS system to inhibit inflammation. We found that both DA and DAD3 can activate and promote ACE2 expression in BMEC. iRNA-mediated knockdown of ACE2 demonstrated that DAD3 activates the ACE2/Ang-(1–7)/MasR axis and plays an anti-inflammatory role in BMEC. Furthermore, the inhibitory effects of DA and DAD3 on the protein phosphorylation of MAPK and NF-κB pathways were reduced in ACE2-silenced BMEC. Our findings show that ACE2 is a target of DAD3, which leads to inhibition of the MAPK and NF-κB signalling pathways and protects against LPS-induced inflammation in BMEC. Thus, DAD3 may provide a new strategy to treat dairy cow mastitis.

BackgroundStudies have shown that longer leukocyte telomere length (LTL) is significantly associated with increased risk of meningioma. However, there is limited evidence concerning the causal association of LTL with benign and malignant meningiomas or with the location of benign tumors.MethodsWe used three LTL datasets from different sources, designated by name and sample size as LTL-78592, LTL-9190, and LTL-472174. The linkage disequilibrium score (LDSC) was used to explore the association between LTL and meningioma. We utilized two-sample bidirectional Mendelian randomization (TSMR) to evaluate whether LTL is causally related to meningioma risk. We adjusted for confounders by conducting multivariable Mendelian randomization (MVMR).ResultsIn the LTL-78592, longer LTL was significantly associated with increased risk of malignant [odds ratio (OR) = 5.14, p = 1.04 × 10−5], benign (OR = 4.81, p

Many bacterial pathogens can cause septicemia and spread from the bloodstream into internal organs. During leptospirosis, individuals are infected by contact with Leptospira-containing animal urine-contaminated water. The spirochetes invade internal organs after septicemia to cause disease aggravation, but the mechanism of leptospiral excretion and spreading remains unknown. Here, we demonstrated that Leptospira interrogans entered human/mouse endothelial and epithelial cells and fibroblasts by caveolae/integrin-β1-PI3K/FAK-mediated microfilament-dependent endocytosis to form Leptospira (Lep)-vesicles that did not fuse with lysosomes. Lep-vesicles recruited Rab5/Rab11 and Sec/Exo-SNARE proteins in endocytic recycling and vesicular transport systems for intracellular transport and release by SNARE-complex/FAK-mediated microfilament/microtubule-dependent exocytosis. Both intracellular leptospires and infected cells maintained their viability. Leptospiral propagation was only observed in mouse fibroblasts. Our study revealed that L. interrogans utilizes endocytic recycling and vesicular transport systems for transcytosis across endothelial or epithelial barrier in blood vessels or renal tubules, which contributes to spreading in vivo and transmission of leptospirosis.

As an important part of the International Health Regulations, risk communication plays a significant role in the response and management of public health emergencies. Recommended by World Health Organization (WHO), the five principles for risk communication practice include building trust，releasing information timely，information transparency，paying attention to the public, and formulating preplan. In the study, we analyze and summarize the application of WHO′s five principles of risk communication in the management process of a health emergency response after a strong earthquake occurred in Maduo County, Guoluo Tibetan Autonomous Prefecture, Qinghai Province in May 2021 for providing a reference to prospective practice in future.

Abstract Different surface micromorphologies influence osteoblast movements and impact the osteogenesis around implants. In this study, a biomimetic chip that simulates the microenvironment of the implant and bone in vitro was developed (tissue-on-chip of group T and group C) to study the correlation of cell movement velocity (CMV), direction (CMD), acceleration (CMA), and cell attachment number (CA) with the surface micromorphology of the Titanium material. Computational fluid dynamics (CFD) was used for flow analysis. Changes in intraosseous pressure (IOP), local blood perfusion index (LBPI), new bone microstructure, microvessel density (MVD), and bone-implant contact (BIC) in beagle dogs were detected as implant surface alterations. Surface skewness (Ssk) and surface arithmetic mean height (Sa) were the most important negative factors for high CMV, accounting for 51% and 32%, respectively, of all the influencing factors. Higher Ssk (Ssk T > 0, Ssk C Sa C ) resulted in lower CMV (CMVT:CMV C = 0.41:1), greater CA (CAT:CAC = 1.44:1), and higher BIC (BICT:BICC = 3.06:1) (P 0.05).

The characteristics and related mechanisms of the interannual variability of late summer (August) extreme precipitation in West China (WC) were investigated from 1961 to 2021. Precipitation and extreme precipitation (defined as the 99th percentile) generally decreased in the southeast-northwest direction, with a maximum in the Sichuan Basin. The non-linear trends in extreme precipitation have increased since the 1980s. Therefore, we further found that the interannual increase in extreme precipitation in the WC was significantly related to the eastward-strengthened South Asian high, western-stretched Western Pacific Subtropical high, enhanced westerly jet, anomalous cyclone in Mongolia, and anomalous anticyclone in the western Pacific. The anti-cyclonic anomaly is a Gill-type response to increase the sea surface temperature in the western Pacific. A mid-high latitude barotropic Rossby-wave train can be induced and has essential effects on the above key circulation patterns, further cooperating with the strong updrafts rather than strengthening and maintaining extreme precipitation in the WC.