Enrichment of Nutmeg Essential Oil from Oil-in-Water Emulsions with PAN-Based Membranes.

This study used polyacrylonitrile (PAN) and heat-treated polyacrylonitrile (H-PAN) membranes to enrich nutmeg essential oils, which have more complex compositions compared with common oils. The oil rejection rate of the H-PAN membrane was higher than that of the PAN membrane for different oil concentrations of nutmeg essential oil-in-water emulsions. After heat treatment, the H-PAN membrane showed a smaller pore size, narrower pore size distribution, a rougher surface, higher hydrophilicity, and higher oleophobicity. According to the GC-MS results, the similarities of the essential oils enriched by the PAN and H-PAN membranes to those obtained by steam distillation (SD) were 0.988 and 0.990, respectively. In addition, these two membranes also exhibited higher essential oil rejection for Bupleuri Radix, Magnolia Officinalis Cortex, Caryophylli Flos, and Cinnamomi Cortex essential oil-in-water emulsions. This work could provide a reference for membrane technology for the non-destructive separation of oil with complex components from oil-in-water emulsions.

Artificial intelligence enhances whole-slide interpretation of PD-L1 CPS in triple-negative breast cancer: A multi-institutional ring study.

BACKGROUND AND AIMS: Evaluation of the programmed cell death ligand-1 (PD-L1) combined positive score (CPS) is vital to predict the efficacy of the immunotherapy in triple-negative breast cancer (TNBC), but pathologists show substantial variability in the consistency and accuracy of the interpretation. It is of great importance to establish an objective and effective method which is highly repeatable. METHODS: We proposed a model in a deep learning-based framework, which at the patch level incorporated cell analysis and tissue region analysis, followed by the whole-slide level fusion of patch results. Three rounds of ring studies (RSs) were conducted. Twenty-one pathologists of different levels from four institutions evaluated the PD-L1 CPS in TNBC specimens as continuous scores by visual assessment and our artificial intelligence (AI)-assisted method. RESULTS: In the visual assessment, the interpretation results of PD-L1 (Dako 22C3) CPS by different levels of pathologists have significant differences and showed weak consistency. Using AI-assisted interpretation, there were no significant differences between all pathologists (P = 0.43), and the intraclass correlation coefficient (ICC) value was increased from 0.618 [95% confidence interval (CI) = 0.524-0.719] to 0.931 (95% CI = 0.902-0.955). The accuracy of interpretation result is further improved to 0.919 (95% CI = 0.886-0.947). Acceptance of AI results by junior pathologists was the highest among all levels, and 80% of the AI results were accepted overall. CONCLUSION: With the help of the AI-assisted diagnostic method, different levels of pathologists achieved excellent consistency and repeatability in the interpretation of PD-L1 (Dako 22C3) CPS. Our AI-assisted diagnostic approach was proved to strengthen the consistency and repeatability in clinical practice.

Efficient generation of cloned cats with altered coat colour by editing of the KIT gene.

Coat colour largely determines the market demand for several cat breeds. The KIT proto-oncogene (KIT) gene is a key gene controlling melanoblast differentiation and melanogenesis. KIT mutations usually cause varied changes in coat colour in mammalian species. In this study, we used a pair of single-guide RNAs (sgRNAs) to delete exon 17 of KIT in somatic cells isolated from two different Chinese Li Hua feline foetuses. Edited cells were used as donor nuclei for somatic cell nuclear transfer (SCNT) to generate cloned embryos presenting an average cleavage rate exceeding 85%, and an average blastocyst formation rate exceeding 9.5%. 131 cloned embryos were transplanted into four surrogates, and all surrogates carried their pregnancies to term, and delivered 4.58% (6/131) alive cloned kittens, with 1.53% (2/131) being KIT-edited heterozygotes (KITD17/+). The KITD17/+ cats presented an obvious darkness reduction in the mackerel tabby coat. Immunohistochemical analysis (IHC) of skin tissues indicated impaired proliferation and differentiation of melanoblasts caused by the lack of exon17 in feline KIT. To our knowledge, this is the first report on coat colour modification of cats through gene editing. The findings could facilitate further understanding of the regulatory role of KIT on feline coat colour and provide a basis for the breeding of cats with commercially desired coat colour.

