The mechanosensitive ion channel Piezo1 contributes to podocyte cytoskeleton remodeling and development of proteinuria in lupus nephritis.

Piezo1 functions as a special transducer of mechanostress into electrochemical signals and is implicated in the pathogenesis of various diseases across different disciplines. However, whether Piezo1 contributes to the pathogenesis of lupus nephritis (LN) remains elusive. To study this, we applied an agonist and antagonist of Piezo1 to treat lupus-prone MRL/lpr mice. Additionally, a podocyte-specific Piezo1 knockout mouse model was also generated to substantiate the role of Piezo1 in podocyte injury induced by pristane, a murine model of LN. A marked upregulation of Piezo1 was found in podocytes in both human and murine LN. The Piezo1 antagonist, GsMTx4, significantly alleviated glomerulonephritis and tubulointerstitial damage, improved kidney function, decreased proteinuria, and mitigated podocyte foot process effacement in MRL/lpr mice. Moreover, podocyte-specific Piezo1 deletion showed protective effects on the progression of proteinuria and podocyte foot process effacement in the murine LN model. Mechanistically, Piezo1 expression was upregulated by inflammatory cytokines (IL-6, TNF-α and IFN-γ), soluble urokinase Plasminogen Activator Receptor and its own activation. Activation of Piezo1 elicited calcium influx, which subsequently enhanced Rac1 activity and increased active paxillin, thereby promoting cytoskeleton remodeling and decreasing podocyte motility. Thus, our work demonstrated that Piezo1 contributed to podocyte injury and proteinuria progression in LN. Hence, targeted therapy aimed at decreasing or inhibiting Piezo1 could represent a novel strategy to treat LN.

The altered hippocampal functional connectivity and serum brain-derived neurotrophic factor level predict cognitive decline in patients with knee osteoarthritis.

Patients with knee osteoarthritis (KOA) often suffer from cognitive decline and increased dementia risk, but the neurobiological mechanisms remain unclear. In this study, we evaluated cognitive performance and collected brain magnetic resonance imaging (MRI) data and blood samples from cognitively normal KOA patients at baseline sessions and reevaluated their cognition after 5 years. We also collected MRI data from matched healthy controls. Results showed that KOA patients exhibited dysregulated functional connectivities between the hippocampus and thalamus/superior frontal gyrus compared with healthy controls. The altered hippocampal functional connectivities were associated with serum brain-derived neurotrophic factor (BDNF) levels and spatial expression of genes enriched in synaptic plasticity. The hippocampus-thalamus functional connectivity was significantly correlated with patients' memory scores. Moreover, the baseline hippocampus-thalamus functional connectivity and BDNF levels significantly predicted the development of cognitive decline in KOA patients in the follow-up session. Our findings provide insight into the neurobiological underpinnings of KOA and cognitive decline.

Polydatin alleviates bleomycin-induced pulmonary fibrosis and alters the gut microbiota in a mouse model.

To investigate the effect and mechanism of polydatin on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The contents of TNF-α, LPS, IL-6 and IL-1ß in lung tissue, intestine and serum were detected by ELISA. Gut microbiota diversity was detected by 16S rDNA sequencing; R language was used to analyse species composition, α-diversity, ß-diversity, species differences and marker species. Mice were fed drinking water mixed with four antibiotics (ampicillin, neomycin, metronidazole, vancomycin; antibiotics, ABx) to build a mouse model of ABx-induced bacterial depletion; and faecal microbiota from different groups were transplanted into BLM-treated or untreated ABx mice. The histopathological changes and collagen I and α-SMA expression were determined. Polydatin effectively reduced the degree of fibrosis in a BLM-induced pulmonary fibrosis mouse model; BLM and/or polydatin affected the abundance of the dominant gut microbiota in mice. Moreover, faecal microbiota transplantation (FMT) from polydatin-treated BLM mice effectively alleviated lung fibrosis in BLM-treated ABx mice compared with FMT from BLM mice. Polydatin can reduce fibrosis and inflammation in a BLM-induced mouse pulmonary fibrosis model. The alteration of gut microbiota by polydatin may be involved in the therapeutic effect.

