Detection and population genetic analysis of Aedes albopictus (Diptera: Culicidae) based on knockdown resistance (kdr) mutations in the Yangtze River basin of China.

BACKGROUND: Aedes albopictus is an important vector of chikungunya, dengue, yellow fever and Zika viruses. Insecticides are often the most effective tools for rapidly decreasing the density of vector populations, especially during arbovirus disease outbreaks. However, the intense use of insecticides, particularly pyrethroids, has led to the selection of resistant mosquito populations worldwide. Mutations in the voltage-gated sodium channel (VGSC) gene are one of the main drivers of insecticide resistance in Ae. albopictus and are also known as "knockdown resistance" (kdr) mutations. Knowledge about genetic mutations associated with insecticide resistance is a prerequisite for developing techniques for rapid resistance diagnosis. Here, we report studies on the origin and dispersion of kdr haplotypes in samples of Ae. albopictus from the Yangtze River Basin, China; METHODS: Here, we report the results of PCR genotyping of kdr mutations in 541 Ae. albopictus specimens from 22 sampling sites in 7 provinces and municipalities in the Yangtze River Basin. Partial DNA sequences of domain II and domain III of the VGSC gene were amplified. These DNA fragments were subsequently sequenced to discover the possible genetic mutations mediating knockdown resistance (kdr) to pyrethroids. The frequency and distribution of kdr mutations were assessed in 22 Ae. albopictus populations. Phylogenetic relationships among the haplotypes were used to infer whether the kdr mutations had a single or multiple origins; RESULTS: The kdr mutation at the 1016 locus had 2 alleles with 3 genotypes: V/V (73.38%), V/G (26.43%) and G/G (0.18%). The 1016G homozygous mutation was found in only one case in the CQSL strain in Chongqing, and no 1016G mutations were detected in the SHJD (Shanghai), NJDX (Jiangsu) or HBQN (Hubei) strains. A total of 1532 locus had two alleles and three genotypes, I/I (88.35%), I/T (8.50%) and T/T (3.14%). A total of 1534 locus had four alleles and six genotypes: F/F (49.35%), F/S (19.96%), F/C (1.48%) and F/L (0.18%); S/S (23.66%); and C/C (5.36%). Haplotypes with the F1534C mutation were found only in Ae. albopictus populations in Chongqing and Hubei, and C1534C was found only in three geographic strains in Chongqing. Haplotypes with the 1534S mutation were found only in Ae. albopictus populations in Sichuan and Shanghai. F1534L was found only in HBYC. The Ae. albopictus populations in Shanghai were more genetically differentiated from those in the other regions (except Sichuan), and the genetic differentiation between the populations in Chongqing and those in the middle-lower reaches of the Yangtze River (Huber, Jiangsu, Jiangxi, and Anhui) was lower. Shanghai and Sichuan displayed low haplotype diversity and low nucleotide diversity. Phylogenetic analysis and sequence comparison revealed that the 1016 locus was divided into three branches, with the Clade A and Clade B branches bearing the 1016 mutation occurring mostly in Jiangsu and the Clade C branch bearing the 1016 mutation occurring mostly in Chongqing, suggesting at least two origins for 1016G. IIIS6 phylogenetic analysis and sequence comparison revealed that F1534S, F1534C and I1532T can be divided into two branches, indicating that IIIS6 has two origins; CONCLUSIONS: Combined with the distribution of kdr mutations and the analysis of population genetics, we infer that besides the local selection of pyrethroid resistance mutations, dispersal and colonization of Ae. albopictus from other regions may explain why kdr mutations are present in some Ae. albopictus populations in the Yangtze River Basin.

Effect of Specific Spoilage Organisms on the Degradation of ATP-Related Compounds in Vacuum-Packed Refrigerated Large Yellow Croaker (Larimichthys crocea).