Preparation of Mesophase Pitch with Fine-Flow Texture from Ethylene Tar/Naphthalene by Catalytic Synthesis for High-Thermal-Conductivity Carbon Fibers.

Mesophase pitch is usually prepared by radical polymerization or catalytic polymerization from coal tar, petroleum, and aromatic compounds, and the catalytic synthesis of mesophase pitch from pure aromatic compounds is more controllable in the preparation of high-quality mesophase pitch. However, the corrosive and highly toxic nature of the catalyst has limited the further development of this method. In this study, mesophase pitch was synthetized using ethylene tar and naphthalene as raw materials and boron trifluoride diethyl etherate as a catalyst. The effect of the catalytic reaction on the structure and properties of the mesophase pitch was investigated. The results show that naphthalene plays an important role in the mesophase content and reaction pressure (from above 6 MPa to 2.35 MPa). Mesophase pitch with fine-flow texture can be prepared by introducing more methylene groups, naphthenic structures, and aliphatic hydrocarbons during synthesis. Carbon fibers prepared from mesophase pitch show a split structure, and the thermal conductivity is 730 W/(m·K). This work provides theoretical support for lower toxicity and causticity and for reaction-controlled technology for the synthesis of high-purity mesophase pitch.

[Retracted] Intracisternal administration of an interleukin­6 receptor antagonist attenuates surgery­induced cognitive impairment by inhibition of neuroinflammatory responses in aged rats.

[This retracts the article DOI: 10.3892/etm.2014.2149.].

Dexamethasone Suppresses IL-33-exacerbated Malignant Phenotype of U87MG Glioblastoma Cells via NF-κB and MAPK Signaling Pathways.

BACKGROUND: Interleukin (IL)-33 is highly expressed in glioblastoma (GBM) and promotes tumor progression. Targeting IL-33 may be an effective strategy for the treatment of GBM. Dexamethasone (DEX) is a controversial drug routinely used clinically in GBM therapy. Whether DEX has an effect on IL-33 is unknown. This study aimed to investigate the effect of DEX on IL-33 and the molecular mechanisms involved. METHODS: U87MG cells were induced by tumor necrosis factor (TNF)-α to express IL-33 and then treated with DEX. The mRNA levels of IL-33, NF-κB p65, ERK1/2, and p38 were determined by real-time quantitative PCR. The expression of IL-33, IkBα (a specific inhibitor of NF-κB) and MKP-1 (a negative regulator of MAPK), as well as the phosphorylation of NF-κB, ERK1/2 and p38 MAPK, were detected by Western blotting. The secretion of IL-33 was measured by ELISA. The proliferation, migration and invasion of U87MG cells were detected by CCK8 and transwell assays, respectively. RESULTS: DEX significantly reduced TNF-α-induced production of IL-33 in U87MG cells, which was dependent on inhibiting the activation of the NF-κB, ERK1/2 and p38 MAPK signaling pathways, and was accompanied by the increased expression of IkBα but not MKP-1. Furthermore, the proliferation, migration and invasion of U87MG cells exacerbated by IL-33 were suppressed by DEX. CONCLUSION: DEX inhibited the production and tumor-promoting function of IL-33. Whether DEX can benefit GBM patients remains controversial. Our results suggest that GBM patients with high IL-33 expression may benefit from DEX treatment and deserve further investigation.

Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS).

Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).

Association between miR-365 polymorphism and ischemic stroke in a Chinese population.

