ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Apurinic/apyrimidinic endonuclease 1(APE 1)is a multifunctional protein that plays important roles in DNA repair and regulation of gene expression.Because APE 1 is overexpressed in various cancers,it can serve as a cancer biomarker for aiding clinical diagnosis,guiding therapy,and monitoring prognosis.On this basis,a label-free fluorescent probe was designed based on the primer exchange reaction(PER)strategy for highly sensitive detection of APE 1 activity.In the absence of APE 1,the structure of catalytic hairpin(HP)was stable and could not form G-quadruplex.Therefore,the background fluorescence of this sensing system was very low due to the dissociation of thioflavin T(ThT).In the presence of APE 1,the apurinic/apyrimidinic(AP)site of HP was cleaved by APE 1 and a short nucleic acid fragment that acted as a primer to initiate PER was generated.After PER reaction,a large number of G-quadruplex were produced,which could specifically bind with ThT and resulted in significant increase of fluorescence signal.The combination of low background design of HP and PER amplification made this biosensor had high sensitivity with a detection limit(3σ)of 0.0008 U/mL.Furthermore,the primer sequence was directly generated by the cleavage of APE 1 without additional addition,which not only increased the specificity of the reaction,but also simplified the experiment procedure.Moreover,the use of label-free fluorescence signal reduced the cost of the experiment,and realized rapid detection of APE 1.Finally,this sensor was used to detect APE 1 in human serum samples with spiked recoveries of 91%-104%,proving great potential in study of biological enzyme.

This study aimed to address the limitations of current diagnostic methods for well leg compartment syndrome(WLCS),including invasiveness,high costs,and insufficient accuracy,by proposing a solution based on electrical impedance tomography(EIT)technology.The electrical response characteristics of the human calf muscle to changes in compartment pressure using EIT were investigated,aiming to visualize the effects of pressure variations on the electrical properties within the compartment and to provide technical support for early non-invasive detection of WLCS.EIT sensors were placed on the right calf of the experimental subjects,with pressure applied externally to the right thigh.Measurements were conducted in two phases:pre-pressure(pre)and post-pressure(post).Pre-pressure,the conductivity distribution image σpre was measured when the calf was placed horizontally.Post-pressure,the calf was raised at an angle of approximately 30°,and pressures of 0,40,80,and 120 mmHg were applied to the right thigh,and the corresponding conductivity distribution images σP=0,σP=40,σP=80,andσP=120were recorded.To quantitatively analyze the pressure effects on the compartment response,paired sample t-test was used to assess the spatial-mean conductivity((σ))from the EIT reconstructed images.Compared to the horizontal position of the right calf,raising the calf at approximately 30° resulted in a significant increase in the spatial-mean conductivity(σ)of the M1 compartment.Furthermore,when pressure was applied to the right thigh while the calf remained at a 30° angle,the spatial-mean conductivity of the M1 compartment σM1 showed an increasing trend with rising pressure.The results indicated that as compartment pressure increased,the volume of extracellular fluid and ion concentration significantly increased,leading to an increase in conductivity,which reflected ischemia and hypoxia in muscle tissue and the related pathophysiological changes.EIT,due to its high sensitivity to conductivity changes,offered a potential effective diagnostic method for non-invasively monitoring the onset and progression of muscle compartment syndrome.

Glioma is the most common malignancy of the central nervous system, originating mainly from glial cells. Because of its highly aggressive nature, glioma has one of the highest rates of death among all types of cancer. Therefore, it is very important to develop new therapeutic approaches and drugs for glioma treatment. Instead of activate the telomerase, approximately 30% of glioma use alternative lenthening of telomere (ALT) to maintain telomere length. The mechanism of ALT development is poorly understood, however, some genetic mutations have been reported to induce the development of ALT glioma, such as ATRX, IDH1, p53, etc. The lack of ALT glioma cell lines and preclinical ALT glioma models has limited the mechanistic studies of ALT glioma. Therefore, this review listed ALT glioma cell lines that derived from primary culture or gene editing in the last decade, as well as the xenografted animal models established by ALT glioma cell lines, and discussed the role and significance these cell and animal models play in preclinical studies.

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy* ; Leukemia, Promyelocytic, Acute/therapy* ; Prognosis ; Myelodysplastic Syndromes/drug therapy* ; Neoplasms, Second Primary/drug therapy* ; Remission Induction ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

The evaluation of germplasm resources is the prerequisite for the development, utilization, and conservation of Chinese medicinal resources. The selection of excellent germplasm is the key to the breeding and orderly production of Pinellia ternata. In this study, 21 germplasm materials of P. ternata from major production areas in China were collected and analyzed for population diversity after phenotypic preliminary screening. The results have revealed that the P. ternata population has abundant phenotypic variation, and the phenotypic changes could be divided into five phenotypes in terms of organ trait variation. Further analysis of variation in 20 quantitative traits of the population revealed that the coefficient of variation for adenosine content(339.05%) was the largest, while the coefficient of variation for the underground plant height(16.35%) was the smallest. Correlation analysis showed that there was a strong correlation among various traits, with 52 pairs of traits showing highly significant correlation(P<0.01) and 19 pairs of traits showing a significant correlation(P<0.05). The 21 germplasms in the test could be classified into three major clusters by cluster analysis, with Cluster Ⅱ having the highest number and content of nucleosides, making it suitable for the selection and breeding of P. ternata varieties with high content of nucleosides. The yield in Cluster Ⅲ was higher than that in other groups, making it suitable for the selection and breeding of P. ternata varieties with a high yield. All trait indicators could be simplified into five principal component factors through principal component analysis, and the cumulative contribution rate was up to 86.04%. Further, comprehensive analysis using membership function and stepwise regression analysis identified nine traits, such as plant height, main leaf length, and underground plant height as characteristic indicators for the comprehensive evaluation of germplasm resources of P. ternata. BX007, BX008, and BX005 were identified as germplasms with both high yield and high uridine content, with BX007 having the highest uridine content of 479.51 μg·g~(-1). It belonged to the germplasm of P. ternata with double bulbils and could be cultivated as a potential good variety. Based on the phenotypic classification of P. ternata, systematic resource evaluation was carried out in this study, which could lay a foundation for the excavation of genetic resources and the breeding of new varieties of P. ternata.
Plants, Medicinal ; Pinellia/genetics* ; Plant Breeding ; Phenotype ; Uridine

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines