Lanthanum chloride exerts therapeutic potential for chronic kidney disease by suppressing nanohydroxyapatite-induced mitophagy and mitochondria-mediated apoptosis.

OBJECTIVE: To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism. METHODS: 1. Patients with CKD stage 2-5 were selected to analyze the effect of lanthanum-containing preparations on CKD. 2. Sixty healthy male Wistar rats were randomly divided into control group, model group, lanthanum chloride groups (0.03 ng/kg, 0.1 ng/kg, 0.3 ng/kg, q.3d., i.v.), and lanthanum carbonate group (0.3 g/kg, q.d., p.o.). The model group was given 2 % adenine suspension (200 mg/kg, q.d., p.o.) for the first two weeks, followed by adenine (200 mg/kg, b.i.d., p.o.) for 2 weeks, and all animals were sacrificed after eight weeks of administration. 3. The serum and kidneys of rats in each group were collected to detect the oxidative stress indicators and the expressions of LC3B-Ⅱ/Ⅰ, p62, Bcl-2, Bax, Caspase-3 and Cleaved Caspase-3. 4. Human renal tubular epithelial cells (HK-2 cells) were divided into control group, model group, lanthanum chloride group, pyrophosphate (PPI) group, chloroquine (CQ) group, rapamycin group, doxorubicin (DOX) group and N-acetyl-L-cysteine (NAC) group. The mitochondrial status, mitophagy and apoptosis levels were detected. RESULTS: 1.Lanthanum-containing preparations can significantly reduce the biochemical indexes of kidney injury in patients with CKD. 2. In the model group, the glomerular and renal tubular edema, the mitochondria were short and round, and the expression of LC3B-Ⅱ/Ⅰ and Bax increased, while the expression of P62, Bcl-2 and Caspase-3 decreased, and there was a significant improvement in the administration group, especially the 0.1 ng/kg group and lanthanum carbonate group. 3. In the HK-2 cell model group, mitochondrial membrane potential decreased, morphology changed and the results were reversed by lanthanum chloride. CONCLUSION: Lanthanum chloride may alter the morphology of nano-hydroxyapatite, thereby inhibiting its induced mitophagy and mitochondria-mediated apoptosis, and ultimately improve CKD renal injury effectively.

Pulsed sounds caused by internal oxygen transport during photosynthesis in the seagrass Halophila ovalis.

Oxygen bubbles that leak from seagrass blades during photosynthesis have been hypothesized to cause cavitation sounds in aquatic plants. Here we investigate low-amplitude sounds with regular pulse rates produced during photosynthesis in seagrass beds of Halophila ovalis (Qitou Bay, Penghu islands and Cigu Lagoon, Taiwan). Sound pulses appear in the morning when illumination exceeds 10,000 Lux, peak at midday and decrease in midafternoon on a sunny day. Frequencies peak between 1 to 4 kHz, durations range between ca. 1.8 to 4.8 ms, and sound pressure level 1 cm from the bed is 105.4 ± 0.5 dB re 1 µPa (1100 h on a cloudy day). Sounds attenuate rapidly with distance, disappearing beyond 15 cm. Blocking sunlight or administering herbicide stops ongoing sounds. Gas bubbles are not typically seen during sound production ruling out cavitation, and external force (scissor cutting or plant pressed against the substrate) applied to the patch, leaves, petioles, or rhizomes generally increases pulse rate. We suggest sound emission is caused by internal oxygen transport through pores in diaphragms (a whistle mechanism) at the leaf base and nodes of the rhizome.

Effect of Comprehensive Rehabilitation Training Based on Balance Function on Postoperative Recovery and Function of Hip Fracture in the Elderly: A Systematic Review and Meta-Analysis.