Background: Ischemic stroke (IS) represents a major cause of morbidity and mortality across the globe. The aberrant expression of miR-365 has been found to be implicated in a wide array of human diseases, including atherosclerosis and cancer. Studies on single-nucleotide polymorphisms (SNPs) in miRNA genes can help gain insight into the susceptibility to the condition. This study aimed to examine the relationship between miR-365 SNPs and the risk of IS. Methods: The study recruited 215 IS patients and 220 controls. The SNPscans genotyping was employed to genotype three polymorphic loci (rs121224, rs30230, and rs178553) of miR-365. The relative expression of miR-365 in peripheral blood mononuclear cells of the patients and controls was determined by using real-time quantitative PCR. Results: The miR-365 rs30230 polymorphism exhibited a significant association with the risk of developing IS (TC vs. CC: adjusted OR = 0.55, 95% CI: 0.33-0.92, P = 0.022; TT vs. CC: adjusted OR = 0.34, 95% CI: 0.14-0.85, P = 0.021; TC +TT vs. CC: adjusted OR = 0.51, 95% CI: 0.31-0.83, P = 0.007; T vs. C: adjusted OR = 0.57, 95% CI: 0.39-0.83, P = 0.004). Haplotype analysis revealed that the C-T-G haplotype was associated with a decreased risk of IS (OR = 0.68, 95% CI: 0.46-1.00, P = 0.047). Furthermore, miR-365 expression was significantly higher in IS patients than in controls (P < 0.001). Interestingly, patients with rs30230 TC or TT genotypes had lower miR-365 levels compared to their counterparts with CC genotypes (P < 0.001). Conclusions: The miR-365 rs30230 polymorphism might bear an association with IS susceptibility in the Chinese population, and the rs30230 TC/TT genotype might be a protective factor against IS.

An enterovirus A71 virus-like particle with replaced loops confers partial cross-protection in mice.

Enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and CV-A10 belong to the main prevailing types causing hand-foot-and-mouth disease. Since EV-A71 monovalent vaccine does not confer cross-protection, developing a multivalent vaccine is essential. In this study, a trivalent chimeric virus-like particle of EV-A71 (EV-A71-VLPCHI3) was constructed based on EV-A71-VLP backbone by replacing the corresponding surface loops with CV-A16 VP1 G-H, CV-A10 VP1 B-C and E-F loops, which are critical for immunogenic neutralization. The baculovirus-insect cell expression system was employed for EV-A71-VLPCHI3 production. EV-A71-VLPCHI3 was purified by sucrose density gradient and observed by transmission electron microscopy. The immunogenicity and protective efficacy of EV-A71-VLPCHI3 were evaluated in mice. Our results revealed that EV-A71-VLPCHI3 had a similar morphology to inactivated EV-A71 particles and could induce specific IgG antibodies against EV-A71, CV-A16 and CV-A10 in mice. More importantly, EV-A71-VLPCHI3 enhanced cross-reactive protection against CV-A16 and CV-A10, by 20 % and 40 %, compared to inactivated EV-A71 counterparts, respectively. In conclusion, the successful construction of EV-A71-VLPCHI3 suggested that loop-dependent heterologous protection could be transferred by loops replacement on the surface of viral capsid. This strategy may also supplement the development of multivalent vaccines against other infectious viral diseases.

Laparoscopy-assisted gastrectomy for advanced gastric cancer patients with situs inversus totalis: Two case reports and review of literature.

BACKGROUND: Situs inversus totalis (SIT) is a rare condition in which the positions of abdominal and thoracic organs present a "mirror image" of the normal ones in the median sagittal plane. Although minimally invasive surgery has evolved to achieve laparoscopic gastrectomy for gastric cancer (GC) patients with SIT, it is difficult to perform lymphadenectomy (LND) in such a transposed anatomical condition. Herein, we report the cases of two patients with SIT who successfully underwent laparoscopy-assisted gastrectomy (LAG) with D2 LND. CASE SUMMARY: Case 1: A 65-year-old man was admitted for intermittent abdominal pain and distension, occasional belching, and acid reflux for 4 mo. He was diagnosed with GC (cT3N1-2M0) with SIT. Before surgery, he had undergone four cycles of neoadjuvant chemotherapy and immunotherapy. Then, the patient was evaluated as having a partial response, and laparoscopy-assisted distal gastrectomy with D2 LND and Billroth II reconstruction were performed. The operation was performed successfully within 240 min with an estimated blood loss of 50 mL and no severe complications. The patient was discharged on postoperative day (POD) 9. Case 2: A 55-year-old man was admitted for upper abdominal distension with pain and discomfort after eating for 3 mo. He was diagnosed with GC (cT3N1M0) with SIT. He had a history of hypertension for more than 10 years; however, his blood pressure was well-controlled via regular medication. We performed laparoscopy-assisted total gastrectomy with D2 LND and Roux-en-Y reconstruction. The operation was performed successfully within 168 min with an estimated blood loss of 50 mL and no severe complications. The patient was discharged on POD 10. CONCLUSION: LAG with D2 LND could be considered an accessible, safe, and curative procedure for advanced GC patients with SIT.

