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1.
Acta Diabetol ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833006

ABSTRACT

AIMS: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene-gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM). METHODS: SNPstats online software ( https://www.snpstats.net/start.htm ) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus ( http://shesisplus.bio-x.cn/SHEsis.html ) online software was used for haplotype analysis. RESULTS: A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13-2.01), 1.44 (1.10-1.89) and 1.25 (1.01-1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18-0.79) and 0.37 (0.16-0.80) for codominant and recessive models, respectively. No significant gene-gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68-0.98), P = 0.047. CONCLUSIONS: Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.

2.
Poult Sci ; 103(6): 103740, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701629

ABSTRACT

Meat quality traits are essential for producing high-quality broilers, but the genetic improvement has been limited by the complexity of measurement methods and the numerous traits involved. To systematically understand the meat quality characteristics of different broiler breeds, this study collected data on slaughter performance, skin color, fat deposition, and meat quality traits of 434 broilers from 12 different breeds in South China. The results showed that there was no significant difference in the live weight and slaughter weight of various broiler breeds at their respective market ages. Commercial broiler breeds such as Xiaobai and Huangma chickens had higher breast muscle and leg muscle rates. The skin and abdominal fat of Huangma chickens cultivated in the consumer market in South China exhibited significantly higher levels of yellowness compared to other varieties. Concerning fat traits, we observed that Wenchang chickens exhibited a strong ability to fat deposition, while the younger breeds showed lower fat deposition. Additionally, there were significant positive correlations found among different traits, including traits related to weight, traits related to fat, and skin color of different parts. Hierarchical clustering analysis revealed that fast-growing and large broiler Xiaobai chickens formed a distinct cluster based on carcass characteristics, skin color, and meat quality traits. Principal component analysis (PCA) was used to extract multiple principal components as substitutes for complex meat quality indicators, establishing a chicken meat quality evaluation model to differentiate between different breeds of chickens. At the same time, we identified 46, 22, and 20 SNP loci and their adjacent genes that were significantly associated with muscle mass traits, fat deposition, and skin color through genome-wide association studies (GWAS). The above results are helpful for systematically understanding the differences and characteristics of meat quality traits among different breeds.


Subject(s)
Chickens , Meat , Animals , Chickens/genetics , Chickens/physiology , Meat/analysis , Meat/standards , China , Male
3.
Inflammation ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691250

ABSTRACT

Periodontitis, an infectious inflammatory disease influenced by various factors, disrupts the delicate balance between the host microbiota and immunity. The resulting excessive immune response exacerbates the progressive destruction of the supporting periodontal tissue. Macrophages are essential elements of the host innate immune system. They are pivotal components in the periodontal immune microenvironment and actively participate in both physiological and pathological processes of periodontal tissue. When confronted with periodontitis-related irritant factors, macrophages may differentiate to pro- or anti-inflammatory subtypes that affect tissue homeostasis. Additionally, macrophages may die in response to bacterial infections, potentially affecting the severity of periodontitis. This article reviews the typical mechanisms underlying macrophage death and its effects on periodontitis. We describe five forms of macrophage death in periodontitis: apoptosis, pyroptosis, necroptosis, ferroptosis, and ETosis. Our review of macrophage death in the pathophysiology of periodontitis enhances comprehension of the pathogenesis of periodontitis that will be useful for clinical practice. Although our review elucidates the complex mechanisms by which macrophage death and inflammatory pathways perpetuate periodontitis, unresolved issues remain, necessitating further research.

4.
Chin J Traumatol ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38762419

ABSTRACT

PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95 % CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95 % CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95 % CI: -2.81 - -0.18), p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95 % CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95 % CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95 % CI: -1.64 - -0.52, p = 0.002). CONCLUSION: In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.

5.
World J Gastroenterol ; 30(19): 2612-2614, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38817654

ABSTRACT

Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate between the two conditions. However, examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process. It may serve as a valuable tool in distinguishing GERD from FHB.


