Integrated analysis of facial microbiome and skin physio-optical properties unveils cutotype-dependent aging effects.

BACKGROUND: Our facial skin hosts millions of microorganisms, primarily bacteria, crucial for skin health by maintaining the physical barrier, modulating immune response, and metabolizing bioactive materials. Aging significantly influences the composition and function of the facial microbiome, impacting skin immunity, hydration, and inflammation, highlighting potential avenues for interventions targeting aging-related facial microbes amidst changes in skin physiological properties. RESULTS: We conducted a multi-center and deep sequencing survey to investigate the intricate interplay of aging, skin physio-optical conditions, and facial microbiome. Leveraging a newly-generated dataset of 2737 species-level metagenome-assembled genomes (MAGs), our integrative analysis highlighted aging as the primary driver, influencing both facial microbiome composition and key skin characteristics, including moisture, sebum production, gloss, pH, elasticity, and sensitivity. Further mediation analysis revealed that skin characteristics significantly impacted the microbiome, mostly as a mediator of aging. Utilizing this dataset, we uncovered two consistent cutotypes across sampling cities and identified aging-related microbial MAGs. Additionally, a Facial Aging Index (FAI) was formulated based on the microbiome, uncovering the cutotype-dependent effects of unhealthy lifestyles on skin aging. Finally, we distinguished aging related microbial pathways influenced by lifestyles with cutotype-dependent effect. CONCLUSIONS: Together, our findings emphasize aging's central role in facial microbiome dynamics, and support personalized skin microbiome interventions by targeting lifestyle, skin properties, and aging-related microbial factors. Video Abstract.

Mitochondrial Dysfunction-Evoked DHODH Acetylation is Involved in Renal Cell Ferroptosis during Cisplatin-Induced Acute Kidney Injury.

Several studies have observed renal cell ferroptosis during cisplatin-induced acute kidney injury (AKI). However, the mechanism is not completely clear. In this study, oxidized arachidonic acid (AA) metabolites are increased in cisplatin-treated HK-2 cells. Targeted metabolomics showed that the end product of pyrimidine biosynthesis is decreased and the initiating substrate of pyrimidine biosynthesis is increased in cisplatin-treated mouse kidneys. Mitochondrial DHODH, a key enzyme for pyrimidine synthesis, and its downstream product CoQH2, are downregulated. DHODH overexpression attenuated but DHODH silence exacerbated cisplatin-induced CoQH2 depletion and lipid peroxidation. Mechanistically, renal DHODH acetylation is elevated in cisplatin-exposed mice. Mitochondrial SIRT3 is reduced in cisplatin-treated mouse kidneys and HK-2 cells. Both in vitro SIRT3 overexpression and in vivo NMN supplementation attenuated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis. By contrast, Sirt3 knockout aggravated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis, which can not be attenuated by NMN. Additional experiments showed that cisplatin caused mitochondrial dysfunction and SIRT3 SUMOylation. Pretreatment with mitochondria-target antioxidant MitoQ alleviated cisplatin-caused mitochondrial dysfunction, SIRT3 SUMOylation, and DHODH acetylation. MitoQ pretreatment protected against cisplatin-caused AKI and renal cell ferroptosis. Taken together, these results suggest that mitochondrial dysfunction-evoked DHODH acetylation partially contributes to renal cell ferroptosis during cisplatin-induced AKI.

