Metagenomic unveils the promotion of mainstream PD-anammox process at lower nZVI concentration and inhibition at higher dosage.

The partial-denitrification-anammox (PdNA) process exhibits great potential in enabling the simultaneous removal of NO3--N and NH4+-N. This study delved into the impact of exogenous nano zero-valent iron (nZVI) on the PdNA process. Adding 10 mg L-1 of nZVI increased nitrogen removal efficiency up to 83.12 % and maintained higher relative abundances of certain beneficial bacteria. The maximum relative abundance of Candidatus Brocadia (1.6 %), Candidatus Kuenenia (1.5 %), Ignavibacterium (1.3 %), and Azospira (1.2 %) was observed at 10 mg L-1 of nZVI. However, the greatest relative abundance of Thauera (1.3 %) was recorded under 50 mg L-1. Moreover, applying nZVI selectively enhanced the abundance of NO3--N reductase genes. So, keeping the nZVI concentration at 10 mg L-1 or below is advisable to ensure a stable PdNA process in mainstream conditions. Considering nitrogen removal efficiency, using nZVI in the PD-anammox process could be more cost-effective in enhancing its adoption in industrial and mainstream settings.

Unveiling the multi-dimensional frailty network among older cancer survivors in China: A network analysis study.

INTRODUCTION: Frailty has a significant impact on the overall quality of life of older cancer survivors, but the relationships among frailty symptoms are not well understood. This study aims to explore the specific associations among multidimensional symptoms of frailty among older cancer survivors by employing network analysis to provide supportive evidence for targeted interventions in the future. MATERIALS AND METHODS: Data were obtained by cluster sampling from three large Grade-A tertiary hospitals in Shandong Province, China, and collected through face-to-face interviews by trained investigators. We included patients who were diagnosed with a solid malignant tumor at the age of 60 years or older. Frailty indicators were measured by the Groningen Frailty Indicator (GFI) and analyzed primarily through network analysis, including network estimation, centrality, and stability analysis. The relative importance of a node in a network was tested by centrality analyses, and Spearman correlations were applied to estimate the relationships between symptom pairs (symptom score) and symptom clusters (standardized symptom score) in the symptom network. In terms of centrality, the indexes of strength, closeness, and betweenness were adopted to measure the importance of nodes. RESULTS: Five hundred and eight older cancer survivors were included, with an average age of 68.4 years (standard deviation [SD] = 5.4), and a higher proportion were male (n = 307[60.4%]). The prevalence of frailty among older cancer survivors was 58.9% (n = 299), with a mean GFI score of 4.46 (SD = 2.87). The strongest edge was between "dressing and undressing" and "going to the toilet" (r = 0.58). The nodes with the higher strength centrality were "going to the toilet" (rS=1.09), "walking around outside" (rS=0.97), and "part of social network" (rS=0.96); and the nodes with the higher closeness centrality were "mark physical fitness" (rC=0.005), "calm and relaxed" (rC=0.005), and "nervous or downhearted" (rC=0.005). DISCUSSION: This study demonstrated that older cancer survivors in China have a high prevalence of frailty, with self-care and social participation-related symptoms playing a key role in the multidimensional network of frailty symptoms. Psychological symptoms can rapidly influence other symptoms within this network. Therefore, prioritizing psychological symptoms in the assessment of older adults with cancer is essential for effective frailty management.

Corporate digital transformation and financing constraints: The moderating effect of institutional investors.

In the age of digitization, digital transformation has emerged as a crucial pathway for companies to achieve sustainable development. In a sample of 24,103 firm-year observations from 3,508 listed companies in China's A-share market between 2007 and 2020, we investigate the relationship between corporate digital transformation and financing constraints based on dynamic capability theory. The proportion of intangible assets dedicated to digital technology is employed as a measure of the degree of digital transformation, and the SA index is utilized to assess the level of financing constraints. The findings demonstrate that digital transformation plays a significant role in alleviating financing constraints. In addition, greater institutional ownership leads to a pronounced negative correlation between digital transformation and financing constraints. From the perspective of dynamic capability theory, this study provides empirical evidence supporting research on economic consequences associated with digital transformation. Our results may contribute towards government formulation and implementation of policies promoting digital transformation to create a supportive external environment for businesses. Companies must seize opportunities associated with digital transformation to mitigate financing constraints.