The efficacy and safety of telitacicept for the treatment of systemic lupus erythematosus: a real life observational study.

OBJECTIVE: To investigate the efficacy and safety of telitacicept treatment in a Chinese SLE cohort, with real-life settings. METHODS: All patients with SLE who were receiving telitacicept treatment at least 4 weeks were included, and were followed up. Patients received subcutaneous injection of telitacicept weekly based on the standard treatment. SLE responder index-4 (SRI-4) was assessed before the first administration and at least 4 weeks after the first administration. Disease flares during the follow-up period were defined as an increase in disease activity and the number or dose of immunosuppressive drugs. RESULTS: After 4-45 weeks' administration of telitacicept, 80% (n = 16) reached SRI-4 response. The prednisolone dosage declined from a mean of 30.25 mg/d (95% CI 21.99-38.51) before treatment to 13.25 mg/d (95% CI 9.92-16.58) after treatment. The proportion of patients without receiving an immunosuppressive drug increased from 15% to 43% at the endpoint. 19 cases showed various reduction of IgM after treatment (p < 0.05) and C3 and C4 showed either stable or an upward trend. The 24 h urinary protein median value of the 14 cases (baseline 24 h urinary protein >0.5 g/d) showed significant reduction, and 7 of them turned negative. Adverse events were mild to moderate and controllable. CONCLUSION: Telitacicept is a potential treatment option for patients with SLE, especially in lupus nephritis, with significantly increased SRI-4 response rate and reduced the glucocorticoid and immunosuppressive drugs.

Experimental demonstration of real-time optical DFT-S DMT signal transmission for a blue-LED-based UWOC system using spatial diversity reception.

Underwater wireless optical communication (UWOC) has broad prospects in underwater real-time applications. We design and experimentally demonstrate a real-time discrete Fourier transform spread discrete multi-tone (DFT-S DMT) signal transmission based on a field programmable gate array for a blue-LED-based UWOC system with a data rate of up to 30 Mbps over a 15-m underwater channel. The architecture and usage of an on-chip resource as well as power consumption are analyzed and discussed. To reduce the impacts of multipath fading and received intensity fluctuation, spatial diversity reception is also introduced. Furthermore, the receiver sensitivity at a specified bit error rate (BER) threshold and the quality of the images are evaluated using three types of Reed-Solomon (RS) codes. At the BER threshold of 10-4, over 2.8-dB receiver sensitivity improvement is obtained by the DFT-S DMT scheme with the RS (64, 56) code as compared to the uncoded one at the data rate of 30 Mbps. The performance of BER, color difference, and structural similarity in the image transmission of DFT-S DMT is superior to that of the conventional hard clipping quadrature amplitude modulation DMT in a high-data-rate region because of the low peak-to-average-power ratio and ability to mitigate high-frequency fading in a band-limited UWOC system. With schemes of the RS code, DFT-S, and diversity reception, error-free transmission of images is achieved over a 15-m water channel. The proposed UWOC system has the advantages of low power consumption and portability, which foresees a bright future in underwater applications over short to moderate distances.

[Construction of a Risk Prediction Model for Lung Cancer Based on Lifestyle Behaviors in the UK Biobank Large-Scale Population Cohort].