Systematic pharmacology and experimental validation to elucidate the inflammation-associated mechanism of Huanglian Wendan (HLWD) decoction in the treatment of MAFLD associated with atherosclerosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic-associated fatty liver disease (MAFLD) and atherosclerosis are very common disorders that frequently coexist. The therapeutic efficacy of Huanglian Wendan (HLWD) decoction, a traditional Chinese medicine (TCM) prescription, is satisfactory in treating MAFLD associated with atherosclerosis. However, the underlying mechanisms through which HLWD exerts its effects need to be elucidated. Given the complex composition of HLWD and its multiple therapeutic targets, pharmacological investigation is challenging. AIM OF THIS STUDY: This study aimed to identify the effective compounds in HLWD and elucidate the mechanisms involved in its therapeutic effect on MAFLD associated with atherosclerosis. MATERIALS AND METHODS: We used a systematic pharmacology method to identify effective compounds present in HLWD and determine the mechanism by which it affects MAFLD associated with atherosclerosis. The effective components of HLWD were identified through ultrahigh-performance liquid chromatography-q exactive-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Next, a comprehensive in silico method was used to predict potential related targets and disease targets for these compounds to establish corresponding pathways. The accuracy of our assumed systemic pharmacology results was determined by conducting follow-up experiments. RESULTS: By conducting UHPLC-Q-Orbitrap HRMS combined with network analysis, we identified 18 potentially active components of HLWD and assessed the inflammatory regulatory mechanism by which it affects MAFLD associated with atherosclerosis on the basis of 52 key targets. We used a high-fat, high-cholesterol (HFHC)-induced mice model of MAFLD associated with atherosclerosis to confirm our results. We found that administering HLWD significantly improved the appearance of their liver and reduced their body weight, liver weight, blood lipids, hepatic damage, and hepatic pathology. HLWD also decreased atherosclerotic lesion areas, foam cells, and inflammatory cells in the aorta. HLWD showed anti-inflammatory effects, suppressed M1 polarization, and promoted M2 polarization in the liver and aorta. HLWD might also regulate peroxisome proliferator-activated receptor-γ (PPARγ)/nuclear factor kappa-B (NF-κB) signaling to influence macrophage polarization and inflammation. CONCLUSIONS: Our results showed that HLWD protected against HFHC diet-induced MAFLD associated with atherosclerosis by regulating PPARγ/NF-κB signaling, thus adjusting macrophage polarization and inflammation. Additionally, pharmacochemistry research, network pharmacology analysis, and experimental verification can be combined to form a comprehensive model used in studies on TCM.

Ubiquitination of ATAD3A by TRIM25 exacerbates cerebral ischemia-reperfusion injury via regulating PINK1/Parkin signaling pathway-mediated mitophagy.

BACKGROUND: Cerebral ischemia-reperfusion injury (CI/RI) is a complex process leading to neuronal damage and death, with mitophagy implicated in its pathogenesis. However, the significance of mitophagy in CI/RI remains debated. HYPOTHESIS: We hypothesized that TRIM25 reduces ATAD3A expression by ubiquitinating ATAD3A, promoting mitochondrial autophagy via the PINK1/Parkin pathway, and aggravating CI/RI. STUDY DESIGN: Rat middle cerebral artery occlusion (MCAO) followed by reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R) in PC12 cells were used as animal and cell models, respectively. METHODS: To evaluate the success of the CI/R modeling, TTC and HE staining were employed. The determination of serum biochemical indexes was carried out using relative assay kits. The Western Blot analysis was employed to assess the expression of ATAD3A, TRIM25, as well as mitophagy-related proteins (PINK1, Parkin, P62, and LC3II/LC3I). The mRNA levels were detected using QRT-PCR. Mitochondrial membrane potential was assessed through JC-1 staining. Mitosox Red Assay Kit was utilized to measure mitochondrial reactive oxygen species levels in PC12 cells. Additionally, characterization of the mitophagy structure was performed using transmission electron microscopy (TEM). RESULTS: Our findings showed down-regulation of ATAD3A and up-regulation of TRIM25 in both in vivo and in vitro CI/RI models. Various experimental techniques such as Western Blot, JC-1 staining, Mitosox assay, Immunofluorescence assay, and TEM observation supported the occurrence of PINK1/Parkin signaling pathway-mediated mitophagy in both models. ATAD3A suppressed mitophagy, while TRIM25 promoted it during CI/RI injury. Additionally, the results indicated that TRIM25 interacted with and ubiquitinated ATAD3A via the proteasome pathway, affecting ATAD3A protein stability and expression. CONCLUSION: TRIM25 promoted Pink1/Parkin-dependent excessive mitophagy by destabilizing ATAD3A, exacerbating CI/RI. Targeting TRIM25 and ATAD3A may offer therapeutic strategies for mitigating CI/RI and associated neurological damage.