Subject(s)
Gastroesophageal Reflux , Heartburn , Pepsin A , Saliva , Humans , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/microbiology , Saliva/microbiology , Heartburn/diagnosis , Heartburn/etiology , Pepsin A/analysis , Pepsin A/metabolism , Diagnosis, Differential , Biomarkers/analysis , Biomarkers/metabolism
6.
Poult Sci ; 103(7): 103863, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38810566

ABSTRACT

The introduction of exotic breeds and the cultivation of new lines by breeding companies have posed challenges to native chickens in South China, including loss of breed characteristics, decreased genetic diversity, and declining purity. Understanding the population genetic structure and genetic diversity of native chickens in South China is crucial for further advancements in breeding efforts. In this study, we analyzed the population genetic structure and genetic diversity of 321 individuals from 10 different breeds in South China. By comparing commercial chickens with native ones, we identified selection signatures occurring between local chickens and commercial breeds. The analysis of population genetic structure revealed that the native chicken populations in South China exhibited a considerable level of genetic diversity. Moreover, the commercial lines of Xiaobai chicken and Huangma chicken displayed even higher levels of genetic diversity, which distinguished them from other native varieties at the clustering level. However, certain individuals within these commercial varieties showed a discernible genetic relationship with the native populations. Notably, both commercial varieties also retained a significant degree of genetic similarity to their respective native counterparts. In order to investigate the genomic changes occurring during the commercialization of native chickens, we employed 4 methods (Fst, ROD, XPCLR, and XPEHH) to identify potential candidate regions displaying selective signatures in Southern Chinese native chicken population. A total of 168 (identified by Fst and ROD) and 86 (identified by XPCLR and XPEHH) overlapping genes were discovered. Functional annotation analysis revealed that these genes may be associated with reproduction and growth (SAMSN1, HYLS1, ROBO3, FGF14, PRSS23), musculoskeletal development (DNER, MYBPC1, DGKB, ORC1, KLF10), disease resistance and environmental adaptability (PUS3, CRB2, CALD1, USP15, SGCD, LTBP1), as well as egg production (ADGRB3, ACSF3). Overall, native chickens in South China harbor numerous selective sweep regions compared to commercial chickens, enriching valuable genomic resources for future genetic research and breeding conservation.

7.
Chin J Traumatol ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38811319

ABSTRACT

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION: Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.

8.
Angew Chem Int Ed Engl ; : e202406292, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780997

ABSTRACT

Aqueous Zn-ion batteries are an attractive electrochemical energy storage solution for their budget and safe properties. However, dendrites and uncontrolled side reactions in anodes detract the cycle life and energy density of the batteries.Grain boundaries in metals are generally considered as the source of the above problems but we present a diverse result. This study introduces an ultra-high proportion of grain boundaries on zinc electrodes through femtosecond laser bombardment to enhance stability of zinc metal/electrolyte interface.The ultra-high proportion of grain boundaries promotes the homogenization of zinc growth potential, to achieve uniform nucleation and growth, thereby suppressing dendrite formation. Additionally, the abundant active sites mitigate the side reactions during the electrochemical process. Consequently, the 15-µm-Fs-Zn||MnO2 pouch cell achieves an energy density of 249.4 Wh kg-1 and  operates for over 60 cycles at a depth-of-discharge of 23%. The recognition of the favorable influence exerted by UP-GBs paves a new way for other metal batteries.