Construction of PCR-SERS Method for Detection of Vibrio parahaemolyticus.

A paper-based surface enhancement of a Raman scattering substrate consisting of silver-nanowires stacked on glass-fiber filter paper was prepared. At the same time, the DNA-embedding molecule Eva Green was introduced as a signaling molecule for surface-enhanced Raman scattering (SERS) detection. Polymerase chain reaction (PCR) was used to amplify target genes and the method was developed into a rapid molecular diagnostic system. The total detection time of the developed detection method was 40 min, including 30 min of PCR amplification and 10 min of SERS measurement. After 30 PCR cycles, bacterial DNA with an initial concentration of 20 fg/µL and a bacterial suspension with an initial concentration of 7.2 × 101 CFUs/mL could be detected. When the enrichment culture time was 4 h, target bacteria with an initial contamination inoculation volume of 1.5 CFUs/mL could be detected in artificially contaminated samples. The method is fast and highly sensitive, and has not been applied to the detection of V. parahaemolyticus.

Safety and efficacy of ultrasound-guided percutaneous flexor retinaculum release of the ankle: an anatomical study.

Background: Tarsal tunnel syndrome (TTS) is a condition in which the tibial nerve (TN) (or its terminal branches) is compressed by the flexor retinaculum (FR) and the deep fascia of the abductor hallucis muscle at the tarsal tunnel, causing symptoms that negatively impact the patient's quality of life, including numbness, a sensation of a foreign object, coldness, and pain. FR release via microtrauma using needle-knife has proven to be effective in China and is widely used by clinicians. The traditional acupotomy, however, is the "blind knife" treatment, which cannot guarantee patient safety due to risk of injury to important structures, particularly the neurovascular bundle. Compared with the conventional treatments, ultrasound-guided percutaneous FR release possesses noteworthy advantages including high efficacy and safety. Methods: Percutaneous release of the FR was performed on 51 formalin-fixed specimens. The specimens were divided into two groups: an ultrasound-guided acupotomy pushing group comprising 20 legs (group U) and a nonultrasound-guided acupotomy pushing group comprising 31 legs (group N). After high-frequency ultrasound exploration, those with clear vascular imaging were included in group U; otherwise, they were included in group N. The FR was released percutaneously, soft tissue was dissected layer by layer, and anatomical data were recorded. Results: There no cases of injury in group U (0%) and four in group N (12.9%). Among the different intervention methods, there were no significant differences in tissue injury types (χ2=2.80; P=0.09). The percentage of released FR in group U was 80.00% while that in group N was 61.29% (χ2=1.977; P=0.16), which did not represent a significant difference between the two groups. However, group U had a significantly greater release length than that in the group N (t=3.359; P=0.002), indicating that the flexor release length guided by ultrasound is significantly greater than the unguided one. Conclusions: Ultrasound-guided percutaneous release of the FR using a needle-knife can provide greater length and percentage of released FR while maintaining a comparable safety rate to the unguided procedure.

Enhancing Reversibility and Stability of Mg Metal Anodes: High-Exposure (002) Facets and Nanosheet Arrays for Superior Mg Plating/Stripping.

Magnesium metal batteries (MMBs), recognized as promising contenders for post-lithium battery technologies, face challenges such as uneven magnesium (Mg) plating and stripping behaviors, leading to uncontrollable dendrite growth and irreversible structural damage. Herein, we have developed a Mg foil featuring prominently exposed (002) facets and an architecture of nanosheet arrays (termed (002)-Mg), created through a one-step acid etching method. Specifically, the prominent exposure of Mg (002) facets, known for their inherently low surface and adsorption energies with Mg atoms, not only facilitates smooth nucleation and dense deposition but also significantly mitigates side reactions on the Mg anode. Moreover, the nanosheet arrays on the surface evenly distribute the electric field and Mg ion flux, enhancing Mg ion transfer kinetics. As a result, the fabricated (002)-Mg electrodes exhibit unprecedented long-cycle performance, lasting over 6000 h (> 8 months) at a current density of 3 mA cm-2 for a capacity of 3 mAh cm-2. Furthermore, the corresponding pouch cells equipped with various electrolytes and cathodes demonstrate remarkable capacity and cycling stability, highlighting the superior electrochemical compatibility of the (002)-Mg electrode. This study provides new insights into the advancement of durable MMBs by modifying the crystal structure and morphology of Mg.