Objective: To identify the risk factors related to lifestyle behaviors that affect the incidence of lung cancer, to build a lung cancer risk prediction model to identify, in the population, individuals who are at high risk, and to facilitate the early detection of lung cancer. Methods: The data used in the study were obtained from the UK Biobank, a database that contains information collected from 502 389 participants between March 2006 and October 2010. Based on domestic and international guidelines for lung cancer screening and high-quality research literature on lung cancer risk factors, high-risk population identification criteria were determined. Univariate Cox regression was performed to screen for risk factors of lung cancer and a multifactor lung cancer risk prediction model was constructed using Cox proportional hazards regression. Based on the comparison of Akaike information criterion and Schoenfeld residual test results, the optimal fitted model assuming proportional hazards was selected. The multiple factor Cox proportional hazards regression was performed to consider the survival time and the population was randomly divided into a training set and a validation set by a ratio of 7:3. The model was built using the training set and the performance of the model was internally validated using the validation set. The area under the receiver operating characteristic (ROC) curve ( AUC) was used to evaluate the efficacy of the model. The population was categorized into low-risk, moderate-risk, and high-risk groups based on the probability of occurrence of 0% to <25%, 25% to <75%, and 75% to 100%. The respective proportions of affected individuals in each risk group were calculated. Results: The study eventually covered 453 558 individuals, and out of the cumulative follow-up of 5 505 402 person-years, a total of 2 330 cases of lung cancer were diagnosed. Cox proportional hazards regression was performed to identify 10 independent variables as predictors of lung cancer, including age, body mass index (BMI), education, income, physical activity, smoking status, alcohol consumption frequency, fresh fruit intake, family history of cancer, and tobacco exposure, and a model was established accordingly. Internal validation results showed that 8 independent variables (all the 10 independent variables screened out except for BMI and fresh fruit intake) were significant influencing factors of lung cancer ( P<0.05). The AUC of the training set for predicting lung cancer occurrence at one year, five years, and ten years were 0.825, 0.785, and 0.777, respectively. The AUC of the validation set for predicting lung cancer occurrence at one year, five years, and ten years were 0.857, 0.782, and 0.765, respectively. 68.38% of the individuals who might develop lung cancer in the future could be identified by screening the high-risk population. Conclusion: We established, in this study, a model for predicting lung cancer risks associated with lifestyle behaviors of a large population. Showing good performance in discriminatory ability, the model can be used as a tool for developing standardized screening strategies for lung cancer.

100-m/3-Gbps underwater wireless optical transmission using a wideband photomultiplier tube (PMT).

In this paper, a wideband photomultiplier tube (PMT)-based underwater wireless optical communication (UWOC) system is proposed and a comprehensive experimental study of the proposed PMT-based UWOC system is conducted, in which the transmission distance, data rate, and attenuation length (AL) is pushed to 100.6 meters, 3 Gbps, and 6.62, respectively. The receiver sensitivity at 100.6-meter underwater transmission is as low as -40 dBm for the 1.5-Gbps on-off keying (OOK) modulation signal. To the best of our knowledge, this is the first Gbps-class UWOC experimental demonstration in >100-meter transmission that has ever been reported. To further minimize the complexity of channel equalization, a sparsity-aware equalizer with orthogonal matching pursuit is adopted to reduce the number of the filter coefficients by more than 50% while keeping slight performance penalty. Furthermore, the performance of the proposed PMT-based UWOC system in different turbidity waters is investigated, which shows the robustness of the proposed scheme. Thanks to the great sensitivity (approaching the quantum limit) and a relatively larger effective area, benefits of misalignment tolerance contributed by the PMT is verified through a proof-of-concept UWOC experiment.

Identification of ferroptosis-related molecular markers in glomeruli and tubulointerstitium of lupus nephritis.

PURPOSE: Ferroptosis, characterized by iron accumulation and lipid peroxidation, is a newly demonstrated form of programed cell death. Present studies reveal that ferroptosis is involved in tumor and neurodegenerative disease. Regarding its roles in the development of LN, it is least interrogated. In this study, we explored whether ferroptosis is activated and how does it change at transcriptomic level in LN. METHODS: 4-Hydroxynonenal (4-HNE) was stained to explore whether ferroptosis is activated. Subsequently, by using bioinformatic methods, public GSE32591 dataset was analyzed. Ferroptosis-related differentially expressed genes (FR-DEGs) were identified in both glomeruli and tubulointerstitium. Immune cell infiltration was evaluated. Correlation between FR-DEGs and infiltrated immune cells was also calculated. Finally, dataset of GSE113342, qPCR, and immunofluorescence staining were also used or performed to validate the results. RESULTS: Expression of 4-HNE was significantly increased in both glomeruli and tubulointerstitium. At transcriptomic level, 19 FR-DEGs in glomeruli and 15 FR-DEGs in tubulointerstitium including genes of iron metabolism, antioxidant system inhibitors, and ferroptosis suppressors were significantly altered in LN. Of which, LTF, CYBB, and CCL5 were upregulated and G0S2 and AKR1C1 were downregulated in both glomeruli and tubulointerstitium of LN. qPCR further validated the alteration of LTF, CYBB, CCL5, G0S2, and AKR1C1 in the whole kidney. Correlation analysis showed that CYBB positively correlated with monocyte infiltration in glomeruli and positively correlated with response to therapy. CONCLUSION: Lipid peroxidation was aberrantly activated in LN, suggesting the activation of ferroptosis. LTF, CYBB, CCL5, G0S2, and AKR1C1, especially CYBB, might be good biomarkers of ferroptosis in LN.

Underwater wireless optical communication utilizing low-complexity sparse pruned-term-based nonlinear decision-feedback equalization.

The nonlinearity of the light-emitting diode (LED) in underwater wireless optical communication (UWOC) systems is considered the one major limiting factor that degrades the system's performance. Volterra series-based nonlinear equalization is widely employed to mitigate such nonlinearity in communication systems. However, the conventional Volterra series-based model is of high complexity, especially for the nonlinearity of higher-order terms or longer memory lengths. In this paper, by pruning away some negligible beating terms and adaptively picking out some of the dominant terms while discarding the trivial ones, we propose and experimentally demonstrate a sparse pruned-term-based nonlinear decision-feedback equalization (SPT-NDFE) scheme for the LED-based UWOC system with an inappreciable performance degradation as compared to systems without the pruning strategy. Meanwhile, by replacing the self/cross beating terms with the terms formed by the absolute operation of a sum of two input samples instead of the product operation terms, a sparse pruned-term-based absolute operation nonlinear decision-feedback equalization (SPT-ANDFE) scheme is also introduced to further reduce complexity. The experimental results show that the SPT-NDFE scheme exhibits comparable performance as compared to the conventional NDFE (nonlinear decision-feedback equalization) scheme with lower complexity (the nonlinear coefficients are reduced by 63.63% as compared to the conventional NDFE scheme). While the SPT-ANDFE scheme yields suboptimal performance with further reduced complexity at the expense of a slight performance degradation, the robustness of the proposed schemes in different turbidity waters is experimentally verified. The proposed channel equalization schemes with low complexity and high performance are promising for power/energy-sensitive UWOC systems.

Acetyl-CoA Carboxylase (ACC) Inhibitor, CP640186, Effectively Inhibited Dengue Virus (DENV) Infection via Regulating ACC Phosphorylation.

Dengue fever is the most common mosquito-borne viral disease and is caused by the dengue virus (DENV). There is still a lack of efficient drugs against DENV infection, so it is urgent to develop new inhibitors for future clinical use. Our previous research indicated the role of VEGFR2/AMPK in regulating cellular metabolism during DENV infection, while acetyl-CoA carboxylase (ACC) is located downstream of AMPK and plays a crucial role in mediating cellular lipid synthesis; therefore, we speculated that an ACC inhibitor could serve as an antiviral agent against DENV. Luckily, we found that CP640186, a reported noncompetitive ACC inhibitor, significantly inhibited DENV proliferation, and CP640186 clearly reduced DENV2 proliferation at an early stage with an EC50 of 0.50 µM. A mechanism study indicated that CP640186 inhibited ACC activation and destroyed the cellular lipid environment for viral proliferation. In the DENV2 infection mice model, oral CP640186 administration (10 mg/kg/day) significantly improved the mice survival rate after DENV2 infection. In summary, our research suggests that lipid synthesis plays an important role during DENV2 proliferation and indicates that CP640186 is a promising drug candidate against DNEV2 in the future.

Experimental demonstration of 50-m/5-Gbps underwater optical wireless communication with low-complexity chaotic encryption.