Left epigastric isolated tumor fed by the inferior phrenic artery diagnosed as ectopic hepatocellular carcinoma: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging. CASE SUMMARY: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen. The patient had no history of hepatitis, did not drink alcohol, and had no family history of cancer. Abdominal contrast-enhanced computed tomography (CT) revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm, with blood supplied by the left inferior phrenic artery. The patient underwent laparoscopic surgery, and HCC was identified by postoperative pathology. Additionally, specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC. The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery. Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis. CONCLUSION: This asymptomatic ectopic HCC case described achieved an excellent result due to early detection, radical resection, and systematic surveillance.

Largely Enhanced Surface Flashover Voltage of Poly(ether Imide) by Scalable and Durable ZnO Coating: A Gift from In Situ Growth.

Dielectric materials with high surface electric insulation strength are in great demand in a high-power space solar cell array (SSCA). A moderately conductive surface is favorable to inhibit charge accumulation and mitigate electric field distortion, thus improving the surface flashover voltage. Although numerous modification methods have been proposed to achieve this goal, the facile, efficient, scalable, and environmentally friendly modification strategy remains a critical challenge to date. Considering the excellent charge modulation ability of ZnO and its mild preparation conditions, a facile and economical hydrothermal strategy was proposed to fabricate in situ a durable poly(ether imide)/zinc oxide (PEI/ZnO) coating with a high charge decay rate. The blooming flower-like ZnO in the coating is proved to play a key role in enhancing lateral charge dissipation on the surface of PEI, thereby suppressing surface charge accumulation. It was also shown that the shielding effect of ZnO on high-energy photons during flashover and the catalytic effect of Zn2+ on PEI molecular chains during hydrothermal treatment had a facilitating and suppressing effect on outgassing, respectively, and consequently affected the flashover. Excitingly, the synergistic effects of both accelerated charge dissipation and suppressed outgassing helped to improve the flashover voltage of PEI by up to 36.7%. The strategy selected here is efficient, scalable, and facile, and the coating is durable, which makes sense for commercial promotion.

Unified Mouse and Human Kidney Single-Cell Expression Atlas Reveal Commonalities and Differences in Disease States.

SIGNIFICANCE STATEMENT: Mouse models have been widely used to understand kidney disease pathomechanisms and play an important role in drug discovery. However, these models have not been systematically analyzed and compared. The authors characterized 18 different mouse kidney disease models at both bulk and single-cell gene expression levels and compared single-cell gene expression data from diabetic kidney disease (DKD) mice and from patients with DKD. Although single cell-level gene expression changes were mostly model-specific, different disease models showed similar changes when compared at a pathway level. The authors also found that changes in fractions of cell types are major drivers of bulk gene expression differences. Although the authors found only a small overlap of single cell-level gene expression changes between the mouse DKD model and patients, they observed consistent pathway-level changes. BACKGROUND: Mouse models have been widely used to understand kidney disease pathomechanisms and play an important role in drug discovery. However, these models have not been systematically analyzed and compared. METHODS: We analyzed single-cell RNA sequencing data (36 samples) and bulk gene expression data (42 samples) from 18 commonly used mouse kidney disease models. We compared single-nucleus RNA sequencing data from a mouse diabetic kidney disease model with data from patients with diabetic kidney disease and healthy controls. RESULTS: We generated a uniformly processed mouse single-cell atlas containing information for nearly 300,000 cells, identifying all major kidney cell types and states. Our analysis revealed that changes in fractions of cell types are major drivers of differences in bulk gene expression. Although gene expression changes at the single-cell level were mostly model-specific, different disease models showed similar changes when compared at a pathway level. Tensor decomposition analysis highlighted the important changes in proximal tubule cells in disease states. Specifically, we identified important alterations in expression of metabolic and inflammation-associated pathways. The mouse diabetic kidney disease model and patients with diabetic kidney disease shared only a small number of conserved cell type-specific differentially expressed genes, but we observed pathway-level activation patterns conserved between mouse and human diabetic kidney disease samples. CONCLUSIONS: This study provides a comprehensive mouse kidney single-cell atlas and defines gene expression commonalities and differences in disease states in mice. The results highlight the key role of cell heterogeneity in driving changes in bulk gene expression and the limited overlap of single-cell gene expression changes between animal models and patients, but they also reveal consistent pathway-level changes.