New drug combination regimen based on pharmacokinetic characteristics-Erdafitinib combined with sertraline or duloxetine.

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

Analysis of the clonal origin and differences in the biological behavior of multifocal papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) exhibits a trend of multifocal growth. However, the clonal origin of multiple cancer foci in the thyroid gland remains an issue of ongoing debate. In order to investigate the clonal origin and biological behavior differences of multifocal PTC (MPTC) from a unique perspective, a combination of dual gene and dual protein detection methods was used. The present study included 52 patients with MPTC. Immunohistochemical staining was used to assess the expression of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and telomerase reverse transcriptase (TERT) proteins, while quantitative PCR and Sanger sequencing were used to identify BRAF and TERT gene mutations. Based on the results, MPTC cases were classified into two clonal origins, namely intraglandular metastatic (71.2%) and independent multicentric origin (28.8%). BRAF protein expression and BRAF gene mutation were significantly higher in the intraglandular metastasis group than in the multicentric cancer group. However, no significant differences in TERT protein expression and TERT gene mutation were observed between the two groups. Sex, central lymph node metastasis rate, Hashimoto's thyroiditis and tumor distribution laterality were not found to differ significantly between the two groups. However, significant differences were detected in age at initial diagnosis, lateral cervical lymph node metastasis rate, tumor capsule invasion rate and maximum tumor diameter. The study found that MPTC predominantly occurs due to intraglandular metastasis, which is associated with stronger tumor invasiveness than cancer foci with multiple independent origins, as it is more likely to exhibit pathogenic gene mutations and abnormal protein expression, cervical lymph node metastasis and capsule invasion. Therefore, it is recommended that the surgical approaches and follow-up strategies for intraglandular metastatic MPTC should be aggressive and individualized.

Behavioral and economic traits reflect distinct resource acquisition strategies in tendril vines and stem twining vines.

Climbing plants are important components of tropical and many temperate forest ecosystems. Current studies regard climbing plants as a single ecological plant type and ignore the ecological differences resulting from their climbing mechanisms, which may lead to a misrepresentation of the role of climbing plants in forest dynamics. Based on behavioral traits and economic traits of climbing plants, we test the hypothesis that tendril climbers and stem twiners are characterized by different resource acquisition strategies. We quantified and compared 4 behavioral traits and 7 economic traits of four stem twining vines and four tendril vines in a temperate oak forest and further tested their differences in resource acquisition strategy. Our study found that tendril vines were scattered in a group distinct from stem twining vines along the first axes of the principal component analysis using four behavioral traits and seven economic traits, being located at the more acquisitive end with more hosts, a larger distance to length ratio of stem, higher leaf and root nitrogen concentrations, and lower leaf carbon content, while stem twining vines showed the opposite trends. These results indicate that tendril vines have a more acquisitive strategy than stem twining vines. The findings suggest a functional variability among the different climbing mechanisms, and which should be accounted for in future studies.

Noncoding RNA network crosstalk in organ fibrosis.

Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis.

Network pharmacology-based study on the mechanism of action of Trollius chinensis capsule in the treatment of upper respiratory tract infection.

