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Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumors in the Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality, and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples from July 2021 to August 2022. Among the cohort, 2337 (82%) cases possess genetic alterations, including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%), and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF-positive papillary thyroid cancer (PTC) patients tend to have older age, smaller tumor size, less vascular invasion, more frequent tumor multifocality, and a significantly higher cervical lymph node metastatic rate. Mutation at RET gene codons 918 and 634 is strongly correlated with medullary thyroid cancer. However, it did not display more invasive clinical characteristics. TERT-positive patients are more likely to have older age, and have larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating a poor prognosis. Patients with TERT, RET/PTC1, and CHEK2 mutations are more susceptible to lateral lymph node metastasis. In conclusion, NGS can be a useful tool that provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.

[Objective] In order to actively and steadily promote the dual carbon goals and effectively solve the problem of carbon inequity in various provinces, it is important to build a complete, reasonable, and easy-to-implement provincial carbon compensation mechanism. [Methods] Based on the IPCC inventory method, the inter-regional bilateral carbon transfer calculation model, and the row arrange series (RAS) method, this study incorporated the relationship between carbon sources and carbon sinks within the region (reflecting the differences between natural and production factors) and the carbon transfer of cross-regional trade (reflecting the differences between economic and consumption factors) into a unified carbon compensation framework, introduced the “revenue and expenditure-responsibility and benefit” dual balance perspective, constructed a inter-provincial carbon compensation framework of compensation basis, compensation subject, compensation standard, and compensation method, and explored the pathways of provincial carbon compensation that effectively integrate with the dual carbon goals and their carbon reduction mechanisms. [Results] The results show that: (1) Compared with the previous perspectives (“revenue and expenditure” perspective and “responsibility and benefit” perspective), the provinces that bear more embodied carbon emissions from trade, being carbon sinks, and have less carbon emissions within the region, receive more compensation using the “revenue and expenditure-responsibility and benefit” dual balance perspective. (2) Quota compensation schemes based on comprehensive principles are more suitable for inclusion in the fairness-oriented carbon compensation mechanism than those that prioritize fairness or efficiency separately. (3) During the “historical compensation period” (2012-2021), Guangdong, Zhejiang, Beijing, and Chongqing were the four provinces with the largest compensation amounts, and Inner Mongolia, Hebei, Xinjiang, Heilongjiang, and Shanxi were the five provinces with the largest compensated amounts. (4) During the “future compensation period” (2022-2030), Inner Mongolia, Hebei, and Shanxi with greater carbon emission reduction potential will have carbon quota deficits, and Guangdong, Fujian, Tianjin, and Shanghai with high economic benefits per unit of carbon emissions will have carbon quota surpluses. [Conclusion] The carbon compensation mechanism proposed in this paper based on the dual balance perspective of “revenue and expenditure responsibility benefit” is more fair and operable, and can serve as an important reference for the policy design of China’s provincial carbon compensation mechanism. The comprehensive supporting system of the carbon compensation mechanism can be improved and pilot work can be carried out.

Two numerical schemes are proposed and investigated for the Yang–Mills equations, which can be seen as a nonlinear generalisation of the Maxwell equations set on Lie algebra-valued functions, with similarities to certain formulations of General Relativity. Both schemes are built on the Discrete de Rham (DDR) method, and inherit from its main features: an arbitrary order of accuracy, and applicability to generic polyhedral meshes. They make use of the complex property of the DDR, together with a Lagrange-multiplier approach, to preserve, at the discrete level, a nonlinear constraint associated with the Yang–Mills equations. We also show that the schemes satisfy a discrete energy dissipation (the dissipation coming solely from the implicit time stepping). Issues around the practical implementations of the schemes are discussed; in particular, the assembly of the local contributions in a way that minimises the price we pay in dealing with nonlinear terms, in conjunction with the tensorisation coming from the Lie algebra. Numerical tests are provided using a manufactured solution, and show that both schemes display a convergence in $ L^2 $-norm of the potential and electrical fields in $ \mathcal O(h^{k+1}) $ (provided that the time step is of that order), where $ k $ is the polynomial degree chosen for the DDR complex. We also numerically demonstrate the preservation of the constraint.