This study examined the spoilage potential of specific spoilage organisms on the degradation of adenosine triphosphate (ATP)-related compounds in vacuum-packed refrigerated large yellow croaker. The total viable count (TVC), ATP-related compounds and related enzymes of vacuum-packed refrigerated large yellow croaker inoculated with different bacteria (Pseudomonas fluorescens and Shewanella putrefaciens) were characterized using the spread plate method, high-performance liquid chromatography and assay kits, respectively. Results indicated that the TVC for both control and Shewanella putrefaciens groups reached spoilage levels at days 9 and 15, respectively. The changes of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine deaminase activity across all groups showed no significant difference attributable to microbial growth. The results suggested that ATP to inosine monophosphate (IMP) degradation primarily occurs via fish's endogenous enzymes, with minimal microbial involvement. On day 12, the IMP content in fillets inoculated with Pseudomonas fluorescens (0.93 µmol/g) was half higher than in those inoculated with Shewanella putrefaciens (0.57 µmol/g). Both spoilage organisms facilitated IMP degradation, with Shewanella putrefaciens making a more substantial contribution. Analysis of K values and correlation coefficients revealed that Shewanella putrefaciens was the primary factor in the freshness loss of refrigerated vacuum-packed large yellow croaker. These findings offer a reference for understanding quality changes in refrigerated large yellow croaker, especially regarding umami degradation at the microbial level.

Effect of different freezing conditions on ice crystal formation behavior and ice-growth inhibition by cryoprotectants.

BACKGROUND: The formation of ice crystals will have adverse effects on aquatic products, and the key to ensure the long-term preservation and better quality preservations of the product is to evaluate the intercellular ice crystal formation to find suitable refrigeration conditions and cryoprotectants. RESULTS: The ice crystal formation was successfully captured by using an inverted microscope cryomicroscopic system equipped with a low-temperature stage, the ice crystals formed under different freezing methods between tuna muscle cells were observed directly, the deformation degree of muscle tissue pores during crystallization was evaluated, and the effect of freeze-thaw times on tuna samples was analyzed. The effects of the use of cryoprotectant such as cellobiose and carboxylated cellulose nanofibers on ice-growth inhibition were investigated, and the reliability of the ice crystal observation results was further verified by the determination of physical properties. The results showed that carboxylated cellulose nanofibers had the best ice-growth inhibition effect, they prevented about 50% cell deformation compared with the control group, and also reduced the minimum size of ice crystal formation. In addition, the addition of cellobiose and sodium tripolyphosphate gave the ice crystals a more uniform size and roundness. CONCLUSION: The experiment proposed a stable and clear observation method for the process of intercellular ice crystal formation, and the accuracy of the observation method was further verified by some physical indicators. This may help in the selection of suitable measurement methods to directly observe ice crystal formation behavior and screen cryoprotectants. © 2024 Society of Chemical Industry.

Distinct Thalamo-Subcortical Circuits Underlie Painful Behavior and Depression-Like Behavior Following Nerve Injury.

Clinically, chronic pain and depression often coexist in multiple diseases and reciprocally reinforce each other, which greatly escalates the difficulty of treatment. The neural circuit mechanism underlying the chronic pain/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVPGlu) send signals to GABAergic neurons (VLPAGGABA) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVAGlu) send signals to the nucleus accumbens D1-positive neurons and D2-positive neurons (NAcD1→D2), which is involved in depression-like behavior in comorbidity. This study demonstrates that the distinct thalamo-subcortical circuits PVPGlu→VLPAGGABA and PVAGlu→NAcD1→D2 mediated painful behavior and depression-like behavior following spared nerve injury (SNI), respectively, which provides the circuit-based potential targets for preventing and treating comorbidity.

Magnetic-navigable silk fibroin microneedles for oral drug delivery: Ensuring long-lasting helicobacter pylori eradication and rapid hemostasis in the stomach.

The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.

Clinical Trial Protocol for VIOLET: A Single-Center, Phase I/II Trial Evaluation of Radioligand Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer with [161Tb]Tb-PSMA-I&T.