In this paper, a low-complexity two-level chaotic encryption scheme is introduced and experimentally demonstrated to improve the physical layer security of a 450-nm laser underwater optical wireless communication (UOWC) system using discrete Fourier transform spread discrete multi-tone (DFT-S DMT) modulation. In the first encryption stage, the original bit stream is encrypted with a chaotic sequence based on a one-dimensional Logistic map. In the second encryption stage, the real and imaginary components of the DFT-S symbols are further encrypted with a pair of separate chaotic sequences, which are generated from a two-dimensional Logistic iterative chaotic map with infinite collapse (2D-LICM). The experimental results indicate that the encryption operation has no negative effect on the performance of the proposed UOWC system. For chaotic encryption, the DFT-S DMT gives a better performance than the DMT scheme under different water turbidities. 55-m/4.5-Gbps and 50-m/5-Gbps underwater transmissions are successfully demonstrated by the chaotic encrypted DFT-S DMT scheme. To the best of our knowledge, this is the first time to verify the feasibility of chaotic encryption in a high-speed UOWC system.

The value of the exertional heat stroke score for the prognosis of patients with exertional heat stroke.

OBJECTIVE: This study aims to evaluate the exertional heat stroke score (EHSS) system for the prognosis of exertional heat stroke (EHS) patients. METHODS: Forty-two EHS patients who had been treated in our hospital between January 2017 and December 2019 were divided into two groups according to their prognosis, a survival group and a non-survival group. All the patients had received comprehensive EHS treatment after admission, and their EHSS parameters were collected within 24 h of admission, including body temperature, hepatorenal function, and coagulation function. A retrospective comparative evaluation was made of the effectiveness of the EHSS, the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) in making an EHS prognosis. RESULTS: Among 42 patients, 28 patients were treated successfully and discharged from the hospital, 5 were given a poor prognosis, and 9 died, amounting to a fatality rate of 21.42%. Univariate analysis showed that within 24 h of admission, the differences were statistically significant (p < 0.05) in the comparison of the following factors: lactate concentration, platelets, prothrombin time, fibrinogen, troponin, aspartate aminotransferase, total bilirubin, urinary creatinine, acute gastrointestinal injury, temperature, and Glasgow coma score. However, no statistically significant difference in blood pH was observed between the two groups of patients (p = 0.117). The EHSS, APACHE II, and SOFA scores of the survival group were significantly lower than those of the non-survival group (p < 0.001). The area under the receiver operating characteristic curve of the EHSS, APACHE II and SOFA scores were the area under the curve (AUC) EHSS = 0.96 (0.901, 0.990), AUC Apache II = 0.895 (0.802, 0.950), and AUC SOFA = 0.884 (0.837, 0.964), respectively. Thus, the EHSS diagnostic efficacy of the survival group was significantly higher than that of the other two scores. In addition, the sensitivity and specificity of EHSS were higher than those of the APACHE II and SOFA scores. CONCLUSION: The EHSS has a good diagnostic efficacy for the prognosis of EHS patients and is significantly higher than that of the APACHE II and SOFA scores. This finding provides a theoretical basis for further increasing the rescue success rate of EHS patients and improving their prognostic quality of life.

[Pharmacodynamics and intestinal flora research on different processed products of Puerariae Lobatae Radix and Puerariae Thomsonii Radix].

This study aims to explore the pharmacodynamic differences of Puerariae Lobatae Radix(PLR), Puerariae Thomsonii Radix(PTR) and their different processed products and the influences of these medical materials on the diversity of intestinal flora. The Sennae Folium-induced diarrhea model, streptozotocin(STZ)-induced diabetes model and L-nitro-arginine methyl ester(L-NAME)-induced hypertension model were used to compare the pharmacodynamic differences in anti-diarrhea, blood glucose reduction and blood pressure lowering among raw, roasted and vinegar-processed PLR and PTR. The effects of raw and processed PLR and PTR on intestinal flora diversity of rats were evaluated by 16 S rDNA high-throughput sequencing. The roasted PLR and PTR performed better in anti-diarrhea, especially the former. PLR and its processed products all presented the efficacy of reducing blood glucose, and the vinegar-processed PLR was the most outstanding. The raw PTR was not that effective in reducing blood glucose, whereas its efficacy was improved after roasting and vinegar processing. Both PLR and PTR were capable of lowering blood pressure to a certain extent, and PLR is superior to PTR in this aspect. Further, the vinegar-processed PLR showed the best effect. The diversity of intestinal flora was different among rats to which different products of PLR and PTR were administered. The roasted PLR led to the highest abundance of Lactobacillus, which was closely related to its best antidiarrheal effect. The highest abilities of vinegar-processed PLR to lower blood glucose and blood pressure were associated with the high abundance of Blautia and Prevotella_9. This study lays a foundation for elucidating the processing mechanisms of PLR and PTR and provides a basis for their further development and application.