Deletion of protein tyrosine phosphatase SHP-1 restores SUMOylation of podocin and reverses the progression of diabetic kidney disease.

Both clinical and experimental data suggest that podocyte injury is involved in the onset and progression of diabetic kidney disease (DKD). Although the mechanisms underlying the development of podocyte loss are not completely understood, critical structural proteins such as podocin play a major role in podocyte survival and function. We have reported that the protein tyrosine phosphatase SHP-1 expression increased in podocytes of diabetic mice and glomeruli of patients with diabetes. However, the in vivo contribution of SHP-1 in podocytes is unknown. Conditional podocyte-specific SHP-1-deficient mice (Podo-SHP-1-/-) were generated to evaluate the impact of SHP-1 deletion at four weeks of age (early) prior to the onset of diabetes and after 20 weeks (late) of diabetes (DM; Ins2+/C96Y) on kidney function (albuminuria and glomerular filtration rate) and kidney pathology. Ablation of the SHP-1 gene specifically in podocytes prevented and even reversed the elevated albumin/creatinine ratio, glomerular filtration rate progression, mesangial cell expansion, glomerular hypertrophy, glomerular basement membrane thickening and podocyte foot process effacement induced by diabetes. Moreover, podocyte-specific deletion of SHP-1 at an early and late stage prevented diabetes-induced expression of collagen IV, fibronectin, transforming growth factor-ß, transforming protein RhoA, and serine/threonine kinase ROCK1, whereas it restored nephrin, podocin and cation channel TRPC6 expression. Mass spectrometry analysis revealed that SHP-1 reduced SUMO2 post-translational modification of podocin while podocyte-specific deletion of SHP-1 preserved slit diaphragm protein complexes in the diabetic context. Thus, our data uncovered a new role of SHP-1 in the regulation of cytoskeleton dynamics and slit diaphragm protein expression/stability, and its inhibition preserved podocyte function preventing DKD progression.

Parameterized Gompertz-Guided Morphological AutoEncoder for Predicting Pulmonary Nodule Growth.

The growth rate of pulmonary nodules is a critical clue to the cancerous diagnosis. It is essential to monitor their dynamic progressions during pulmonary nodule management. To facilitate the prosperity of research on nodule growth prediction, we organized and published a temporal dataset called NLSTt with consecutive computed tomography (CT) scans. Based on the self-built dataset, we develop a visual learner to predict the growth for the following CT scan qualitatively and further propose a model to predict the growth rate of pulmonary nodules quantitatively, so that better diagnosis can be achieved with the help of our predicted results. To this end, in this work, we propose a parameterized Gempertz-guided morphological autoencoder (GM-AE) to generate any future-time-span high-quality visual appearances of pulmonary nodules from the baseline CT scan. Specifically, we parameterize a popular mathematical model for tumor growth kinetics, Gompertz, to predict future masses and volumes of pulmonary nodules. Then, we exploit the expected growth rate on the mass and volume to guide decoders generating future shape and texture of pulmonary nodules. We introduce two branches in an autoencoder to encourage shape-aware and textural-aware representation learning and integrate the generated shape into the textural-aware branch to simulate the future morphology of pulmonary nodules. We conduct extensive experiments on the self-built NLSTt dataset to demonstrate the superiority of our GM-AE to its competitive counterparts. Experiment results also reveal the learnable Gompertz function enjoys promising descriptive power in accounting for inter-subject variability of the growth rate for pulmonary nodules. Besides, we evaluate our GM-AE model on an in-house dataset to validate its generalizability and practicality. We make its code publicly available along with the published NLSTt dataset.