BACKGROUND: Upper respiratory tract infection (URTI), one of the most common respiratory diseases, has a high annual incidence. Trollius chinensis capsule has been used to treat URTI in China. However, the underlying-mechanisms remain unclear. METHODS: Network pharmacology was used to explore the potential mechanism of action of Trollius chinensis capsule in URTI treatment. The active compounds in Trollius chinensis were obtained from the TCMSP, SymMap, and ETCM databases. The TCMSP, PubChem, and SwissTargetPrediction databases were used to predict potential targets of Trollius chinensis. URTI-associated targets were gathered from GeneCards and DisGeNET databases. The key targets and signaling pathways associated with URTI were selected by network topology, GO, and KEGG pathway enrichment analysis. Molecular docking was used to verify the binding activity between active compounds and key targets. RESULTS: Quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are major active compounds in Trollius chinensis capsule. Eighty one candidate therapeutic targets were confirmed to be involved in protection of Trollius chinensis capsule against URTI. Among them, 7 key targets (TP53, IL6, AKT1, CASP3, CXCL8, MMP9, and EGFR) were verified to have good binding affinities to the main active compounds. Furthermore, enrichment analyses suggested that inflammatory response, virus infection and oxidative stress related biological processes and pathways were possibly the potential mechanism. CONCLUSION: Overall, the present study clarified that quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are proved to be the main effective compounds of Trollius chinensis capsule treating URTI, possibly by acting on the targets of IL6, AKT1, CASP3, CXCL8, MMP9 and EGFR to play anti-infectious, anti-viral, and anti-oxidative effects. This study provides a new understanding of the active compounds and mechanisms of Trollius chinensis capsule in URTI treatment from the perspective of network pharmacology.

From immune dysregulation to organ dysfunction: understanding the enigma of Sepsis.

Sepsis is a syndrome precipitated by immune dysregulation in response to infection, and represents a pivotal factor in global mortality attributed to diseases. The recent consensus delineates sepsis as a perilous state of organ dysfunction arising from the host's maladaptive reaction to infection. It masks the complexity and breadth of the immune mechanisms involved in sepsis, which is characterized by simultaneous hyperinflammation and immunosuppression. Sepsis is highly correlated with the dysregulation of immune response, which is mainly mediated by various immune cells and their interactions. This syndrome can lead to a plethora of complications, encompassing systemic inflammatory response, metabolic disturbances, infectious shock, MODS, and DIC. Furthermore, more research studies have been conducted on sepsis in the past few years. The pathological characteristics of sepsis have been improved or treated by targeting signaling pathways like NF-B, JAK-STAT, PI3K-Akt, and p38-MAPK. Combined drug therapy is better than single drug therapy for sepsis. This article will review the latest progress in the pathogenesis and treatment of sepsis.

Pleiotropically activation of azaphilone biosynthesis by overexpressing a pathway-specific transcription factor in marine-derived Aspergillus terreus RA2905.

The genome sequencing of Aspergillus terreus reveals that the vast number of predicted biosynthetic gene clusters have not reflected by the metabolic profile observed under conventional culture conditions. In this study, a silent azaphilone biosynthetic gene cluster was activated by overexpressing a pathway-specific transcription factor gene2642 in marine-derived fungus A. terreus RA2905. Consequently, twenty azaphilone compounds were identified from the OE2642 mutant, including 11 new azaphilones and their precursors, azasperones C-J (1-5, 7-9) and preazasperones A-C (15-17). The structures of those new compounds were unambiguously determined on the basis of NMR and HRESIMS spectra analysis, and the absolute configurations were established depending on ECD calculations. Compounds 1 and 2 were the rarely reported naturally occurring azaphilones with 2-N coupled phenyl-derivative. The bioactivity assay revealed that compounds 18-20 exhibited significant anti-inflammatory activity. Based on the occurrence of diverse intermediates and the putative gene functions, a plausible biosynthetic pathway of these compounds was proposed. The above results demonstrated that overexpression of the pathway-specific transcription factor presents a promising approach for enriching fungal secondary metabolites and accelerating the targeted discovery of novel biosynthetic products.

P2RX1-Negative neutrophils promote the immunosuppressive microenvironment in Non-Small cell lung cancer by Upregulating PD-L1 expression.