9.
Zhen Ci Yan Jiu ; 49(5): 463-471, 2024 May 25.
Article in English, Chinese | MEDLINE | ID: mdl-38764117

ABSTRACT

OBJECTIVES: To observe the effect of electro-scalp acupuncture (ESA) on the expression of cytochrome P450a1/b1 (CYP27a1/b1), cytochrome P45024a (CYP24a), signal transducer and activator of transcription (STAT)4, STAT6, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-4 in ischemic cerebral cortex of rats with acute ischemic stroke, so as to explore its mechanism in alleviating inflammatory reaction of ischemic stroke. METHODS: Sixty SD rats were randomly divided into sham-operation, model, vitamin D3 and ESA groups, with 15 rats in each group. The middle cerebral artery occlusion rat model was established with thread ligation according to Zea-Longa's method. Rats in the vitamin D3 group were given 1, 25-VitD3 solution (3 ng·100 g-1·d-1) by gavage, once daily for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. TTC staining was used to detect the volume of cerebral infarction in rats. The positive expressions of CYP24a, CYP27a1 and CYP27b1 in the cerebral cortex of ischemic area were detected by immunofluorescence. The mRNA expressions of STAT4 and STAT6 in the cerebral cortex of ischemic area were detected by quantitative real-time PCR. The protein expression levels of TNF-α, IL-1ß and IL-4 in the cerebral cortex of ischemic area were detected by Western blot. RESULTS: Compared with the sham-operation group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were increased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA, protein expression level of IL-4 were decreased (P<0.01) in the model group. After the treatment and compared with the model group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were decreased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA expression level, protein expression level of IL-4 were increased (P<0.01) in the ESA and vitamin D3 groups. CONCLUSIONS: ESA can alleviate the inflammatory response in ischemic stroke, which maybe related to its function in regulating the balance between CYP27a1/b1 and CYP24a, converting vitamin D into active vitamin D3, inhibiting vitamin D3 degradation, and regulating Th1/Th2 balance.


Subject(s)
Infarction, Middle Cerebral Artery , Vitamin D3 24-Hydroxylase , Animals , Humans , Male , Rats , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism , Acupuncture Points , Brain Ischemia/therapy , Brain Ischemia/metabolism , Brain Ischemia/genetics , Cerebral Cortex/metabolism , Cholestanetriol 26-Monooxygenase/genetics , Cholestanetriol 26-Monooxygenase/metabolism , Cytokines/metabolism , Cytokines/genetics , Electroacupuncture , Infarction, Middle Cerebral Artery/therapy , Infarction, Middle Cerebral Artery/genetics , Infarction, Middle Cerebral Artery/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-4/genetics , Interleukin-4/metabolism , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Vitamin D3 24-Hydroxylase/genetics , Vitamin D3 24-Hydroxylase/metabolism
10.
Infection ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38652225

ABSTRACT

PURPOSE: Physicians may administer Nirmatrelvir-ritonavir to patients who have been symptomatic for more than 5 days. There is currently no clear evidence to support this approach. METHODS: A real-world study was conducted to investigate the potential relationship between the administration of Nirmatrelvir-ritonavir and the rates of intubation or in-hospital mortality among COVID-19 patients who experienced symptoms for more than 5 days. The end point was a composite event of intubation or in-hospital mortality. The outcomes between those patients who received Nirmatrelvir-ritonavir and those who did not were compared. RESULTS: A total of 847 patients were included in the analysis. Among them, 312 patients (36.84%) received Nirmatrelvir-ritonavir. Within the entire population, 86 patients (10.15%) experienced intubation or in-hospital mortality. The main analysis indicated that there was a significant association between the application of Nirmatrelvir-ritonavir and intubation or in-hospital mortality, with an odds ratio of 0.50 (95% confidence interval, 0.28 to 0.87; P = 0.0153) using inverse probability of treatment weighting. The finding was consistent with multiple sensitivity analyses. CONCLUSIONS: The application of Nirmatrelvir-ritonavir was associated with a significantly reduced risk of intubation or death in hospitalized COVID-19 patients who experienced symptoms for more than 5 days as compared to those who did not receive the treatment.

11.
World J Gastrointest Oncol ; 16(4): 1361-1373, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38660655

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

12.
Small Methods ; : e2301645, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607956

ABSTRACT

Bimetallic phosphides are considered as promising electrocatalysts for zinc-air batteries toward oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). To address the semi-conductor inherent low electronic conductivity and catalytic activity, a polymetal-chelated strategy is employed to in situ fabricate bimetallic nanophosphides within carbon matrix anchoring by chemical bonding. The employment of biomolecule polydopamine (PDA) efficiently anchors various transition metal ions due to its strong chelating capability via inherent functional groups. Furthermore, the chelation of multi-metal ion is proved to promote the formation of graphitic nitrogen. The bimetallic FexCoyP phosphides nanoparticles are intimately encapsulated in carbon matrix through in situ carbonization and phosphatization processes. When utilized in Zinc-air batteries, Fe0.20Co0.80P anchored within N, P co-doped sub-microsphere (Fe0.20Co0.80P /PNC) exhibit a maximum power density of 167 mW cm-2 and cycle life up to 270 cycles, with a round-trip voltage of 0.955 V. The mechanisms for catalytic activity passivation are ascribed to the etching of nitrogen and oxidation of phosphorus in carbon matrix, as well as the oxidation of the surface phosphide on the sub-microspheres. This study presents a promising candidate for advancing the further development of energy conversation catalysis.