Introduction: In China, the proportion of the elderly population is gradually increasing, followed by the increasing medical demands of elderly patients. Hip fracture is a common fracture in the elderly. The elderly are prone to serious postoperative complications, resulting in failure to restore normal hip function, which seriously affects patients' quality of life and further increases their mortality rate. Thus, hip fracture represents a remarkable public health issue within the realm of geriatric medical care. Significance: This study systematically evaluated the impact of comprehensive rehabilitation training, with a focus on balance function, on elderly individuals with hip fractures' postoperative recovery and functional outcomes. Result: Results showed a significant difference in BBS scores favoring comprehensive rehabilitation training based on balance function over conventional intervention. Similarly, AM-PAC scores favored the balance-focused training. TUTG meta-analysis indicated its adoption in comprehensive rehabilitation training. FIM scores showed improvement with balance-focused training. Harris score meta-analysis also favored this approach. A funnel plot analysis revealed potential publication bias, likely due to study heterogeneity and limited publications. Conclusions: In conclusion, comprehensive rehabilitation training centered around balance function displayed clinical efficacy in enhancing postoperative hip joint function in elderly hip fracture patients. This approach improved balance, coordination, and posture control, facilitating lower limb function recovery and overall prognosis. It holds promise as a valuable treatment approach.

A recoverable hydrophilic deep eutectic solvent for efficient extraction of polyphenolic compounds from raspberry root.

Green deep eutectic solvents (DESs) are widely used to extract bioactive components from plant biomass; however, hydrophilic DES and bioactive component isolation methods have not been developed. In this study, we synthesized hydrophilic DES (CL-CA-DES) using citric acid and choline chloride. We combined this with environmentally friendly anion- and cation-exchange resin column chromatographic isolation methods. This approach extracted and isolated four polyphenolic compounds (catechins, epicatechins, procyanidin B1, and procyanidin B2) from raspberry root and efficiently recovered the hydrophilic DES. CL-CA-DES extracted significantly higher contents of catechin and procyanidin B2 from raspberry root compared to other solvents. It also extracted substantially higher contents of epicatechin compared to butyl alcohol, 70% ethanol, and water, but there was no significant difference when compared with acetone and ethyl acetate. Additionally, CL-CA-DES extracted significantly higher contents of procyanidin B1 compared to butyl alcohol, water, and ethyl acetate, with no significant difference when compared with 70% ethanol and acetone. The isolation efficiency of the bioactive components in the raspberry root extract by anion- and cation-exchange resin column chromatography was higher than that of the organic solvent extraction and precipitation generation methods, and the method was effective in recovering CL-CA-DES with a recovery rate higher than 60%. In conclusion, this study developed a new method for the efficient recovery of hydrophilic CL-CA-DES, which can be used for isolating polyphenolic compounds from raspberry root.

[Dental treatment under general anesthesia among pediatric patients in 120 consecutive cases: a retrospective study].

PURPOSE： To investigate the clinical features of children who received treatment under dental general anesthesia (DGA). METHODS: The clinical records of dental patients below 18 years old who were treated under DGA at the Department of Pediatric Dentistry, Affiliated Dental Hospital of Kunming Medical University during June 2017 to November 2019 were obtained, including the baseline information, causes for DGA, anesthesia methods, intubation methods, treatment items, treatment time and follow-up visits. SPSS 26.0 software package was used to analyze the data. RESULTS: A total of 120 patients were included, 58.3% were males, and children aged 3 to 6 years showed the highest demand for DGA (85.0%). Fear of dental treatment, ineffective non-drug behavior management was the main causes for DGA in young children, while the most common causes for children over 6 years old to choose DGA were mental retardation (38.9%) and patients' needs(38.9%). The average number of teeth treated was (15.16±3.42) for each child, and the average time for treating one tooth was 12.26 min. Restoration, root canal treatment and primary teeth pre-forming crown(including anterior preformed resin transparent crown and posterior preformed metal crown) were the main treatment items. At 1-week follow-up visits, 98.3% of children had no discomfort. During 2017 to 2019, there was an increasing tendency in the number of patients who chose DGA in the authors' institute. CONCLUSIONS： The dental issues of children with fear of dental treatment, ineffectiveor non-drug behavior management or mental retardation can be treated under DGA conveniently, safely and efficiently. The acceptance rate of DGA among pediatric patients is on the rise. DGA training programs and related support projects are needed to meet the treatment demands among patients in less developed areas.