BACKGROUND: The most abundant innate immune cells, neutrophils, contribute significantly to cancer development by stimulating immunosuppression. However, it remains unclear about its function and molecular mechanisms in the immunosuppressive microenvironment of non-small cell lung cancer (NSCLC). METHODS: Blood samples were collected from NSCLC patients and healthy volunteers to detect the expression of P2RX1 and PD-L1 in neutrophils using qRT-PCR, western blot (WB), and flow cytometry. Neutrophils were sorted into P2RX1-positive (P2RX1+)/P2RX1-negative (P2RX1-) groups and co-cultured with CD8+ T cells. Changes in the proliferative and cytotoxic capabilities of CD8+ T cells were then detected using flow cytometry and enzyme-linked immunosorbent assay. The content of granzyme B was determined by enzyme-linked immunosorbent assay. The effects of P2RX1-deficient neutrophils on fatty acids, triglycerides, lipid droplet content and FASN expression were detected using kits, Nile red staining and WB, respectively. RESULTS: This study revealed a deficiency in P2RX1 expression in peripheral blood neutrophils of NSCLC patients, which was negatively correlated with the expression of PD-L1. P2RX1-neutrophils inhibited T cell proliferation and granzyme B expression and promoted T cell exhaustion. Furthermore, in P2RX1-deficient neutrophils, there was a notable increase in the levels of fatty acids, triglycerides, and lipid droplet accumulation, as well as an upregulation of FASN protein expression. Mechanistically, P2RX1-neutrophils upregulated PD-L1 expression by inducing fatty acid metabolism to improve immunosuppression in NSCLC. CONCLUSION: The mechanism by which P2RX1-deficient neutrophils contributed to immunosuppressive effects in NSCLC was clarified by our findings, indicating that P2RX1 could be one potential target for counteracting the immunosuppressive effects of neutrophils.

A case report of bilateral persistent sciatic artery: Bilateral aneurysm with thromboembolism of the right lower extremity.

RATIONALE: Persistent sciatic artery (PSA) is a rare congenital vascular anomaly. The sciatic artery, which normally regresses to become the inferior gluteal artery during fetal development, persists as a direct branch of the internal iliac artery. PATIENT CONCERN: We report a 78-year-old female who was admitted due to sudden pain, numbness, and loss of sensation in the right lower limb. DIAGNOSES: Acute thromboembolism in the right leg, bilateral PSA, and bilateral aneurysm. INTERVENTIONS: After the super-selective embolization, lower limb arterial thrombolysis treatment was performed. After symptom relief, a computed tomography angiography was conducted to clarify the vascular variations. OUTCOMES: After relief of lower limb embolism, long-term antiplatelet therapy was administered. LESSONS: When performing an ultrasound examination of PSA, careful identification of the arterial anatomy, evaluation of blood flow, assessment of surrounding structures, comparison between sides, and correlation with clinical symptoms are crucial to accurately diagnose this rare vascular anomaly.

Review on ginseng and its potential active substance G-Rg2 against age-related diseases: Traditional efficacy and mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Shen Nong Herbal Classic, Ginseng (Panax ginseng C.A. Meyer) is documented to possess life-prolonging effects and is extensively utilized in traditional Chinese medicine for the treatment of various ailments such as qi deficiency, temper deficiency, insomnia, and forgetfulness. Ginseng is commonly employed for replenishing qi and nourishing blood, fortifying the body and augmenting immunity; it has demonstrated efficacy in alleviating fatigue, enhancing memory, and retarding aging. Furthermore, it exhibits a notable ameliorative impact on age-related conditions including cardiovascular diseases and neurodegenerative disorders. One of its active constituents - ginsenoside Rg2 (G-Rg2) - exhibits potential therapeutic efficacy in addressing these ailments. AIM OF THE REVIEW: The aim of this review is to explore the traditional efficacy of ginseng in anti-aging diseases and the modern pharmacological mechanism of its potential active substance G-Rg2, in order to provide strong theoretical support for further elucidating the mechanism of its anti-aging effect. METHODS: This review provides a comprehensive analysis of the traditional efficacy of ginseng and the potential mechanisms underlying the anti-age-related disease properties of G-Rg2, based on an extensive literature review up to March 12, 2024, from PubMed, Web of Science, Scopus, Cochrane, and Google Scholar databases. Potential anti-aging mechanisms of G-Rg2 were predicted using network pharmacology and molecular docking analysis techniques. RESULTS: In traditional Chinese medicine theory, ginseng has been shown to improve aging-related diseases with a variety of effects, including tonifying qi, strengthening the spleen and stomach, nourishing yin, regulating yin and yang, as well as calming the mind. Its potential active ingredient G-Rg2 has demonstrated significant therapeutic potential in age-related diseases, especially central nervous system and cardiovascular diseases. G-Rg2 exhibited a variety of pharmacological activities, including anti-apoptotic, anti-inflammatory and antioxidant effects. Meanwhile, the network pharmacological analyses and molecular docking results were consistent with the existing literature review, further validating the potential efficacy of G-Rg2 as an anti-aging agent. CONCLUSION: The review firstly explores the ameliorative effects of ginseng on a wide range of age-related diseases based on TCM theories. Secondly, the article focuses on the remarkable significance and value demonstrated by G-Rg2 in age-related cardiovascular and neurodegenerative diseases. Consequently, G-Rg2 has broad prospects for development in intervening in aging and treating age-related health problems.