[177Lu]Lu-PSMA is an effective class of therapy for patients with metastatic castration-resistant prostate cancer (mCRPC); however, progression is inevitable. The limited durability of response may be partially explained by the presence of micrometastatic deposits, which are energy-sheltered and receive low absorbed radiation with 177Lu due to the approximately 0.7-mm mean pathlength. 161Tb has abundant emission of Auger and conversion electrons that deposit a higher concentration of radiation over a shorter path, particularly to single tumor cells and micrometastases. 161Tb has shown in vitro and in vivo efficacy superior to that of 177Lu. We aim to demonstrate that [161Tb]Tb-PSMA-I&T will deliver effective radiation to sites of metastatic prostate cancer with an acceptable safety profile. Methods: This single-center, single-arm, phase I/II trial will recruit 30 patients with mCRPC. Key eligibility criteria include a diagnosis of mCRPC with progression after at least one line of taxane chemotherapy (unless medically unsuitable) and androgen receptor pathway inhibitor; prostate-specific membrane antigen-positive disease on [68Ga]Ga-PSMA-11 or [18F]DCFPyL PET/CT (SUVmax ≥ 20); no sites of discordance on [18F]FDG PET/CT; adequate bone marrow, hepatic, and renal function; an Eastern Cooperative Oncology Group performance status of no more than 2, and no prior treatment with another radioisotope. The dose escalation is a 3 + 3 design to establish the safety of 3 prespecified activities of [161Tb]Tb-PSMA-I&T (4.4, 5.5, and 7.4 GBq). The maximum tolerated dose will be defined as the highest activity level at which a dose-limiting toxicity occurs in fewer than 2 of 6 participants. The dose expansion will include 24 participants at the maximum tolerated dose. Up to 6 cycles of [161Tb]Tb-PSMA-I&T will be administered intravenously every 6 wk, with each subsequent activity reduced by 0.4 GBq. The coprimary objectives are to establish the maximum tolerated dose and safety profile (Common Terminology Criteria for Adverse Events version 5.0) of [161Tb]Tb-PSMA-I&T. Secondary objectives include measuring absorbed radiation dose (Gy), evaluating antitumor activity (prostate-specific antigen 50% response rate, radiographic and prostate-specific antigen progression-free survival, overall survival, objective response rate), and evaluating pain (Brief Pain Inventory-Short Form) and health-related quality of life (Functional Assessment of Cancer Therapy-Prostate and Functional Assessment of Cancer Therapy-Radionuclide Therapy). Conclusion: Enrollment was completed in February 2024. Patients are still receiving [161Tb]Tb-PSMA-I&T.

Targeting HTR2B suppresses non-functioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.

BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.

Adaptive Dynamic Event-Triggered Tracking Control for Uncertain Switched Nonlinear Systems Under State-Dependent Switching.

This article introduces an adaptive dynamic event-triggered technique for addressing the output tracking control problem of uncertain switched nonlinear systems with prescribed performance. First, a switching dynamic event-triggered mechanism (SDETM) is established to alleviate network burden and conserve computational resources. A notable aspect is the inclusion of asynchronous switching between the switching subsystems and controllers. Second, a state-dependent switching law ensuring a dwell-time constraint is designed, which avoids the frequent switching phenomenon within any finite time interval. Third, an SDETM and an adaptive dynamic event-triggered controller are developed to confine the output tracking error within predefined decaying boundaries, while ensuring that all the signals of the closed-loop switched system remain within bounded regions. Finally, the validity and applicability of the developed control scheme are demonstrated through a one-link manipulator example.

Integrative analysis of the transcriptome and metabolome provides insights into polysaccharide accumulation in Polygonatum odoratum (Mill.) Druce rhizome.