Abstract Background Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear. Methods The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment. The effect of hippocampal hyperglycemia on microglial activation was evaluated through hippocampal glucose-infusion and the incubation of BV2 cells with high glucose. The gain-and loss-of-function experiments were conducted to investigate the role of GLUT1 in microglial proinflammatory activation. An adeno-associated virus (AAV) was employed to specifically knockdown of GLUT1 in hippocampal microglia to assess its impact on stressed-mice. Results Herein, we found that chronic stress induced remarkable hippocampal microglial proinflammatory activation and neuroinflammation, which were involved in the development of stress-related spatial learning and memory impairment. Mechanistically, elevated hippocampal glucose level post-stress was revealed to be a key regulator of proinflammatory microglial activation via specifically increasing the expression of microglial GLUT1. GLUT1 overexpression promoted microglial proinflammatory phenotype while inhibiting GLUT1 function mitigated this effect under high glucose. Furthermore, specific downregulation of hippocampal microglial GLUT1 in stressed-mice relieved microglial proinflammatory activation, neuroinflammation, and spatial learning and memory injury. Finally, the NF-κB signaling pathway was demonstrated to be involved in the regulatory effect of GLUT1 on microglia. Conclusions We demonstrate that elevated glucose and GLUT1 expression induce microglia proinflammatory activation, contributing to stress-associated spatial memory dysfunction. These findings highlight significant interplay between metabolism and inflammation, presenting a possible therapeutic target for stress-related cognitive disorders.

Abstract KIFC3 is a member of Kinesin-14 family motor proteins, which play a variety of roles such as centrosome cohesion, cytokinesis, vesicles transportation and cell proliferation in mitosis. Here, we investigated the functional roles of KIFC3 in meiosis. Our findings demonstrated that KIFC3 exhibited expression and localization at centromeres during metaphase I, followed by translocation to the midbody at telophase I throughout mouse oocyte meiosis. Disruption of KIFC3 activity resulted in defective polar body extrusion. We observed aberrant meiotic spindles and misaligned chromosomes, accompanied by the loss of kinetochore-microtubule attachment, which might be due to the failed recruitment of BubR1/Bub3. Coimmunoprecipitation data revealed that KIFC3 plays a crucial role in maintaining the acetylated tubulin level mediated by Sirt2, thereby influencing microtubule stability. Additionally, our findings demonstrated an interaction between KIFC3 and PRC1 in regulating midbody formation during telophase I, which is involved in cytokinesis regulation. Collectively, these results underscore the essential contribution of KIFC3 to spindle assembly and cytokinesis during mouse oocyte meiosis.

Background We compared the diagnostic performance of the short five-item and full seven-item Mini Sarcopenia Risk Assessment Questionnaire (MSRA-5 and MSRA-7) against the Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F) and SARC-F with calf circumference (SARC-CalF) scales for sarcopenia in healthy community-dwelling older adults. Methods We conducted a post-hoc cross-sectional secondary data analysis of a prospective cohort study, using data from 230 older adults (mean age 67.2±7.4 years, 92% Chinese, and 73% female) from the “Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and Osteosarcopenic Obesity in predicting frailty and functional decline in community-dwelling Asian older adults Study” (GeriLABS-2) conducted between December 2017 and March 2019 in Singapore. We performed receiver operating characteristic curve analysis to ascertain the area under the curve (AUC) for sarcopenia diagnosis using the Asian Working Group for Sarcopenia 2019 consensus criteria. We applied the DeLong method to compare the AUCs of the four instruments. Results The MSRA-5 and MSRA-7 demonstrated poor diagnostic performance (AUC of 0.511, 95% confidence interval [CI] 0.433–0.589 and AUC of 0.526, 95% CI 0.445–0.606, respectively), compared to that in SARC-CalF (AUC of 0.739, 95% CI 0.671–0.808) and SARC-F (AUC of 0.564, 95% CI 0.591–0.636). The SARC-CalF demonstrated significantly superior discriminatory ability compared to that in the SARC-F, MSRA-5, and MSRA-7 (all p