Identification of novel genetic susceptibility loci for calcium-containing kidney stone disease by genome-wide association study and polygenic risk score in a Taiwanese population.

Approximately 80% of kidney stone diseases contain calcium. Inherited genetic factors are among the variables that influence the development of calcium-containing kidney stone diseases (CKSD). Previous genome-wide association studies (GWAS) on stone diseases have been reported worldwide; however, these are not focused on calcium-containing stones. We conducted a GWAS to identify germline genetic polymorphisms associated with CKSD in a Medical Center in Taiwan; hence, this study was based primarily on a hospital-based database. CKSD was diagnosed using the chart records. Patients infected with urea-splitting-microorganisms and those with at least two urinary pH value below 5.5 were excluded. None of the patients had cystic stones based on stone analysis. Those over 40 years of age with no history of CKSD and no microscopic hematuria on urinalysis were considered as controls. The DNA isolated from the blood of 14,934 patients (63.7% male and 36.3% female) with CKSD and 29,868 controls (10,830 men and 19,038 women) at a medical center was genotyped for approximately 714,457 single nucleotide polymorphisms (SNPs) with minor allele frequency of ≥ 0.05. We used PLINK 1.9 to calculate the polygenic risk score (PRS) to investigate the association between CKSD and controls. The accuracy of the PRS was verified by dividing it into the training and testing groups. The statistical analyses were calculated with the area under the curve (AUC) using IBM SPSS version 22. We identified 432 susceptibility loci that reached a genome-wide threshold of P < 1.0 × 10- 5. A total of 132 SNPs reached a threshold of P < 5 × 10- 8 using a stricter definition of significance on chromosomes 4, 13, 16, 17, and 18. At the top locus of our study, SNPs in DGKH, PDILT, BCAS3, and ABCG2 have been previously reported. RN7SKP27, HDAC4, PCDH15, AP003068.2, and NFATC1 were novel findings in this study. PRS was adjusted for sex and age, resulting in an AUC of 0.65. The number of patients in the top quartile of PRS was 1.39 folds in the risk of CKSD than patients in the bottom quartile. Our data identified the significance of GWAS for patients with CKSD in a hospital-based study. The PRS also had a high AUC for discriminating patients with CKSD from controls. A total of 132 SNP loci of SNPs significantly associated with the development of CKSD. This first survey, which focused on patients with CKSD, will provide novel insights specific to CKSD and its potential clinical biomarkers.

miRNAs in patients with alcoholic liver disease: a systematic review and meta-analysis.

INTRODUCTION: Alcoholic liver disease (ALD) encompasses a spectrum of liver conditions, including liver steatosis, alcoholic hepatitis (AH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). microRNAs (miRNAs) have garnered significant interest as potential biomarkers for ALD. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) systemically from inception to June 2024. All extracted data was stratified according to the stages of ALD. The vote-counting strategy performed a meta-analysis on miRNA expression profiles. RESULTS: We included 40 studies. In serum of individuals with alcohol-use vs. no alcohol-use, miRNA-122 and miRNA-155 were upregulated, and miRNA-146a was downregulated. In patients with ALD vs. healthy controls, miRNA-122 and miRNA-155 were also upregulated, and miRNA-146a was downregulated. However, in patients with AH vs. healthy individuals, only the serum miRNA-122 level was upregulated. Due to insufficient data on diagnostic accuracy, we failed to conclude the ability of miRNAs to distinguish between different stages of ALD-related liver fibrosis. The results for ALD-related HCC were also insufficient and controversial. CONCLUSIONS: Circulating miRNA-122 was the most promising biomarker to manage individuals with ALD. More studies were needed for the diagnostic accuracy of miRNAs in ALD. REGISTRATION: This protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (www.crd.york.ac.uk/prospero/) with registration number CRD42023391931.

Hydroxy-Functionalized Ionic Liquids under Pressure: The Influence on Hydrogen Bonding between Ions of Opposite and Like Charges.