Impact of earthworms on suppressing dissemination of antibiotic resistance genes during vermicomposting treatment of excess sludge.

Earthworms play a crucial role in suppressing the dissemination of antibiotic resistance genes (ARGs) during vermicomposting. However, there is still a lack of how earthworms influence the spread of ARGs. To address this gap, a microcosm experiment was conducted, incorporating earthworms and utilizing metagenomics and quantitative PCR to assess the impact of earthworms on microbial interactions and the removal of plasmid-induced ARGs. The findings revealed that vermicomposting led to a reduction in the relative abundance of ARGs by altering microbial communities and interactions. Significantly, vermicomposting demonstrated an impressive capability, reducing 92% of ARGs donor bacteria and impeding the transmission of 94% of the RP4 plasmid. Furthermore, through structural equation model analysis, it was determined that mobile genetic elements and environmental variables were the primary influencers of ARG reduction. Overall, this study offers a fresh perspective on the effects of vermicomposting and its potential to mitigate the spread of ARGs.

Availability of family care resources, bathing assistance and toileting assistance among older adults with functional limitations: an evidence-based study from China.

BACKGROUND: An aging population has contributed to an increasing prevalence of functional limitations among older adults. Family support plays a crucial role in toileting and bathing assistance. Yet, the relationship between availability of family care resources and such actual assistance remains insufficiently explored. Our study aims to describe availability of family care resources and identify the association between availability of family care resources and toileting assistance or bathing assistance. METHODS: This study employed a cross-sectional analysis of data from the 2018 National Survey of the China Health and Retirement Longitudinal Study (CHARLS). The availability of family care resources was assessed using measurements of spouse availability, adult child availability, and living arrangement. Bathing assistance and toileting assistance were measured based on self-reported receipt of such assistance. Descriptive statistics were used to depict the overall and subgroup situation of availability of family care resources. Multivariable logistic models were employed to investigate the relationship between availability of family care resources and the receipt of toileting assistance or bathing assistance. RESULTS: Among the sample of older adults with functional limitations, 69% had a spouse, 63% had at least one adult child, and 80% resided with family members. Among those with bathing disability, 13% reported lacking bathing assistance, and among those with toileting disability, 54% reported lacking toileting assistance. Participants with 1-2 adult children had lower odds of receiving toileting assistance (OR: 0.28, 95% CI: 0.09, 0.91, p= 0.034) compared to those with three or more adult children. Spouse availability and living arrangement did not exhibit statistically significant associations with toileting assistance. Participants without a spouse had lower odds of receiving bathing assistance (OR: 0.27, 95% CI: 0.09-0.78, p= 0.016) in comparison to those with a spouse; however, adult child availability and living arrangement did not display statistically significant associations with bathing assistance. CONCLUSION: The present findings suggest a gap in family commitment when it comes to assisting older adults with functional limitations in bathing/toileting. To address this, policymakers are encouraged to prioritize the implementation of proactive mechanisms for identifying family caregivers, alongside incentives to enhance their engagement in practical caregiving activities. Furthermore, it is crucial to emphasize the prioritization of affordable and easily accessible formal toileting/bathing assistance options for older adults who lack sufficient family care resources.

Postoperative cognitive dysfunction in heart transplantation recipients.