A traditional Chinese herbal medicine formula named Huang-Lian-Jie-Du Decoction (HLJDD) has been used to cure various inflammatory diseases with a long history. However, one component of HLJDD Gardeniae fructus has remarkable liver and kidney toxicities. Therefore, it was altered with Dictamni cortex to form a modified HLJDD (MHLJDD). In this study, we aimed to evaluate the sub-chronic toxicity of the active fraction of MHLJDD (MHLJDD-F) in rats. Adult rats of both sexes were intragastrically administered with vehicle or MHLJDD-F (at the dose of 170, 340, and 680 mg/kg/day) once daily for 90 days. Half of the rats from each group were kept for an additional 30-day period to observe the drug withdrawal effect. The signs of toxicity and mortality of the rats were observed, and the body weight and food consumption were recorded. Blood was collected for hematological and biochemical analyses and major organs were weighed and harvested for histopathological examinations. The results revealed that no systemic toxicity of MHLJDD-F was found during the experiments. Organ coefficients and pathological alterations of major organs were comparable to the control rats. The no-observed adverse effect level (NOAEL) of MHLJDD-F was found up to 680 mg/kg/day. All these results demonstrated that long-term oral administration of MHLJDD-F did not cause significant toxicity, which is worthy to be widely applied as a new herbal medicine in pre-clinical and clinical studies.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon compound that is generated during combustion processes, and is present in various substances such as foods, tobacco smoke, and burning emissions. BaP is extensively acknowledged as a highly carcinogenic substance to induce multiple forms of cancer, such as lung cancer, skin cancer, and stomach cancer. Recently it is shown to adversely affect the reproductive system. Nevertheless, the potential toxicity of BaP on oocyte quality remains unclear. In this study, we established a BaP exposure model via mouse oral gavage and found that BaP exposure resulted in a notable decrease in the ovarian weight, number of GV oocytes in ovarian, and oocyte maturation competence. BaP exposure caused ribosomal dysfunction, characterized by a decrease in the expression of RPS3 and HPG in oocytes. BaP exposure also caused abnormal distribution of the endoplasmic reticulum (ER) and induced ER stress, as indicated by increased expression of GRP78. Besides, the Golgi apparatus exhibited an abnormal localization pattern, which was confirmed by the GM130 localization. Disruption of vesicle transport processes was observed by the abnormal expression and localization of Rab10. Additionally, an enhanced lysosome and LC3 fluorescence intensity indicated the occurrence of protein degradation in oocytes. In summary, our results suggested that BaP exposure disrupted the distribution and functioning of organelles, consequently affecting the developmental competence of mouse oocytes.

Summary: Circadian rhythms are internal biological rhythms driving temporal tissue-specific, metabolic programs. Loss of the circadian transcription factor BMAL1 in the paraventricular nucleus (PVN) of the hypothalamus reveals its importance in metabolic rhythms, but its functions in individual PVN cells are poorly understood. Here, loss of BMAL1 in the PVN results in arrhythmicity of processes controlling energy balance and alters peripheral diurnal gene expression. BMAL1 chromatin immunoprecipitation sequencing (ChIP-seq) and single-nucleus RNA sequencing (snRNA-seq) reveal its temporal regulation of target genes, including oxytocin (OXT), and restoring circulating OXT peaks in BMAL1-PVN knockout (KO) mice rescues absent activity rhythms. While glutamatergic neurons undergo day/night changes in expression of genes involved in cell morphogenesis, astrocytes and oligodendrocytes show gene expression changes in cytoskeletal organization and oxidative phosphorylation. Collectively, our findings show diurnal gene regulation in neuronal and non-neuronal PVN cells and that BMAL1 contributes to diurnal OXT secretion, which is important for systemic diurnal rhythms.