Emodin suppresses TGF-ß1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway.

Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-ß1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-ß1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-ß1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis.

[Varieties textual research, resource investigation and identification of commercial drugs on Cuscutae Semen].

Through the textual research, resource investigation, literature reviews (including Flora of China, municipal Flora, pharmacopoeia of China and municipal drug standards) and identification of commercial drugs on Cuscutae Semen, it was found the species described in the herbal textual was Cuscuta chinensis, with good quality from Shandong and Henan Province. The identification of commodities showed the majority drugs were from C. australis, varied from the ancient herbal textuals .Mordern literature reviews indicate that it was necessary to strengthen the research on Cuscutae Semen from C. australis, C. chinensis and C. japonica because of their differences in resources, macroscopical and microscopical characters, while wrong descriptions in some literatures. It was suggested that the two species (C. australis and C. chinensis) should be separated in pharmacopoeia of China. The study provides scientific basis for the development and utilization of Cuscutae Semen.

[Effect of Polydatin on Epithelial-Mesenchymal Transition of Human Alveolar Epithelium A549 Cells Induced by TGF-ß1].

OBJECTIVE: To explore the effect of polydatin on the growth of TGF-ß1induced humanalveolar epithelium A549 cells and the mechanism of polydatin for inhibiting the process of epithelial-mesenchymal transition (EMT). METHODS: A549 cells in vitro cultured were randomly divided into five groups, i.e., the blank group, the control group, the low dose polydatin group, the middle dose polydatin group, the high dose polydatin group. Common culture fluid was added in A549 cells of the blank group. Five ng/mLTGF-ß1contained culture fluid was added in A549 cells of the control group. 50, 100, and 150 µmol/mL of polydatin plus 5 ng/mL TGF-ß1contained culture fluid was added in A549 cells of low, middle, and high dosepolydatin groups, respectively. Morphological changes were observed and recorded at different time points. The optimal concentration of polydatin was determined by MTT method. Protein and mRNA expressions of E-cad epithelial cell marker) and Vimentin (mesenchymal cell marker) were detected by Western blot and Real-time PCR. RESULTS: Under inverted phase contrast microscope, A549 cells turned from previous pebble shape to fusiform shape after intervened by polydatin and TGF-ß1. The intercellular space was enlargedand the intercellular connection became loose. These phenomena were more obviously seen in the control group. A549 cells were more satiated in low, middle, and high dose polydatin groups than in the control group. The EMT inhibition was most obviously seen in the middle dose polydatin group at 48 h. Protein and mRNA expressions of E-cad showed an overall descending tendency after intervened by polydatin and TGF-ß1 (P < 0.05). But compared with the control group, protein and mRNA expressions of E-cad were down-regulated in a lesser amplitude in each intervened group. Besides, the tendency was more obviously seen at 48 h than at 24 h. Protein and mRNA expressions of Vimentin showed an overall up-regulating tendency. But compared with the control group, protein and mRNA expressions of Vimentin were down-regulated in a lesser amplitude in each intervened group. Besides, the tendency was more obviously seen at 48 h than at 24 h (P < 0.05). CONCLUSIONS Polydatin could inhibit TGF-ß1 induced EMT process of A549 cells time- and dose-dependently. It also played roles in inhibiting pulmonary fibrosis.

Significance of Trask protein interactions in brain metastatic cohorts of lung cancers.