Background: Polygonatum odoratum (Mill.) Druce is a traditional Chinese herb that is widely cultivated in China. Polysaccharides are the major bioactive components in rhizome of P. odoratum and have many important biological functions. Methods: To better understand the regulatory mechanisms of polysaccharide accumulation in P. odoratum rhizomes, the rhizomes of two P. odoratum cultivars 'Y10' and 'Y11' with distinct differences in polysaccharide content were used for transcriptome and metabolome analyses, and the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were identified. Results: A total of 14,194 differentially expressed genes (DEGs) were identified, of which 6,689 DEGs were down-regulated in 'Y10' compared with those in 'Y11'. KEGG enrichment analysis of the down-regulated DEGs revealed a significant enrichment of 'starch and sucrose metabolism', and 'amino sugar and nucleotide sugar metabolism'. Meanwhile, 80 differentially accumulated metabolites (DAMs) were detected, of which 52 were significantly up-regulated in 'Y11' compared to those in 'Y10'. The up-regulated DAMs were significantly enriched in 'tropane, piperidine and pyridine alkaloid biosynthesis', 'pentose phosphate pathway' and 'ABC transporters'. The integrated metabolomic and transcriptomic analysis have revealed that four DAMs, glucose, beta-D-fructose 6-phosphate, maltose and 3-beta-D-galactosyl-sn-glycerol were significantly enriched for polysaccharide accumulation, which may be regulated by 17 DEGs, including UTP-glucose-1-phosphate uridylyltransferase (UGP2), hexokinase (HK), sucrose synthase (SUS), and UDP-glucose 6-dehydrogenase (UGDH). Furthermore, 8 DEGs (sacA, HK, scrK, GPI) were identified as candidate genes for the accumulation of glucose and beta-D-fructose 6-phosphate in the proposed polysaccharide biosynthetic pathways, and these two metabolites were significantly associated with the expression levels of 13 transcription factors including C3H, FAR1, bHLH and ERF. This study provided comprehensive information on polysaccharide accumulation and laid the foundation for elucidating the molecular mechanisms of medicinal quality formation in P. odoratum rhizomes.

Discovery of mass spectral peak markers and protein biomarkers in fish muscle exudates for rapid and precise recognition of fish species via magnetic beads (MBs) and mass spectrometry.

In this study, muscle exudates from five fishes belonging to the family Sciaenidae, in the order Perciformes, were analyzed as models for the discovery of biomarkers by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). MagSi-weak cation exchange magnetic beads (WCX-MBs) were utilized for the enrichment of proteins from fish exudate samples, allowing protein biomarkers to be identified and subsequently used for fish species differentiation. Buffers with pH ranging from 4.0 to 9.0 can provide an environment for proteins in fish muscle exudate to bind to the WCX-MBs. The optimal enrichment based on WCX-MBs can be achieved when the exudate samples are diluted 100folds. More species-specific biomarkers in mass spectra can be identified when using WCX-MBs. The number of ions that can be considered as peak markers and can differentiate the analyzed fishes increases from 38 to 121 when using WCX-MBs to isolate peptides/protein in fish muscle exudate. Particularly, eight peak markers in mass spectra were assigned to be specific to Nibea albiflora (NA), three peak markers specific to Larimichthys crocea (LC), two peak markers specific to Miichthys miiuy (MM), seven peak markers specific to Collichthys lucidus (CL), and six peak markers specific to Larimichthys polyactis (LP). Furthermore, five proteins were identified based on the characterization of tryptic peptides and their potential to be biomarkers, of which four proteins specific to CL and one specific to LC were identified. The single-blind samples analysis demonstrated that these species-specific peak markers and protein biomarkers can be successfully utilized for corresponding fish recognition. The utilization of WCX-MBs can improve the discovery of fish species-specific biomarkers in fish muscle exudate samples. The present protocol holds potential of being a rapid and accurate identification tool for recognition of fish species.

The Protective Role of Transcript-Induced in Spermiogenesis 40 in Cerebral Ischemia-Reperfusion Injury.