Objective The maximum operating pressure for underground gas storage facilities designed for oil and gas reservoirs, both constructed and under construction in China, is currently set at the original formation pressure. There have yet to be successful cases of overpressure operation, which significantly impacts the economic benefits of converting depleted oil and gas reservoirs into underground gas storage facilities. This article aims to evaluate the maximum operating pressure and storage capacity of the Nanpu 1-29 gas storage facility from the perspective of the ultimate bearing capacity of cap layers and faults, with the goal of effectively enhancing the construction benefits of the facility. Methods The evaluation of the maximum operating pressure for the Nanpu 1-29 gas storage facility in eastern Hebei is based on the minimum principal stress measured in situ in the mining wells. Different effective porosity calculation methods are employed to quantitatively evaluate the effective storage capacity of gas and oil reservoirs, as well as the incremental capacity after pressure boosting operation, based on their development differences. Results The evaluation of the maximum operating pressure for the Nanpu 1-29 gas storage facility indicates that the minimum principal stress of the cap layers determined by the in-situ measurements in the mining wells is 34.00 MPa. Based on the tensile failure criteria determined by the minimum principal stress, the maximum operating pressure for the tensile failure of the cap layer is 27.20 MPa. Combined with the maximum safe injection pressure corresponding to shear failure of the cap layer (30.60 MPa) and the maximum safe injection pressure corresponding to unstable slip of the fault (27.60 MPa), the final maximum operating pressure for the Nanpu 1-29 gas storage facility is determined to be 27.20 MPa. Based on the effective storage capacity calculation model, considering factors such as the water content of the gas reservoir, residual water and edge porosity as well as the coefficient of influence, the efficiency of gas-driven fluid, and the utilization rate of oil-containing space, the maximum operating pressure increased from the original formation pressure of 22.50 MPa to 27.20 MPa. The practical storage capacity of the gas storage facility increased from 15.46×108 m3 to 18.14×108 m3, an increase of approximately 17.3%. Conclusion (1) The construction of gas storage facilities can be re-evaluated for the maximum operating pressure based on the minimum principal stress measured in situ in the mining wells, and overpressure design can be conducted under appropriate conditions. (2) Overpressure design can effectively increase storage capacity and improve the economic benefits of reservoir construction. Significance The research results have a certain reference value for the quantitative evaluation of the maximum operating pressure and storage capacity of other underground gas storage facilities, and are expected to significantly improve the economic benefits of overpressure-designed reservoir-type gas storage facilities in China.

Abstract Background Qing-Zao-Jiu-Fei Decoction (QZJFD) is a famous herbal formula commonly prescribed for the treatment of lung-related diseases in the ancient and modern times. Trichosanthis Fructus (TF) and Fritillariae Thunbergii Bulbus (FTB) are widely used for treatment of cough and pulmonary disease. In order to identify a more effective formula for treatment of pulmonary fibrosis, we intend to add TF and FTB in QZJFD to form a modified QZJFD (MQZJFD). In this study, we aims to explore MQZJFD as an innovative therapeutic agent for pulmonary fibrosis using bleomycin (BLM)-treated rats and to unravel the underlying molecular mechanisms. Methods BLM was given to SD rats by intra-tracheal administration of a single dose of BLM (5 mg/kg). QZJFD (3 g/kg) and MQZJFD (1, 2 and 4 g/kg) was given intragastrically daily to rats for 14 days (from day 15 to 28) after BLM administration for 14 consecutive days. Results MQZJFD was found to contain 0.29% of amygdalin, 0.020% of lutin, 0.077% of glycyrrhizic acid and 0.047% of chlorogenic acid. BLM treatment could induce collagen deposition in the lung tissues of rats, indicating that the pulmonary fibrosis rat model had been successfully established. MQZJFD have better effects than the original QZJFD in reducing the pulmonary structure damage and collagen deposition of rat lung fibrosis induced by BLM. MQZJFD could reduce the hydroxyproline content in lung tissues of BLM-treated rats. The biomarkers of fibrosis such as matrix metalloproteinase 9 (MMP9), collagen I and α-smooth muscle actin (α-SMA) were remarkably reduced after treatment with MQZJFD. MQZJFD also have anti-oxidant stress effects by inhibiting the level of malondialdehyde (MDA), but enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the level of glutathione (GSH) in the lung tissues of BLM-treated rats. Moreover, the MQZJFD markedly suppressed the over expressions of p-p65/p65 and p-IκBα/IκBα, but upregulated the Nrf2. MQZJFD also suppressed the protein expressions of p-ERK1/2/ERK1/2, p-p38/p38 and p-JNK/JNK in the lung tissues of BLM-treated rats. Conclusions MQZJFD could improve the pulmonary fibrosis induced by BLM in rats via inhibiting the fibrosis and oxidative stress via suppressing the activation of NF-κB/Nrf2 and MAPKs pathways.

Abstract According to statistics, the incidence of liver cancer is increasing yearly, and effective treatment of liver cancer is imminent. For early liver cancer, resection surgery is currently the most effective treatment. However, resection does not treat the disease in advanced patients, so finding a method with a better prognosis is necessary. In recent years, ferroptosis and cuproptosis have been gradually defined, and related studies have proved that they show excellent results in the therapy of liver cancer. Cuproptosis is a new form of cell death, and the use of cuproptosis combined with ferroptosis to inhibit the production of hepatocellular carcinoma cells has good development prospects and is worthy of in-depth discussion by researchers. In this review, we summarize the research progress on cuproptosis combined with ferroptosis in treating liver cancer, analyze the value of cuproptosis and ferroptosis in the immune of liver cancer, and propose potential pathways in oncotherapy with the combination of cuproptosis and ferroptosis, which can provide background knowledge for subsequent related research.