Glucose Induces Resistance to Polymyxins in High-Alcohol-Producing Klebsiella pneumoniae via Increasing Capsular Polysaccharide and Maintaining Intracellular ATP.

High-alcohol-producing K. pneumoniae (HiAlc Kpn) causes nonalcoholic fatty liver disease (NAFLD) by producing excess endogenous alcohol in the gut of patients with NAFLD, using glucose as the main carbon source. The role of glucose in the response of HiAlc Kpn to environmental stresses such as antibiotics remains unclear. In this study, we found that glucose could enhance the resistance of HiAlc Kpn to polymyxins. First, glucose inhibited the expression of crp in HiAlc Kpn and promoted the increase of capsular polysaccharide (CPS), which promoted the drug resistance of HiAlc Kpn. Second, glucose maintained high ATP levels in HiAlc Kpn cells under the pressure of polymyxins, enhancing the resistance of the cells to the killing effect of antibiotics. Notably, the inhibition of CPS formation and the decrease of intracellular ATP levels could both effectively reverse glucose-induced polymyxins resistance. Our work demonstrated the mechanism by which glucose induces polymyxins resistance in HiAlc Kpn, thereby laying the foundation for developing effective treatments for NAFLD caused by HiAlc Kpn. IMPORTANCE HiAlc Kpn can use glucose to produce excess endogenous alcohol for promoting the development of NAFLD. Polymyxins are the last line of antibiotics and are commonly used to treat infections caused by carbapenem-resistant K. pneumoniae. In this study, we found that glucose increased bacterial resistance to polymyxins via increasing CPS and maintaining intracellular ATP; this increases the risk of failure to treat NAFLD caused by multidrug-resistant HiAlc Kpn infection. Further research revealed the important roles of glucose and the global regulator, CRP, in bacterial resistance and found that inhibiting CPS formation and decreasing intracellular ATP levels could effectively reverse glucose-induced polymyxins resistance. Our work reveals that glucose and the regulatory factor CRP can affect the resistance of bacteria to polymyxins, laying a foundation for the treatment of infections caused by multidrug-resistant bacteria.

Transcriptome- and proteome-wide association studies nominate determinants of kidney function and damage.

BACKGROUND: The pathophysiological causes of kidney disease are not fully understood. Here we show that the integration of genome-wide genetic, transcriptomic, and proteomic association studies can nominate causal determinants of kidney function and damage. RESULTS: Through transcriptome-wide association studies (TWAS) in kidney cortex, kidney tubule, liver, and whole blood and proteome-wide association studies (PWAS) in plasma, we assess for effects of 12,893 genes and 1342 proteins on kidney filtration (glomerular filtration rate (GFR) estimated by creatinine; GFR estimated by cystatin C; and blood urea nitrogen) and kidney damage (albuminuria). We find 1561 associations distributed among 260 genomic regions that are supported as putatively causal. We then prioritize 153 of these genomic regions using additional colocalization analyses. Our genome-wide findings are supported by existing knowledge (animal models for MANBA, DACH1, SH3YL1, INHBB), exceed the underlying GWAS signals (28 region-trait combinations without significant GWAS hit), identify independent gene/protein-trait associations within the same genomic region (INHBC, SPRYD4), nominate tissues underlying the associations (tubule expression of NRBP1), and distinguish markers of kidney filtration from those with a role in creatinine and cystatin C metabolism. Furthermore, we follow up on members of the TGF-beta superfamily of proteins and find a prognostic value of INHBC for kidney disease progression even after adjustment for measured glomerular filtration rate (GFR). CONCLUSION: In summary, this study combines multimodal, genome-wide association studies to generate a catalog of putatively causal target genes and proteins relevant to kidney function and damage which can guide follow-up studies in physiology, basic science, and clinical medicine.