OBJECTIVE: This study aimed to investigate the occurrence and risk factors of postoperative neurocognitive disorder (NCD) in patients who underwent heart transplantation. METHODS: Seventy-six heart transplant patients were analyzed for clinical data including gender, age, height, weight, education level, left ventricular ejection fraction (LVEF), stroke volume (SV), transplantation duration, and pretransplant medical history. Cognitive function was assessed using the mini-mental status examination (MMSE) and Montreal cognitive assessment (MoCA) scales. Patients were categorized into cognitively normal and impaired groups based on the presence or absence of cognitive dysfunction, and their cognitive function scores were compared. Multivariate logistic regression was used to identify independent risk factors for cognitive impairment in postoperative cardiac transplant patients. RESULTS: Cognitive dysfunction was observed in 48 out of 76 heart transplant patients, representing an incidence of 63.2%. Cognitive impairment in heart transplant recipients predominantly affected multiple cognitive domains. Logistic regression analysis identified age (OR = 1.057, 95% CI 1.002-1.115), gender (OR = .200, 95% CI .044-.919), education level (OR = .728, 95% CI .600-.883), LVEF (OR = .891, 95% CI .820-.969), and history of diabetes (OR = 7.674, 95% CI 1.317-44.733) as independent risk factors for postoperative NCD in heart transplant recipients (P < .05). CONCLUSION: The study found a high incidence of postoperative NCD in heart transplant patients, with gender, age, education level, LVEF, and diabetes history being significant risk factors. Early identification and intervention targeting these risk factors may help prevent NCD in postheart transplant patients and improve long-term outcomes.

Associations of glyphosate exposure and serum sex steroid hormones among 6-19-year-old children and adolescents.

Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited human evidence was available, especially for children and adolescents. The present study aimed to examine the associations between exposure to glyphosate and sex hormones among participants aged 6-19 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Children and adolescents who had available data on urinary glyphosate, serum sex steroid hormones, including testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG), and covariates were selected. Additionally, the ratio of TT to E2 (TT/E2) and the free androgen index (FAI), which was calculated using TT/SHBG, were also included as sex hormone indicators. Survey regression statistical modeling was used to examine the associations between urinary glyphosate concentration and sex hormone indicators by age and sex group. Among the 964 participants, 83.71% had been exposed to glyphosate (>lower limit of detection). The survey regression revealed a marginally negative association between urinary glyphosate and E2 in the overall population, while this association was more pronounced in adolescents with a significant trend. In further sex-stratified analyses among adolescents, a significant decrease in E2, FAI, and TT (p trend <0.05) was observed in female adolescents for the highest quartile of urinary glyphosate compared to the lowest quartile. However, no similar association was observed among male adolescents. Our findings suggest that exposure to glyphosate at the current level may decrease the levels of sex steroids in adolescents, particularly female adolescents. Considering the cross-sectional study design, further research is needed to confirm our findings.

Nontargeted Analysis of Coumarins in Source Water and Their Formation of Chlorinated Coumarins as DBPs in Drinking Water.

Coumarin was detected as one of the most abundant compounds by nontargeted analysis of natural product components in actual water samples prior to disinfection. More importantly, prechlorination of humic acid generated 3-hydroxycoumarin and monohydroxy-monomethyl-substituted coumarin with a total yield of ≤10.1%, which suggested the humic substance in raw water is an important source of coumarins. 7-Hydroxycoumarin, 6-hydroxy-4-methylcoumarin, 6,7-dihydroxycoumarin, and 7-methoxy-4-methylcoumarin were identified in raw water by high-performance liquid chromatography-tandem high-resolution mass spectrometry because only some coumarin standards were commercially available. Their chlorination generated monochlorinated and polychlorinated coumarins, and their structures were confirmed by the synthesized standards. These products could form at various dosages of chlorine and pH levels, and some with a concentration of 600 ng/L can be stable in tap water for days. 3,6,8-Trichloro-7-hydroxycoumarin, 3-chloro-7-methoxy-4-methylcoumarin, and 3,6-dichloro-7-methoxy-4-methylcoumarin were first identified in finished water with concentrations of 0.0670, 78.1, and 14.7 ng/L, respectively, but not in source water, suggesting that they are new DBPs formed during disinfection. The cytotoxicity of 3-chloro-7-methoxy-4-methylcoumarin in CHO-K1 cells was comparable to those of 2,6-dibromo-1,4-benzoquinone and 2,6-dichloro-1,4-benzoquinone in TIC-Tox analyses, suggesting that further investigation of their occurrence and control in drinking water systems is warranted.