13.
J Gastrointest Surg ; 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38616463

ABSTRACT

BACKGROUND: Gastric cancer (GC), considered the fifth most prevalent malignancy, is the fourth leading cause of cancer death worldwide. This cancer is heterogeneous and invasive and often metastasizes to the liver. The survival of patients with GC, especially cancer-specific survival (CSS), is a matter of concern to their families and medical workers in clinical practice. However, efficient tools for early risk prediction are lacking. Thus, this study aimed to develop a nomogram for forecasting the overall survival (OS) and CSS of patients with GC with liver metastasis (GCLM) based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Information on individuals with GCLM was acquired from the SEER database from January 2000 to December 2015. Patients' data were randomized into the train cohort and the test cohort. The independent factors for CSS and OS were determined by univariate and multivariate competing risk analyses and Cox proportional hazards analysis, and the nomograms for predicting CSS and OS were constructed. The receiver operating characteristic curve and calibration curve were used to measure the accuracy and calibration of nomograms. RESULTS: Our study included 4372 patients with GCLM, with 3060 patients in the train set and 1312 in the test set. The mean follow-up period was 12.31 months. The independent factors influencing the OS of patients with GCLM were age, bone metastasis, chemotherapy, grade, lung metastasis, stage, primary site, radiotherapy, surgical primary site, T stage, and tumor size. The concordance Index (C-index) of the constructed nomogram for OS were 0.718 (SE, 0.004) in the train set and 0.0.680 (SE, 0.006) in the test set. The independent factors affecting the CSS of patients with GCLM were age, chemotherapy, grade, lung metastasis, stage, radiotherapy, regional lymph node positive, surgical primary site, and total number of tumors. The C-index for the constructed nomogram for CSS were 0.696 (SE, 0.005) in the train set and 0.696 (SE, 0.008) in the test set. CONCLUSION: The constructed nomograms showed satisfactory performance in predicting the OS and CSS of patients with GCLM, which can help clinicians formulate follow-up and rehabilitation strategies conducive to survival. At the same time, it can provide more family and social support for high-risk groups.

14.
Res Sq ; 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38562709

ABSTRACT

Background: Variants in the CTSB gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson's disease (PD). However, neither the specific CTSB variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis. Previous in vitro studies have found that catB can cleave monomeric and fibrillar alpha-synuclein, a key protein involved in the pathogenesis of PD that accumulates in the brains of PD patients. However, truncated synuclein isoforms generated by catB cleavage have an increased propensity to aggregate. Thus, catB activity could potentially contribute to lysosomal degradation and clearance of pathogenic alpha synuclein from the cell, but also has the potential of enhancing synuclein pathology by generating aggregation-prone truncations. Therefore, the mechanisms linking catB to PD pathophysiology remain to be clarified. Methods: Here, we conducted genetic analyses of the association between common and rare CTSB variants and risk of PD. We then used genetic and pharmacological approaches to manipulate catB expression and function in cell lines and induced pluripotent stem cell-derived dopaminergic neurons and assessed lysosomal activity and the handling of aggregated synuclein fibrils. Results: We first identified specific non-coding variants in CTSB that drive the association with PD and are linked to changes in brain CTSB expression levels. Using iPSC-derived dopaminergic neurons we then find that catB inhibition impairs autophagy, reduces glucocerebrosidase (encoded by GBA1) activity, and leads to an accumulation of lysosomal content. Moreover, in cell lines, reduction of CTSB gene expression impairs the degradation of pre-formed alpha-synuclein fibrils, whereas CTSB gene activation enhances fibril clearance. Similarly, in midbrain organoids and dopaminergic neurons treated with alpha-synuclein fibrils, catB inhibition or knockout potentiates the formation of inclusions which stain positively for phosphorylated alpha-synuclein. Conclusions: The results of our genetic and functional studies indicate that the reduction of catB function negatively impacts lysosomal pathways associated with PD pathogenesis, while conversely catB activation could promote the clearance of pathogenic alpha-synuclein.