Prompt reperfusion after cerebral ischemia is important to maintain neuronal survival and reduce permanent disability and death. However, the resupply of blood can induce oxidative stress, inflammatory response and apoptosis, further leading to tissue damage. Here, we report the versatile biological roles of transcript-induced in spermiogenesis 40 (Tisp40) in ischemic stroke. We found that the expression of Tisp40 was upregulated in ischemia/reperfusion-induced brain tissues and oxygen glucose deprivation/returned -stimulated neurons. Tisp40 deficiency increased the infarct size and neurological deficit score, and promoted inflammation and apoptosis. Tisp40 overexpression played the opposite role. In vitro, the oxygen glucose deprivation/returned model was established in Tisp40 knockdown and overexpression primary cultured cortical neurons. Tisp40 knockdown can aggravate the process of inflammation and apoptosis, and Tisp40 overexpression ameliorated the aforementioned processes. Mechanistically, Tisp40 protected against ischemic stroke via activating the AKT signaling pathway. Tisp40 may be a new therapeutic target in brain ischemia/reperfusion injury.

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

Global trends in heart failure from 1990 to 2019: An age-period-cohort analysis from the Global Burden of Disease study.

AIMS: This study aimed to analyse the global prevalence and disability trends of heart failure (HF) from 1990 to 2019, considering both sexes and country-specific economic strata. METHODS: This study conducted a secondary analysis employing data from the Global Burden of Disease (GBD) study. The analysis is stratified by sex and Socio-demographic Index (SDI) levels. Through age-period-cohort and Joinpoint regression analyses, we investigated the temporal trends in HF prevalence and years lived with disability (YLDs) during this period. RESULTS: Between 1990 and 2019, the global prevalence of HF surged by 106.3% (95% uncertainty interval: 99.3% to 114.3%), reaching 56.2 million cases in 2019. While all-age prevalence and YLDs increased over the 30 year span, age-standardized rates decreased by 2019. Countries with higher SDI experienced a more pronounced percentage decrease compared with those with lower SDI. Longitudinal analysis revealed an overall improvement in both prevalence and YLDs for HF, albeit with notable disparities between SDI quintiles and sexes. Ischaemic heart disease and hypertensive heart disease emerged as the most rapidly increasing and primarily contributing causes of HF, albeit with variations observed across different countries. The average annual percentage change for prevalence and YLDs over the period was -0.26% and -0.25%, respectively. CONCLUSIONS: This study offers valuable insights into the global burden of HF, considering factors such as population aging, regional disparities, sex differences and aetiological variations. The findings hold significant implications for healthcare planning and resource allocation. Continued assessment of these trends and innovative strategies for HF prevention and management are crucial for addressing this pressing global health concern.

Survey of public knowledge, attitudes, and practices regarding personal protection against COVID-19 in the post-pandemic era.

In the emerging post-pandemic era (the 'wavelet' era), humans must coexist with viruses for the foreseeable future, and personal protective behaviors will largely replace national-level preventive measures. In this new normal, encouraging the public to implement proper personal protective behaviors against the coronavirus disease (COVID-19) is vital to the sustainable development of cities and communities. This knowledge-attitude-practice (KAP) survey conducted in Chengdu (N = 900) narrowed the knowledge gap regarding post-pandemic public practices of protective behavior. Findings show that:(1) approximately 1/3 of the respondents are currently not concerned about COVID-19 at all; (2) respondents with different demographics and individual COVID-19-related factors showed significant differences in practice behaviors indoors and outdoors; (3) vulnerable groups performed better in practice behavior indoors/outdoors; (4) because the public may relax their vigilance outdoors, public places may become a transmission threat in the next outbreak; (5) attitudes are important, but limited incentives for practice; and (6) when knowledge increases beyond a threshold (68.75-75% in this study), protective behaviors decrease. Our results suggest that authorities must continue to educate and motivate the public, extending measures to cover personal protective practices, and have targeted policies for specific demographics to ensure equity in healthcare in the event of another pandemic (COVID-19 and alike crisis). Besides, comparing the results of the current study with similar studies conducted in other parts of the world can provide insights into how different populations respond to and adopt COVID-19 protective behaviors. The epidemiologists can use the data collected by this and other KAP surveys to refine epidemiologic models, which can help predict the spread of the virus and the impact of interventions in different settings.

Vaccine Uptake and Intentions: Insights from a Texas Survey on Factors Influencing COVID-19 Vaccination Decisions.