Metabolites and metabolic pathway analysis of sulfadimidine in carp (Cyprinus carpio) based on UHPLC-Q-orbitrap HRMS.

Sulfadimidine (SM2) is an N-substituted derivative of p-aminobenzenesulfonyl structure. This study aimed to analyze the metabolism of SM2 in carp (Cyprinus carpio). The carps were fed with SM2 at a dose of 200 mg/(kg · bw) and then killed. The blood, muscle, liver, kidney, gill, other guts, and carp aquaculture water samples were collected. The UHPLC-Q-Exactive Plus Orbitrap-MS was adopted for determining the metabolites of SM2 in the aforementioned samples. Twelve metabolites, which were divided into metabolites in vivo and metabolites in vitro, were identified using Compound Discoverer software. The metabolic pathways in vivo of SM2 in carp included acetylation, hydroxylation, glucoside conjugation, glycine conjugation, carboxylation, glucuronide conjugation, reduction, and methylation. The metabolic pathways in vitro included oxidation and acetylation. This study clarified the metabolites and metabolic pathways of SM2 in carp and provided a reference for further pharmacodynamic evaluation and use in aquaculture.

Wide temperature adaptive oxidase-like based on mesoporous manganese based metal-organic framework for detecting total antioxidant capacity.

Overcoming the intense variation of enzymatic activity among different temperatures is very critical in catalytic medicine and catalytic biology. Here, Mn-based metal-organic framework-based wide-temperature-adaptive mesoporous artificial enzymes (Mn-TMA-MOF) were designed and synthesized. The oxidase-like Mn-TMA-MOF showed excellent catalytic activity at 0-50 °C and avoided the activity loss and instability due to temperature variation that occurred. The excellent oxidase-like properties of Mn-TMA-MOF with wide temperature adaptativeness are mainly ascribed to the mixed oxidized state (Mn3+/Mn2+) and high substrate affinity (Km = 0.034 mM) of Mn. Moreover, the mesopore-micropores two-level structure of Mn-TMA-MOF provides a large space and surface area for enzyme catalysis. Based on the stability of Mn-TMA-MOF, we developed a colorimetric sensor that can detect total antioxidant capacity in fruits with a limit of detection up to 0.59 µM.

Seasonal and distance-decay patterns of surface sediments microbial nitrogen and sulfur cycling linkage in the eastern coast of China.

The surface sediments as a repository of pelagic environment changes and microbial community structural succession tend to have a profound effect on global and local nitrogen and sulfur cycling. In this study, analysis of sediment samples collected from the Bohai Sea, Yellow Sea, and north of the East China Seas (BYnECS) revealed longitude, latitude, depth, and chlorophyll had the strongest influence on microbial community structure (p-values < 0.005). A clear distance-decay pattern was exhibited in BYnECS. The result of co-occurrence network modularization implied that the more active pathway in winter was thiosulfate reduction and nitrate reduction, while in summer it was nitrification. The potential functional genes were predicted in microbial communities, and the most dominant genes were assigned to assimilatory sulfur reduction, denitrification, and dissimilatory nitrate reduction. This study innovatively explored the potential relationships between nitrogen and sulfur cycling genes of these three sea regions in the China Sea.

A novel ZIF-L/PEI thin film nanocomposite membrane for removing perfluoroalkyl substances (PFASs) from water: Enhanced retention and high flux.