Hydroxy functionalization of cations in ionic liquids (ILs) can lead to formation of hydrogen bonds between their OH groups, resulting in so-called (c-c) H-bonds. Thereby, the (c-c) H-bonds compete with regular H-bonds (c-a) between the OH groups and the anions. Polarizable cations, weakly interacting anions, and long alkyl chains at the cation support the propensity for the formation of (c-c) H-bonds. At low temperatures, the equilibrium between (c-c) and (c-a) H-bonds is strongly shifted in favor of the cation-cation interaction. Herein, we clarify the pressure dependence on (c-c) and (c-a) H-bond distributions in the IL 1-(2-hydroxyethyl)-3-methylimidazolium hexafluorophosphate [HOC2C1Im][PF6], in mixtures of [HOC2C1Im][PF6] with the nonhydroxy-functionalized IL 1-propyl-3-methylimidazolium hexafluorophosphate [C3C1Im][PF6] and in [HOC2C1Im][PF6] including trace amounts of water. The infrared (IR) spectra provide clear evidence that the (c-c) H-bonds diminish with increasing pressure in favor of the (c-a) H-bonds. Adding trace amounts of water results in enhanced (c-c) clustering due to cooperative effects. At ambient pressure, the water molecules are involved in the (c-c) H-bond motifs. Increasing pressure leads to squeezing them out of H-bond clusters, finally resulting in demixing of water and the IL at the microscopic level.

Enantioselective and Regiodivergent Synthesis of Propargyl- and Allenylsilanes through Catalytic Propargylic C-H Deprotonation.

We report a highly enantioselective intermolecular C-H bond silylation catalyzed by a phosphoramidite-ligated iridium catalyst. Under reagent-controlled protocols, propargylsilanes resulting from C(sp3)-H functionalization, as well the regioisomeric and synthetically versatile allenylsilanes, could be obtained with excellent levels of enantioselectivity and good to excellent control of propargyl/allenyl selectivity. In the case of unsymmetrical dialkyl acetylenes, good to excellent selectivity for functionalization at the less-hindered site was also observed. A variety of electrophilic silyl sources (R3SiOTf and R3SiNTf2), either commercial or in situ-generated, were used as the silylation reagents, and a broad range of simple and functionalized alkynes, including aryl alkyl acetylenes, dialkyl acetylenes, 1,3-enynes, and drug derivatives were successfully employed as substrates. Detailed mechanistic experiments and DFT calculations suggest that an η3-propargyl/allenyl Ir intermediate is generated upon π-complexation-assisted deprotonation and undergoes outer-sphere attack by the electrophilic silylating reagent to give propargylic silanes, with the latter step identified as the enantiodetermining step.

Sequential Immunizations with Influenza Neuraminidase Protein Followed by Peptide Nanoclusters Induce Heterologous Protection.

Enhancing cross-protections against diverse influenza viruses is desired for influenza vaccinations. Neuraminidase (NA)-specific antibody responses have been found to independently correlate with a broader influenza protection spectrum. Here, we report a sequential immunization regimen that includes priming with NA protein followed by boosting with peptide nanoclusters, with which targeted enhancement of antibody responses in BALB/c mice to certain cross-protective B-cell epitopes of NA was achieved. The nanoclusters were fabricated via desolvation with absolute ethanol and were only composed of composite peptides. Unlike KLH conjugates, peptide nanoclusters would not induce influenza-unrelated immunity. We found that the incorporation of a hemagglutinin peptide of H2-d class II restriction into the composite peptides could be beneficial in enhancing the NA peptide-specific antibody response. Of note, boosters with N2 peptide nanoclusters induced stronger serum cross-reactivities to heterologous N2 and even heterosubtypic N7 and N9 than triple immunizations with the prototype recombinant tetrameric (rt) N2. The mouse challenge experiments with HK68 H3N2 also demonstrated the strong effectiveness of the peptide nanocluster boosters in conferring heterologous protection.

Mendelian-randomization study revealed causal relationship between nonalcoholic fatty liver disease and osteoporosis/fractures.

BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have a higher risk of osteoporosis/fractures; however, the causal relationship remains unclear. METHODS: Publicly available genome-wide association studies (GWASs) were used for Mendelian randomization (MR) analysis. GWASs of NAFLD and fractures were obtained from the FinnGen Consortium. GWASs of bone mineral density (BMD) were derived from a meta-analysis. GWASs of obesity, diabetes, liver function, and serum lipid-related metrics were used to clarify whether the accompanying NAFLD symptoms contributed to fractures. Moreover, two additional GWASs of NAFLD were applied. RESULTS: A causal association was not observed between NAFLD and BMD using GWASs from the FinnGen Consortium. However, a causal relationship between NAFLD and femoral neck-BMD (FN-BMD), a suggestive relationship between fibrosis and FN-BMD, and between NAFLD and osteoporosis were identified in replication GWASs. Genetically proxied body mass index (BMI), high-density lipoprotein (HDL), and hip circumference increased the likelihood of lower limb fractures. The waist-to-hip ratio decreased, whereas glycated hemoglobin (HbA1C) and homeostasis model assessment of ß-cell function (HOMA-B) increased the risk of forearm fractures. Low-density lipoprotein (LDL) reduced, whereas HbA1C increased the incidence of femoral fractures. Alkaline phosphatase (ALP) raised the risk of foot fractures. However, after a multivariate MR analysis (adjusted for BMI), all the relationships became insignificant. CONCLUSIONS: NAFLD caused reduced BMD, and genetically predicted HDL, LDL, HbA1C, HOMA-B, ALP, hip circumference, and waist-to-hip ratio causally increased the risk of fractures. BMI may mediate causal relationships. Larger GWASs are required to verify this finding.

Seven new species and four new records of Psychomyiidae (Insecta, Trichoptera) from China.

Seven new species of the family Psychomyiidae Walker, 1852 are described and illustrated from China; they are Psychomyiashunisp. nov., Ps.mangshanensissp. nov., Ps.capricornissp. nov., Lypesagittalissp. nov., Paduniellafasciariasp. nov., Pa.sanyaensissp. nov., and Tinodesaviformissp. nov. The genus Lype is reported for the first time from mainland China. In addition, four psychomyiids are found to be new to the Chinese caddis fauna: Psychomyiaindra Malicky & Chantaramongkol, 1993; Paduniellaandamanensis Malicky, 1979; Pa.dendrobia Malicky & Chantaramongkol, 1993; and Tinodesgapbona Johanson & Oláh, 2008. Moreover, Psychomyiapolyacantha Li, Qiu & Morse, 2021 is reviewed and synonymized with Psychomyiaimamiah Malicky, 2020.

Self-similar chiral organic molecular cages.

The endeavor to enhance utility of organic molecular cages involves the evolution of them into higher-level chiral superstructures with self-similar, presenting a meaningful yet challenging. In this work, 2D tri-bladed propeller-shaped triphenylbenzene serves as building blocks to synthesize a racemic 3D tri-bladed propeller-shaped helical molecular cage. This cage, in turn, acts as a building block for a pair of higher-level 3D tri-bladed chiral helical molecular cages, featuring multilayer sandwich structures and displaying elegant characteristics with self-similarity in discrete superstructures at different levels. The evolutionary procession of higher-level cages reveals intramolecular self-shielding effects and exclusive chiral narcissistic self-sorting behaviors. Enantiomers higher-level cages can be interconverted by introducing an excess of corresponding chiral cyclohexanediamine. In the solid state, higher-level cages self-assemble into supramolecular architectures of L-helical or D-helical nanofibers, achieving the scale transformation of chiral characteristics from chiral atoms to microscopic and then to mesoscopic levels.

Structural and digestive characters of a heteropolysaccharide fraction from tea (Camellia sinensis L.) flower.