The effectiveness of COVID-19 vaccines depends on widespread vaccine uptake. Employing a telephone-administered weighted survey with 19,502 participants, we examined the determinants of COVID-19 vaccine acceptance among adults in Texas. We used multiple regression analysis with LASSO-selected variables to identify factors associated with COVID-19 vaccine uptake and intentions to receive the vaccine among the unvaccinated. The prevalence of unvaccinated individuals (22%) was higher among those aged 18-39, males, White respondents, English speakers, uninsured individuals, those facing financial challenges, and individuals expressing no concern about contracting the illness. In a fully adjusted regression model, higher odds of being unvaccinated were observed among males (aOR 1.11), the uninsured (aOR 1.38), smokers (aOR 1.56), and those facing financial struggles (aOR 1.62). Conversely, Asians, Blacks, and Hispanics were less likely to be unvaccinated compared to Whites. Among the unvaccinated, factors associated with stronger intent to receive the vaccine included age (over 65 years), Black and Hispanic ethnicity, and perceived risk of infection. Hispanic individuals, the uninsured, those covered by public insurance, and those facing financial challenges were more likely to encounter barriers to vaccine receipt. These findings underscore the importance of devising tailored strategies, emphasizing nuanced approaches that account for demographic, socioeconomic, and attitudinal factors in vaccine distribution and public health interventions.

TGF-ß2 enhances glycolysis in chondrocytes via TßRI/p-Smad3 signaling pathway.

Chondrocytes rely heavily on glycolysis to maintain the metabolic homeostasis and cartilage matrix turnover. Glycolysis in chondrocytes is remodeled by diverse biochemical and biomechanical factors due to the sporty joint microenvironment. Transforming growth factor-ß2 (TGF-ß2), one of the most abundant TGF-ß superfamily members in chondrocytes, has increasingly attracted attention in cartilage physiology and pathology. Although previous studies have emphasized the importance of TGF-ß superfamily members on cell metabolism, whether and how TGF-ß2 modulates glycolysis in chondrocytes remains elusive. In the current study, we investigated the effects of TGF-ß2 on glycolysis in chondrocytes and explored the underlying biomechanisms. The results showed that TGF-ß2 could enhance glycolysis in chondrocytes by increasing glucose consumption, up-regulating liver-type ATP-dependent 6-phosphofructokinase (Pfkl) expression, and boosting lactate production. The TGF-ß2 signal entered chondrocytes via TGF-ß receptor type I (TßRI), and activated p-Smad3 signaling to regulate the glycolytic pathway. Subsequent experiments employing specific inhibitors of TßRI and p-Smad3 further substantiated the role of TGF-ß2 in enhancement of glycolysis via TßRI/p-Smad3 axis in chondrocytes. The results provide new understanding of the metabolic homeostasis in chondrocytes induced by TGF-ß superfamily and might shed light on the prevention and treatment of related osteoarticular diseases.

Left ventricular remodeling and its correlation with serum cardiac troponin I in patients with end-stage renal disease treated.

OBJECTIVE: To investigate the effects of different blood purification modes on left ventricular remodeling and its relationship with serum cardiac troponin I (cTnI) in patients with end-stage renal disease (ESRD). METHOD: A total of 108 patients with ESRD were selected, 55 cases were divided into hemodialysis combined with hemoperfusion (HD + HP) group, in which patients participants accepted routine hemodialysis for three times/week and hemoperfusion for three times/month; 53 cases in hemodialysis combined with hemodialysis filtration (HD + HDF) group, routine hemodialysis three times/week + hemodialysis filtration three times/month. The total duration of dialysis in the study was 1 year. Cardiac troponin I (cTnI) levels were measured before dialysis and 1 year after treatment, and related parameters were measured by echocardiography, including ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVEDs), and left ventricular myocardial mass index (LVMI). The paired t test was used within the group. Correlation analysis was performed using Spearman correlation analysis. RESULT: After treatment, the levels of cTnI, IVST, LVPWT, LVEDd, LVEDs, and LVMI in the two groups were increased, and the results were statistically significant (all p < 0.05). In addition, cTnI of the two groups was significantly correlated with IVST, LVPWT, LVEDd, LVEDs, and LVMI (all p < 0.05). CONCLUSION: Left ventricular remodeling is common in patients with ESRD, HD + Hp, and HD + HDF cannot reduce the phenomenon of left ventricular remodeling, cTnI can be used as a predictor of left ventricular hypertrophy and enlargement.