The relationship between single nucleotide polymorphisms and skin cancer susceptibility: A systematic review and network meta-analysis.

Background: Single nucleotide polymorphisms (SNPs) interfere with the function of certain genes and thus may influence the probability of skin cancer. The correlation between SNPs and skin cancer (SC) lacks statistical power, however. Therefore, the purpose of this study was to identify the gene polymorphisms involved in skin cancer susceptibility using network meta-analysis and to determine the relationship between SNPs and SC risk. Methods: PubMed, Embase, and Web of Science were searched for articles including "SNP" and different types of SC as keywords between January 2005 and May 2022. The Newcastle-Ottawa Scale was used to assess bias judgments. The odds ratio (ORs) and their 95% confidence intervals (CIs) were determined to estimate heterogeneity within and between studies. Meta-analysis and network meta-analysis were carried out to identify the SNPs associated with SC. The P-score of each SNP was compared to obtain the rank of probability. Subgroup analyses were performed by cancer type. Results: A total of 275 SNPs from 59 studies were included in the study. Two subgroup SNP networks using the allele model and dominant model were analyzed. The alternative alleles of rs2228570 (FokI) and rs13181 (ERCC2) were the first-ranking SNPs in both subgroups one and two of the allele model, respectively. The homozygous dominant genotype and heterozygous genotype of rs475007 in subgroup one and the homozygous recessive genotype of rs238406 in subgroup two were most likely to be associated with skin cancer based on the dominant model. Conclusions: According to the allele model, SNPs FokI rs2228570 and ERCC2 rs13181 and, according to the dominant model, SNPs MMP1 rs475007 and ERCC2 rs238406 are closely linked to SC risk.

Circ_0002715 promotes the development of osteoarthritis through regulating LXN by sponging miR-127-5p.

BACKGROUND: Our study aims to investigate the role and mechanism of circular RNA_0002715 (circ_0002715) in osteoarthritis (OA) progression. METHODS: IL-1ß-induced CHON-001 cells were used to mimic OA cell model. Circ_0002715, microRNA (miR)-127-5p and Latexin (LXN) expression was detected by quantitative real-time PCR. Cell functions were determined by MTT assay, flow cytometry and ELISA assay. Protein expression was examined by western blot. RESULTS: Circ_0002715 was highly expressed in OA cartilage tissues. Circ_0002715 silencing inhibited inflammation, apoptosis, and ECM degradation in IL-1ß-interfered CHON-001 cells. Circ_0002715 could sponge miR-127-5p, and miR-127-5p could target LXN. The effect of circ_0002715 down-regulation on chondrocyte injury was partially restored by miR-127-5p inhibitor. MiR-127-5p could suppress chondrocyte injury by inhibiting LXN expression. CONCLUSION: Circ_0002715 might be a new therapeutic target for OA, which regulated miR-127-5p/LXN axis to promote IL-1ß-induced chondrocyte injury.

Single internal carotid cavernous sinus aneurysm presented as bilateral painful ophthalmoplegia: a case report.

BACKGROUND: Intracranial aneurysms are the most common vascular cause of painful ophthalmoplegia. Symptoms include retro-orbital pain, diplopia, ophthalmoplegia, trigeminal neuropathy, or a combination of these. Most single aneurysms cause ipsilateral, painful ophthalmoplegia. Here, we report the first, to our knowledge, case of bilateral painful ophthalmoplegia possibly caused by an aneurysm of the cavernous segment of the left internal carotid artery. CASE PRESENTATION: A 62-year-old male patient presented with headache and bilateral ptosis. Laboratory tests revealed hypopituitary function. Computerized tomography angiography showed a large aneurysm in the cavernous sinus segment of the left internal carotid artery. Aneurysm embolization was performed in the Nerve Interventional Department. Four months after surgery, the patient's symptoms returned to normal. CONCLUSIONS: This case suggests that patients with bilateral painful ophthalmoplegia should be screened for aneurysms using computed tomography angiography or magnetic resonance angiography immediately.