Tea (Camellia sinensis L.) flower polysaccharides (TFPS) have various health-promoting functions. In the present work, the structure of a purified TFPS fraction, namely TFPS-1-3p, and its in vitro digestive properties were investigated. The results demonstrated that TFPS-1-3p was a typical heteropolysaccharide consisting of rhamnose (Rha), arabinose (Ara), galactose (Gal) and galacturonic acid (GalA) with a molecular weight of 47.77 kDa. The backbone of TFPS-1-3p contained â†’ 4)-α-d-GalpA(-6-OMe)-(1 â†’ 4)-α-GalpA-(1 â†’ and â†’ 4)-α-d-GalpA(-6-OMe)-(1 â†’ 2,4)-α-l-Rhap-(1 â†’ linkages. The branch linkages in TFPS-1-3p contained â†’ 6)-ß-d-Galp-(1→, →3,6)-ß-d-Galp-(1→, →5)-α-l-Araf-(1 â†’ and â†’ 3,5)-α-l-Araf-(1 â†’. Subsequently, TFPS-1-3p could not be degraded under simulated human gastrointestinal conditions but could be of use to human fecal microbes, thereby lowering the pH and increasing the production of short-chain fatty acids (SCFAs) of the gut microenvironment and altering the composition of the gut microbiota. The relative abundance of Fusobacterium_mortiferum Megasphaera_elsdenii_DSM_20460, Bacteroides thetaiotaomicron, Bacteroides plebeius and Collinsella aerofaciens increased significantly, potentially contributing to the degradation of TFPS-1-3p.

Sigma-1 receptor activation mediates the sustained antidepressant effect of ketamine in mice via increasing BDNF levels.

Sigma-1 receptor (S1R) is a unique multi-tasking chaperone protein in the endoplasmic reticulum. Since S1R agonists exhibit potent antidepressant-like activity, S1R has become a novel target for antidepression therapy. With a rapid and sustained antidepressant effect, ketamine may also interact with S1R. In this study, we investigated whether the antidepressant action of ketamine was related to S1R activation. Depression state was evaluated in the tail suspension test (TST) and a chronic corticosterone (CORT) procedure was used to induce despair-like behavior in mice. The neuronal activities and structural changes of pyramidal neurons in medial prefrontal cortex (mPFC) were assessed using fiber-optic recording and immunofluorescence staining, respectively. We showed that pharmacological manipulation of S1R modulated ketamine-induced behavioral effect. Furthermore, pretreatment with an S1R antagonist BD1047 (3 mg·kg-1·d-1, i.p., for 3 consecutive days) significantly weakened the structural and functional restoration of pyramidal neuron in mPFC caused by ketamine (10 mg·kg-1, i.p., once). Ketamine indirectly triggered the activation of S1R and subsequently increased the level of BDNF. Pretreatment with an S1R agonist SA4503 (1 mg·kg-1·d-1, i.p., for 3 consecutive days) enhanced the sustained antidepressant effect of ketamine, which was eliminated by knockdown of BDNF in mPFC. These results reveal a critical role of S1R in the sustained antidepressant effect of ketamine, and suggest that a combination of ketamine and S1R agonists may be more beneficial for depression patients.

Circular RNAs in non-alcoholic fatty liver disease: Functions and clinical significance.

Nonalcoholic fatty liver disease (NAFLD), which affects approximately 25% of the global population, is an urgent health issue leading to various metabolic comorbidities. Circular RNAs (circRNAs), covalently closed RNA molecules, are characterized by ubiquity, diversity, stability, and conservatism. Indeed, they participate in various biological processes via distinct mechanisms that could modify the natural history of NAFLD. In this review, we briefly introduce the biogenesis, characteristics, and biological functions of circRNAs. Furthermore, we summarize circRNAs expression profiles in NAFLD by intersecting seven sequencing data sets and describe the cellular roles of circRNAs and their potential advantages as biomarkers of NAFLD. In addition, we emphatically discuss the exosomal non-coding RNA sorting mechanisms and possible functions in recipient cells. Finally, we extensively discuss the potential application of targeting disease-related circRNAs and competing endogenous RNA networks through gain-of-function and loss-of-function approaches in targeted therapy of NAFLD.

2-Bromopalmitate inhibits malignant behaviors of HPSCC cells by hindering the membrane location of Ras protein.