Assessing spatiotemporal population density dynamics from 2000 to 2020 in megacities using urban and rural morphologies.

Rapid urbanization has resulted in the substantial population growth in metropolitan areas. However, existing research on population change of the cities predominantly draws on grid statistical data at the administrative level, overlooking the intra-urban variegation of population change. Particularly, there is a lack of attention given to the spatio-temporal change of population across different urban forms and functions. This paper therefore fills in the lacuna by clarifying the spatio-temporal characteristics of population growth in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 2000 to 2020 through the methods of local climate zone (LCZ) scheme and urban-rural gradients. The results showed that: (1) High population density was observed in the compact high-rise (LCZ 1) areas, with a noticeable decline along urban-rural gradients. (2) The city centers of GBA experienced the most significant population growth, while certain urban fringes and rural areas witnessed significant population shrinkage. (3) The rate of growth tended to slow down after 2010, but the uneven development of population-based urbanization was also noticeable, as urbanization and industrialization varied across different LCZ types and cities in GBA. This paper therefore contributes to a deeper understanding of population change and urbanization by clarifying their spatio-temporal contingences at landscape level.

Effects of multi-frequency ultrasound-assisted immersion freezing processing on myofibrillar protein structure and lipid oxidation of large yellow croaker (Larimichthys crocea) during long-time frozen storage.

In this study, large yellow croaker (Larimichthys crocea) was frozen using multi-frequency ultrasound-assisted freezing (MUIF) with different powers (160 W, 175 W, and 190 W, respectively) and stored at -18 °C for ten months. The effect of different ultrasound powers on the myofibrillar protein (MP) structures and lipid oxidation of large yellow croaker was investigated. The results showed that MUIF significantly slowed down the oxidation of MP by inhibiting carbonyl formation and maintaining high sulfhydryl contents. These treatments also held a high activity of Ca2+-ATPase in the MP. MUIF maintained a higher ratio of α-helix to ß-sheet during frozen storage, thereby protecting the secondary structure of the tissue and stabilizing the tertiary structure. In addition, MUIF inhibited the production of thiobarbituric acid reactive substances value and the loss of unsaturated fatty acid content, indicating that MUIF could better inhibit lipid oxidation of large yellow croaker during long-time frozen storage.

The urinary microbiota composition and functionality of calcium oxalate stone formers.

Background: Accumulated evidences indicate that dysbiosis of the urinary microbiota is associated with kidney stone formation. In the present study, we aimed to investigate the urinary microbiota composition and functionality of patients with calcium oxalate stones and compare it with those of healthy individuals. Method: We collected bladder urine samples from 68 adult patients with calcium oxalate stones and 54 age-matched healthy controls by transurethral catheterization. 16S rRNA gene and shotgun sequencing were utilized to characterize the urinary microbiota and functionality associated with calcium oxalate stones. Results: After further exclusion, a total of 100 subjects was finally included and analyzed. The diversity of the urinary microbiota in calcium oxalate stone patients was not significantly different from that of healthy controls. However, the urinary microbiota structure of calcium oxalate stone formers significantly differed from that of healthy controls (PERMANOVA, r = 0.026, P = 0.019). Differential representation of bacteria (e.g., Bifidobacterium) and several enriched functional pathways (e.g., threonine biosynthesis) were identified in the urine of calcium oxalate stone patients. Conclusion: Our results showed significantly different urinary microbiota structure and several enriched functional pathways in calcium oxalate stone patients, which provide new insight into the pathogenesis of calcium oxalate stones.