Membrane separation technology is widely recognized as an effective method for removing perfluoroalkyl substances (PFASs) in water treatment. ZIF-L, a metal-organic framework (MOF) family characterized by its mat-like cavities and leaf-like morphology, has garnered considerable interest and has been extensively employed in fabricating thin-film nanocomposite (TFN) membranes. In this study, a robust, high-performance TFN membrane to remove PFASs in a nanofiltration (NF) process was created through an interfacial polymerization approach on the surface of polysulfone (PSF), incorporating ZIF-L within the selective layer. The TFN membrane modified by adding 5 wt% ZIF-L (relative to the weight of ethylene imine polymer (PEI)) exhibits 2.3 times higher water flux (up to 47.56 L·m-2·h-1·bar-1) than the pristine thin film composite membrane (20.46 L·m-2·h-1·bar-1), and the rejection for typical PFASs were above 95 % (98.47 % for perfluorooctanesulfonic acid (PFOS) and 95.85 % for perfluorooctanoic acid (PFOA)). The effectiveness of the ZIF-L/PEI TFN membrane in retaining representative PFASs was examined under various conditions, including different pressures, feed concentrations, aqueous environments, and salt ions. Notably, the experiments demonstrated that even after contamination with humic acid (HA), >88 % of the water flux could be restored by washing. Additionally, density functional theory (DFT) calculations were employed to predict the distinct intermolecular interactions between PFASs and ZIF-L as well as PEI. These calculations provide additional insights into the interception mechanism of TFN membranes towards PFASs. Based on this study, TFN membranes incorporating MOF as nanofillers show great potential as an effective method for purifying PFASs from aqueous environments and possess superior environmental sustainability and cost-effectiveness.

A cross-sectional study: caregiver burden and related determinants of adult patients with ß-thalassemia major in mainland China.

BACKGROUND: The informal caregivers of adult patients with ß-thalassemia major (ß-TM) bear not only physical but also emotional and economic pressures of providing care. This study is the first to evaluate the caregiver burden by Zarit Burden Interview (ZBI) of adult patients with ß-TM in mainland China and to identify predictors of caregiver burden. METHODS: In this cross-sectional study, we conducted an online survey with snowball sampling covering seven provinces between September 1, 2021, and January 31, 2022, of patients aged ≥ 18 years with ß-TM and their informal caregivers. Caregiver burden was assessed using the ZBI. Data on patient demographics, disease and therapy characteristics, and informal caregivers' demographic characteristics were collected and analysed using independent t-tests, analysis of variance, Spearman's correlation and multiple linear regression. RESULTS: Of 75 included patients, more than half (50.7%) were male. The mean patient age was 24.69 ± 5.59 years. The mean age of the informal caregivers was 50.60 ± 9.16 years, with women (74.7%) being predominant. The ZBI score was 38.00 ± 17.02. Multiple linear regression analysis showed that patients with interrupted blood transfusion therapy and informal caregivers required to care of others were positively associated with caregiver burden (p < 0.05). Age of informal caregivers were borderline significant positively associated with caregiver burden (p < 0.1). Married informal caregivers were negatively associated with caregiver burden (p < 0.05). CONCLUSIONS: The informal caregivers of adult patients with ß-TM in mainland China experienced a moderate-to-severe level of caregiving burden. The caregiver burden was higher in patients with a history of interrupted blood transfusion therapy or in informal caregivers who were older or needed to care for others. Additionally, married informal caregivers experienced lower burdens compared to non-married informal caregivers. These findings provide a reference to identify informal caregivers with higher burdens among patients with ß-TM.

Thermo-sensitive hydroxybutyl chitosan/diatom biosilica hydrogel with immune microenvironment regulatory for chronic wound healing.

This study proposes a chronic wound therapeutic strategy based on extracellular matrix (ECM) biomimetics and immune regulation. The hydroxybutyl chitosan/diatom biosilica hydrogel (H/D) which can regulate the immune microenvironment, is prepared from hydroxybutyl chitosan (HBC) as matrix to construct the bionic ECM and diatom biosilica (DB) as structural active unit. The hierarchical porous structure of DB provides strong anchoring interface effect to enhance the mechanical strength of hydrogel, while maintaining its favorable temperature phase transition behavior, improving the material's fit to the wound and convenience of clinical use. Silicates released from DB in H/D accelerate the transition of wounds from inflammation to proliferation and remodeling. In cellular and diabetic rat models, H/D reduces inflammation (induces conversion of M1-type macrophages to M2-type), induces angiogenesis (1.96-fold of control), promotes fibroblast proliferation (180.36 % of control), collagen deposition, keratinocyte migration (47.34 % more than control), and re-epithelialization. This study validates a possible biological mechanism for H/D bioactive hydrogel-mediated regulation of the immune microenvironment and provides a simple synergistic dressing strategy.

Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1.

BACKGROUND: Hexokinase I (HK1) is highly expressed in a variety of malignancies, regulates glycolytic pathway in cancer cells, and thus considered to be one of the promising molecular targets for cancer therapy. Nonetheless, the development of a specific inhibitor against HK1 remains elusive. PURPOSE: This study aims to elucidate the mechanism by which oridonin inhibits the proliferation and immune evasion of bladder cancer cells, specifically through the suppression of HK1. METHODS: To examine the mechanisms by which oridonin directly binds to cysteines of HK1 and inhibits bladder cancer growth, this study utilized a variety of methods. These included the Human Proteome Microarray, Streptavidin-agarose affinity assay, Biolayer Interferometry (BLI) ainding analysis, Mass Spectrometry, Cellular Thermal Shift Assay, Extracellular Acidification Rate measurement, and Xenotransplant mouse models. RESULTS: As indicated by our current findings, oridonin forms a covalent bond with Cys-813, located adjacently to glucose-binding domain of HK1. This suppresses the enzymatic activity of HK1, leading to an effective reduction of glycolysis, which triggers cell death via apoptosis in cells derived from human bladder cancer. Significantly, oridonin also inhibits lactate-induced PD-L1 expression in bladder cancer. Furthermore, pairing oridonin with a PD-L1 inhibitor amplifies the cytotoxicity of CD8+ T cells against bladder cancer. CONCLUSION: This research strongly suggests that oridonin serves as a covalent inhibitor of HK1. Moreover, it indicates that functional cysteine residue of HK1 could operate as viable targets for selective inhibition. Consequently, oridonin exhibits substantial potential for the evolution of anti-cancer agents targeting the potential therapeutic target HK1 via metabolism immunomodulation.

Preference for primary care in Chinese homebound patients.

OBJECTIVE: This study aims to describe the preference for primary healthcare (PHC) and investigate associated factors among homebound residents in both rural and urban areas of China. It provides valuable insights to facilitate the rational allocation of healthcare resources and promote the utilization of PHC. METHODS: In this nationally representative cross-sectional study, we utilized the most recent data (2020) from the China Family Panel Studies (CFPS). Participants were recruited from 25 provincial-level administrative regions in both rural and urban areas of China. Homebound patients were asked to provide details about their individual characteristics, variables related to family caregiving, and preferences for PHC. Multivariable logistic models were used to analyze potential factors associated with preference for PHC. Estimates of association were reported as odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: The study found that 58.43% of rural patients reported a preference for PHC, while 42.78% of urban patients favored PHC. Compared to rural participants who did not received inpatient care in the past year, those who received inpatient care in the past year had 67% lower odds of choosing PHC (OR:0.33, 95% CI:0.19-0.59); Compared to rural participants who did not received family caregiving when ill, those who received family caregiving when ill had 59% lower odds of choosing PHC (OR: 0.41, 95% CI:0.21-0.77). Correspondingly, Compared to urban participants who did not received inpatient care in the past year, those who had received inpatient care in the past year had 75% lower odds of choosing PHC (OR: 0.25, 95% CI: 0.10-0.56); Compared to urban participants who did not received family caregiving when ill, those who received family caregiving when ill had 73% lower odds of choosing PHC (OR: 0.27, 95% CI: 0.11-0.63); Compared to urban participants who with agricultural Hukou, those with Non-agricultural Hukou had 61% lower odds of choosing PHC (OR: 0.39, 95% CI:0.18-0.83); Compared to urban participants living in the eastern part of mainland China, those living in the central part of China had 188% higher odds of choosing PHC (OR: 2.88, 95% CI: 1.14-7.29). CONCLUSION: Policymakers should focus on tailoring PHC to vulnerable populations and prioritizing family-based public health strategies for enhancing homebound patients' perceptions of PHC. Furthermore, further study is needed on whether the Hukou registration system affects the barriers that homebound patients experience in choosing healthcare providers.