Bonding Behavior and Quality of Pressureless Ag Sintering on (111)-Oriented Nanotwinned Cu Substrate in Ambient Air.

(111)-oriented nanotwinned Cu ((111)nt-Cu) has shown its high surface diffusion rate and better oxidation resistance over common polycrystalline Cu (C-Cu). The application of (111)nt-Cu as an interface metallization layer in Ag-sintered technology under the role of oxygen was investigated in this work, and its connecting behavior was further clarified by comparing it with C-Cu. As the sintering temperature decreasing from 300 to 200 °C, the shear strength on the (111)nt-Cu substrate was still greater than 55 MPa after sintering for 10 min. The fracture surface correspondingly changed from the interface of Ag/die to mixed fracture mode, involving the interface of the Ag/Cu substrate and Ag/die. The existence of copper oxide provided a tight connection between Ag and the (111)nt-Cu substrate at all of the studied temperatures. Although lots of small dispersed voids were seen at the interface between copper oxide and (111)nt-Cu at 300 °C, these impurity-induced voids would not necessarily be a failure position and could be improved by adjusting the sintering temperature and time; for example, 200 °C/10 min or heating to 300 °C, and then start cooling at the same time. The microstructure of Ag-Cu joint on (111)nt-Cu behaved better than that on C-Cu. The thinner copper oxide layer and the higher connection ratio of the interface between copper oxide and Ag were still found on the (111)nt-Cu connection's structure. The poor connection between copper oxide and Ag on C-Cu easily became the failure interface. By controlling the thickness of copper oxide and the content of impurity-induced voids, the use of (111)nt-Cu in advanced-packaging could be improved to a new level.

Deep brain stimulation and pallidotomy in primary Meige syndrome: a prospective cohort study.

BACKGROUND: Primary Meige syndrome (PMS) is a rare form of dystonia, and comparative analysis of globus pallidus internal deep brain stimulation (GPi-DBS), subthalamic nucleus deep brain stimulation (STN-DBS), and pallidotomy has been lacking. This study aims to compare the efficacy, safety, and psychiatric features of GPi-DBS, STN-DBS, and pallidotomy in patients with PMS. METHODS: This prospective cohort study was divided into three groups: GPi-DBS, STN-DBS, and pallidotomy. Clinical assessments, including motor and non-motor domains, were evaluated at baseline and at 1 year and 3 years after neurostimulation/surgery. RESULTS: Ninety-eight patients were recruited: 46 patients received GPi-DBS, 34 received STN-DBS, and 18 underwent pallidotomy. In the GPi-DBS group, the movement score of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) improved from a mean (SE) of 13.8 (1.0) before surgery to 5.0 (0.7) (95% CI, -10.5 to -7.1; P < 0.001) at 3 years. Similarly, in the STN-DBS group, the mean (SE) score improved from 13.2 (0.8) to 3.5 (0.5) (95% CI, -10.3 to -8.1; P < 0.001) at 3 years, and in the pallidotomy group, it improved from 14.9 (1.3) to 6.0 (1.1) (95% CI, -11.3 to -6.5; P < 0.001) at 3 years. They were comparable therapeutic approaches for PMS that can improve motor function and quality of life without non-motor side effects. CONCLUSIONS: DBS and pallidotomy are safe and effective treatments for PMS, and an in-depth exploration of non-motor symptoms may be a new entry point for gaining a comprehensive understanding of the pathophysiology.