Palmitoylation, which is mediated by protein acyltransferase (PAT) and performs important biological functions, is the only reversible lipid modification in organism. To study the effect of protein palmitoylation on hypopharyngeal squamous cell carcinoma (HPSCC), the expression levels of 23 PATs in tumor tissues of 8 HPSCC patients were determined, and high mRNA and protein levels of DHHC9 and DHHC15 were found. Subsequently, we investigated the effect of 2-bromopalmitate (2BP), a small-molecular inhibitor of protein palmitoylation, on the behavior of Fadu cells in vitro (50 µM) and in nude mouse xenograft models (50 µmol/kg), and found that 2BP suppressed the proliferation, invasion, and migration of Fadu cells without increasing cell apoptosis. Mechanistically, the effect of 2BP on the transduction of BMP, Wnt, Shh, and FGF signaling pathways was tested with qRT-PCR, and its drug target was explored with western blotting and acyl-biotinyl exchange assay. Our results showed that 2BP inhibited the transduction of the FGF/ERK signaling pathway. The palmitoylation level of Ras protein decreased after 2BP treatment, and its distribution in the cell membrane structure was reduced significantly. The findings of this work reveal that protein palmitoylation mediated by DHHC9 and DHHC15 may play important roles in the occurrence and development of HPSCC. 2BP is able to inhibit the malignant biological behaviors of HPSCC cells, possibly via hindering the palmitoylation and membrane location of Ras protein, which might, in turn, offer a low-toxicity anti-cancer drug for targeting the treatment of HPSCC.

Liver cancer stem cell dissemination and metastasis: uncovering the role of NRCAM in hepatocellular carcinoma.

BACKGROUND: Liver cancer stem cells (LCSCs) play an important role in hepatocellular carcinoma (HCC), but the mechanisms that link LCSCs to HCC metastasis remain largely unknown. This study aims to reveal the contributions of NRCAM to LCSC function and HCC metastasis, and further explore its mechanism in detail. METHODS: 117 HCC and 29 non-HCC patients with focal liver lesions were collected and analyzed to assess the association between NRCAM and HCC metastasis. Single-cell RNA sequencing (scRNA-seq) was used to explore the biological characteristics of cells with high NRCAM expression in metastatic HCC. The role and mechanism of NRCAM in LCSC dissemination and metastasis was explored in vitro and in vivo using MYC-driven LCSC organoids from murine liver cells. RESULTS: Serum NRCAM is associated with HCC metastasis and poor prognosis. A scRNA-seq analysis identified that NRCAM was highly expressed in LCSCs with MYC activation in metastatic HCC. Moreover, NRCAM facilitated LCSC migration and invasion, which was confirmed in MYC-driven LCSC organoids. The in vivo tumor allografts demonstrated that NRCAM mediated intra-hepatic/lung HCC metastasis by enhancing the ability of LCSCs to escape from tumors into the bloodstream. Nrcam expression inhibition in LCSCs blocked HCC metastasis. Mechanistically, NRCAM activated epithelial-mesenchymal transition (EMT) and metastasis-related matrix metalloproteinases (MMPs) through the MACF1 mediated ß-catenin signaling pathway in LCSCs. CONCLUSIONS: LCSCs typified by high NRCAM expression have a strong ability to invade and migrate, which is an important factor leading to HCC metastasis.

Soil-transmitted helminthiasis in mainland China from 2016 to 2020: a population-based study.