Background Frailty is prevalent in acute care and is associated with negative outcomes. While a comprehensive geriatric assessment to identify geriatric syndromes is recommended after identifying frailty, more evidence is needed to support this approach in the inpatient setting. This study examined the association between frailty and geriatric syndromes and their impact on outcomes in acutely admitted older adults. Methods A total of 733 individuals aged ≥65 years admitted to the General Surgery Service of a tertiary hospital were assessed for frailty using the Clinical Frailty Scale (CFS) and for geriatric syndromes using routine nursing admission assessments, including cognitive impairment, falls, incontinence, malnutrition, and poor oral health. Multinomial logistic regression and Cox regression were used to evaluate the associations between frailty and geriatric syndromes and their concomitant impact on hospital length of stay (LOS) and 30-day readmissions. Results Greater frailty severity was associated with an increased likelihood of geriatric syndromes. Individuals categorized as CFS 4–6 and CFS 7–8 with concomitant geriatric syndromes had 29% and 35% increased risks of a longer LOS, respectively. CFS 4–6 was significantly associated with functional decline (relative risk ratio =1.46; 95% confidence interval [CI], 1.03–2.07) and 30-day readmission (hazare ratio=1.78; 95% CI, 1.04–3.04), whereas these associations were not significant for CFS 7–8. Conclusions Geriatric syndromes in frail individuals can be identified from routine nursing assessments and represent a potential approach for targeted interventions following frailty identification. Tailored interventions may be necessary to achieve optimal outcomes at different stages of frailty. Further research is required to evaluate interventions for older adults with frailty in a wider hospital context.

AIM: To describe the outcome of using low-dose laser cycloplasty (LCP) in chronic angle-closure glaucoma (CACG). METHODS: A retrospective case series. Medical charts of CACG patients who underwent LCP in the Eye Hospital of Wenzhou Medical University were reviewed. The main outcomes included intraocular pressure (IOP), the number of glaucoma medication, anterior segment parameters and surgery-related complications. RESULTS: A total of 7 eyes of 7 CACG patients (age 38.9±11.0y) underwent LCP with a mean follow-up of 27.1±13.7mo (range 16–48mo). Following LCP, mean IOP and glaucoma medications decreased from 26.1±6.1 mm Hg with 3.1±1.1 glaucoma medications pre-treatment to 14.9±3.1 mm Hg (P=0.027) with 0.4±1.1 glaucoma medications (P=0.001) at final follow-up. The anterior chamber depth (ACD), angle opening distance500 and trabecular-iris angle increased from 1.65±0.33 mm, 0.05 mm (range 0–0.30 mm) and 5.1° (range, 0–31.97°) at baseline to 1.98±0.43 mm (P=0.073), 0.53 mm (range 0.42–0.91 mm, P=0.015), 45.9° (range, 40.2°–59.4°, (P=0.015) in the long-term follow-up, respectively. The deepening of ACD and reopening of anterior chamber angle (ACA) was observed in 6 eyes (85.7%). CONCLUSION: LCP is a promising treatment option for patients with CACG via reducing IOP and glaucoma medication without serious complications. In addition, LCP can bring a significant deepening in ACD and reopening of ACA.

Globally, alcohol consumption is responsible for an estimated 3 million deaths annually and contributes to over 740,000 new cancer cases each year.1 Acetaldehyde, a byproduct of alcohol metabolism, has been designated as first-class carcinogens by the International Agency for Research on Cancer.2 In East Asian countries such as China, Japan and Korea, approximately 36% of the population cannot effectively metabolise alcohol due to an inherited deficiency in the enzyme aldehyde dehydrogenase 2 (ALDH2).3 This deficiency leads to the accumulation of acetaldehyde in the blood, causing alcohol flushing syndrome (AFS), characterised by facial flushing, palpitations and nausea.4 AFS is a predictor of inactive ALDH2 and is associated with a higher risk of cancer development.