[Guidelines for traditional dietary care in autumn and winter].

The National Nutrition Plan(2017-2030) and the Healthy China Action Plan(2019-2030) propose to vigorously develop traditional dietary care services, fully leverage the role of traditional dietary care in modern nutrition, and guide citizens to develop dietary habits that are in line with the dietary characteristics of different regions in China. Traditional dietary care has a long history in China and is one of the brilliant treasures of Chinese cuisine and traditional Chinese medicine(TCM) culture. It has played an important role in disease prevention, treatment, and health preservation and longevity. To promote the traditional culture of TCM, and guide and standardize the application and promotion of dietary care, it is necessary to develop a dietary care guideline with TCM characteristics. Based on the theories and practices of TCM, the China Academy of Chinese Medical Sciences(CACMS) has developed this guideline, which is tailored to local conditions and combined with modern nutrition, and targets people with different physical constitutions. According to the principles of dialectical diet, tailored to people, times, and local conditions, reinforcing healthy qi, correction, the combination of meat and vegetables, and the combination of four qi and five flavors, suitable ingredients are recommended(including TCM materials that are both food and medicinal materials). By promoting the popularization and development of traditional dietary care, this guideline contributes to integrating the strength of TCM into a unique nutritional and health model with Chinese characteristics.

[A case report of Crohn's disease in a child with trisomy 8]. / ä¼´8å·æŸ“è‰²ä½“ä¸‰ä½“çš„å„¿ç«¥å ‹ç½—æ©ç— 1例报告.

The patient is a 12-year-old male who has experienced recurrent perianal abscesses for over 10 years, along with recurrent oral ulcers and deformities in the joints of hands and feet. Gastrointestinal endoscopy and capsule endoscopy revealed multiple ulcers in the digestive tract. Combined with his histopathological examinations, the patient was diagnosed with Crohn's disease. Whole exome sequencing and peripheral blood karyotype analysis indicated a karyotype of 47,XY,+8. The patient was treated with a "step-up" strategy. His clinical symptoms were under control, with significant improvement observed during endoscopic examination. This case suggests that early-onset inflammatory bowel disease may have genetic susceptibility, and when accompanied by other multi-system involvement, the possibility of chromosomal abnormalities, such as trisomy 8, should be considered and given due attention.

Red cell distribution width/albumin ratio and mortality risk in rheumatoid arthritis patients: Insights from a NHANES study.

BACKGROUND: Despite the established negative regulatory effects observed in various diseases like cardiovascular disease and diabetes, the distinct impact of red cell distribution width (RDW) to albumin ratio (RAR) on mortality within the realm of rheumatoid arthritis (RA) remains obscure. This study sought to explore the relationship between RAR and mortality in RA patients. METHODS: A cohort of 2151 adults with RA from the National Health and Nutrition Examination Survey (NHANES) spanning 2003-2016 was analyzed for RAR levels derived from red cell distribution width and albumin concentrations. Utilizing Cox regression analysis, Kaplan-Meier curves, and Restricted Cubic Spline (RCS) models, we assessed the association between RAR levels and RA mortality while adjusting for potential confounding variables. RESULTS: Participants with higher RAR had a twofold to threefold increased risk of all-cause (HR = 3.10, 95% CI: 2.26-4.24) and cardiovascular mortality (HR = 2.46, 95%CI: 1.26-4.79) versus lower RAR. Kaplan-Meier analysis revealed that the higher RAR group had a significantly lower survival rate compared to the lower RAR group for both all-cause and cardiovascular mortality (both p < .0001), with a more pronounced effect observed for all-cause mortality. Furthermore, the RCS-fitted Cox regression model illustrated a nonlinear positive correlation between RAR levels and RA mortality. CONCLUSION: Overall, a higher RAR was associated with an increased risk mortality in RA patients. These findings underscore the potential of RAR as a prognostic biomarker in predicting outcomes in RA.