Background: Soil-transmitted helminthiasis is epidemic in China and many other countries of the world, and has caused substantial burdens to human health. We conducted successive national monitoring in China from 2016 to 2020 to analyze the prevalence, changing trends, and factors influencing soil-transmitted helminthiasis, which provided a reference for future control strategies. Methods: Soil-transmitted helminth monitoring was carried out in 31 provinces (autonomous regions or municipalities, herein after referred to as "provinces") throughout China. Each province determined the number and location of monitoring sites (counties), and a unified sampling method was employed. At least 1,000 subjects were investigated in each monitoring county. Stool samples were collected and the modified Kato-Katz thick smear method was employed for stool examination. Infection data and the details of factors influencing soil-transmitted helminthiasis from 2016 to 2020 were collected from national monitoring sites. Additional influencing factors such as environment, climate and human activities were obtained from authoritative websites. Prevalence of soil-transmitted helminths was presented by species, province, sex, and age group. ArcGIS software was used to conduct spatial autocorrelation and hotspot analysis on the infection data. A Poisson distribution model and SaTScan software were used to analyze the infection data with retrospective spatiotemporal scan statistics. A database was built by matching village-level infection rate data with influencing factors. Subsequently, machine learning methods, including a Linear Regression (LR), a Random Forest (RF), a Gradient Boosted Machine (GBM), and an Extreme gradient boosting (XGBOOST) model was applied to construct a model to analyze the main influencing factors of soil-transmitted helminthiasis. Findings: The infection rates of soil-transmitted helminths at national monitoring sites from 2016 to 2020 were 2.46% (6,456/262,380), 1.78% (5,293/297,078), 1.29% (4,200/326,207), 1.40% (5,959/424,766), and 0.84% (3,485/415,672), respectively. The infection rate of soil-transmitted helminths in 2020 decreased by 65.85% compared to that in 2016. From 2016 to 2020, the infection rate of soil-transmitted helminthiasis was relatively high in southern and southwestern China, including Hainan, Yunnan, Sichuan, Guizhou, and Chongqing. In general, the infection rate was higher in females than in males, with the highest rate in the population aged 60 years and above, and the lowest in children aged 0-6 years. Global autocorrelation and hotspot analyses revealed spatial aggregation in both the national and local distribution of soil-transmitted helminthiasis in China from 2016 to 2020. The hotspots were concentrated in southwestern China. The spatiotemporal scanning analysis revealed aggregation years from 2016 to 2017 located in southwestern China, including Yunnan, Sichuan, Chongqing, Guizhou and Guangxi. The RF model was the best fit model for the infection rate of soil-transmitted helminths in China. The top six influencing factors of this disease in the model were landform, barefoot farming, isothermality, temperature seasonality, year, and the coverage of sanitary toilets. Interpretation: The overall infection rate of soil-transmitted helminths in China showed a decreasing trend from 2016-2020 due to the implementation of control measures and the economic boom in China. However, there are still areas with high infection rates and the distribution of such areas exhibit spatiotemporal aggregation. As a strategic next step, control measures should be adjusted to local conditions based on the main influencing factors and the prevalence of different sites to aid in the control and elimination of soil-transmitted helminthiasis. Funding: This research was funded by the National Key Research and Development Program of China (Grant Nos. 2021YFC2300800 and 2021YFC2300804) and the National Natural Science Foundation of China (Grant No. 32161143036).

Role of extracellular vesicles in nonalcoholic fatty liver disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that affects approximately one-quarter of the global population and is becoming increasingly prevalent worldwide. The lack of current noninvasive tools and efficient treatment is recognized as a significant barrier to the clinical management of these conditions. Extracellular vesicles (EVs) are nanoscale vesicles released by various cells and deliver bioactive molecules to target cells, thereby mediating various processes, including the development of NAFLD. Scope of review: There is still a long way to actualize the application of EVs in NAFLD diagnosis and treatment. Herein, we summarize the roles of EVs in NAFLD and highlight their prospects for clinical application as a novel noninvasive diagnostic tool as well as a promising therapy for NAFLD, owing to their unique physiochemical characteristics. We summarize the literatures on the mechanisms by which EVs act as mediators of intercellular communication by regulating metabolism, insulin resistance, inflammation, immune response, intestinal microecology, and fibrosis in NAFLD. We also discuss future challenges that must be resolved to improve the therapeutic potential of EVs. Major conclusions: The levels and contents of EVs change dynamically at different stages of diseases and this phenomenon may be exploited for establishing sensitive stage-specific markers. EVs also have high application potential as drug delivery systems with low immunogenicity and high biocompatibility and can be easily engineered. Research on the mechanisms and clinical applications of EVs in NAFLD is in its initial phase and the applicability of EVs in NAFLD diagnosis and treatment is expected to grow with technological progress.