15.
J Oral Microbiol ; 16(1): 2344278, 2024.
Article in English | MEDLINE | ID: mdl-38686186

ABSTRACT

Background: Tongue coating microbiota has aroused particular interest in profiling oral and digestive system cancers. However, little is known on the relationship between tongue coating microbiome and colorectal cancer (CRC). Methods: Metagenomic shotgun sequencing was performed on tongue coating samples collected from 30 patients with CRC, 30 patients with colorectal polyps (CP), and 30 healthy controls (HC). We further validated the potential of the tongue coating microbiota to predict the CRC by a random forest model. Results: We found a greater species diversity in CRC samples, and the nucleoside and nucleotide biosynthesis pathway was more apparent in the CRC group. Importantly, various species across participants jointly shaped three distinguishable fur types.The tongue coating microbiome profiling data gave an area under the receiver operating characteristic curve (AUC) of 0.915 in discriminating CRC patients from control participants; species such as Atopobium rimae, Streptococcus sanguinis, and Prevotella oris aided differentiation of CRC patients from healthy participants. Conclusion: These results elucidate the use of tongue coating microbiome in CRC patients firstly, and the fur-types observed contribute to a better understanding of the microbial community in human. Furthermore, the tongue coating microbiota-based biomarkers provide a valuable reference for CRC prediction and diagnosis.

17.
ChemSusChem ; : e202400359, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38687195

ABSTRACT

The escalating focus on environmental concerns and the swift advancement of eco-friendly biodegradable batteries raises a pressing demand for enhanced material design in the battery field. The traditional polypropylene (PP) that is monopolistically utilized in the commercial LIBs is hard to recycle. In this work, we prepare a novel water degradable separators via the cross-linking of polyvinyl alcohol (PVA) and dibasic acid (tartaric acid, TA). Through the integration of non-solvent liquid-phase separation, we successfully produced a thermally stable PVA-TA membrane with tunable thickness and a high level of porosity. These specially engineered PVA-TA separators were implemented in LiFePO4 (LFP)|separator|Li cells, resulting in superior multiplicative performance and achieving a capacity of 88 mAh g-1 under 5 C. Additionally, the straightforward small molecule cross-linking technique significantly reduced the crystalline region of the polymer, thereby enhancing ionic conductivity. Notably, after cycling, the PVA-TA separators can be easily dissolved in 95 °C hot water, enabling its reutilization for the production of new PVA-TA separators. Therefore, this work introduces a novel concept to design green and sustainable separators for recyclable lithium batteries.

18.
World J Gastroenterol ; 30(10): 1420-1430, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38596496

ABSTRACT

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.


Subject(s)
Choledochal Cyst , Humans , Female , Rats , Animals , Choledochal Cyst/surgery , Reproducibility of Results , Rats, Sprague-Dawley , Models, Animal , Dilatation, Pathologic , Bilirubin , Disease Models, Animal
19.
Medicine (Baltimore) ; 103(12): e37520, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38518036

ABSTRACT

Oral behavior management methods include basic behavior management methods and drug behavior management methods. In many cases, dental treatment that cannot be done simply through basic behavior management is not possible. The uncooperative behavior of children with dental fear in oral treatment has increased the demand for medication based behavior management methods. Drug sedation can provide more effective analgesic and anti-anxiety effects, thereby helping to provide comfortable, efficient, and high-quality dental services. This article will review the drug sedation methods selected in clinical treatment of pediatric dental fear in recent years, as well as the safety and effectiveness of commonly used drugs, in order to provide guidance for dental professionals in clinical practice.


Subject(s)
Anesthesia, Dental , Anesthesia , Anti-Anxiety Agents , Child , Humans , Dental Anxiety/drug therapy , Dental Anxiety/prevention & control , Behavior Therapy , Conscious Sedation
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