A class of adhesion protein that occurs in the membrane with both extracellular and intracellular domain and play vital role in maintaining multicellularity is TRASK, also called CUB-domain containing protein1, CD318 (CDCP1). Specifically, in the current study, documented aggressive grades of lung cancers and distant metastatic tissues were examined for protein interactions of Trask and compared with lung cancer variants in situ. The intracellular domain of Trask has the ability to undergo tyrosine phosphorylation and thereafter undergo increased genomic expression, as well as interact with cytoskeletal proteins in the cell periphery and other local signal transduction machinery to induce invadopodia formation and distant metastasis. We incorporated proximity ligation assay to examine protein interactions of Trask in metastatic lung cancer tissues and compare with advanced and low-grade lung cancers restricted to the primary site of origins. Here, we provide direct evidence that activated Trask, which is a phosphorylated form, binds with cytoskeletal proteins actin and spectrin. These interactions were not seen in locally growing lung cancer and cancer in situ. These interactions may be responsible for invadopodia formation and breaking free from a multicellular environment. Functional studies demonstrated interaction between Trask and the STOCs Orai1 and Stim1. Calcium release from internal stores was highest in metastatic lung cancers, suggesting this mechanism as an initial stimulus for the cells to respond chaotically to external growth factor stimulation, especially in aggressive metastatic variants of lung cancers. Recently, inhibitors of STOCs have been identified, and preclinical evidence may be obtained whether these drugs may be of benefit in preventing the deadly consequences of lung cancer.

Low thyroid function is associated with metabolic dysfunction-associated steatotic liver disease.

Background and Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is recently introduced to better highlight the pathogenic significance of cardiometabolic dysfunction, as compared with non-alcoholic fatty liver disease. This study aimed to investigate the association between low thyroid function and MASLD in the new context. Methods: We recruited 2901 participants for our retrospective cohort study from 2016 to 2021. Participants were divided into strict-normal thyroid function and low thyroid function groups (low-normal thyroid function, subclinical hypothyroidism) based on initial thyroid stimulating hormone (TSH) levels, respectively. Cox regression models were used to estimate the hazard ratios (HRs) and 95% CI. Results: During a median follow-up of 15.6 months, 165 (8.9%) strict-normal thyroid function subjects and 141 (13.4%) low thyroid function subjects developed MASLD; this result was statistically relevant (P < 0.05). Univariate regression analysis showed that low thyroid function and subclinical hypothyroidism were statistically significantly associated with MASLD (low thyroid function: HR1.53; 95% CI 1.22-1.92; subclinical hypothyroidism: HR1.95; 95% CI 1.47-2.60). Conclusions: MASLD is associated with low thyroid function and the relationship between MASLD and low thyroid function is independent.

Plant medicine metabolite Yulinzhu treating neurological disorder causing polycystic ovary syndrome: a systematic review and a meta-analysis.

Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder that affects women of reproductive age, characterized by chronic anovulation, hyperandrogenism, and polycystic ovarian morphology. Emerging evidence indicates that neurological disorders play a significant role in the etiology of PCOS, highlighting the complex interplay between the central nervous system (CNS) and ovarian function. Yulinzhu, a traditional Chinese medicine (TCM) formulation, has been traditionally used to regulate menstrual cycles and improve fertility. This study aims to investigate the efficacy and mechanisms of Yulinzhu in treating PCOS induced by neurological disorders. Methods: An extensive literature search was performed across electronic databases such as PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI), covering publications up to 1 June 2024. The review included randomized controlled trials (RCTs) that compared Yulin Zhu with placebo, standard care, or other active treatments in patients with PCOS. Two reviewers independently carried out data extraction and quality assessment. Meta-analyses were conducted using both fixed and random-effects models, with heterogeneity evaluated using the I2 statistic. Results: We screened 891 records and included 6 studi es in the meta-analysis. The meta-analysis revealed that Yulinzhu about effective rate [RR = 1.19, 95% CI (1.10, 1.29), p < 0.0001], pregnancy rate [RR = 2.80, 95% CI (1.65, 4.76), p < 0.0001] and ovulation rate [RR = 1.33, 95% CI (1.10, 1.62), p = 0.04]. Meta-analysis shows the results of follicle estrogen [WMD = 0.69, 95% CI (-0.39, 1.78), p = 0.21], luteinizing hormone [WMD = -2.27, 95% CI (-3.86, -0.67), p = 0.005], testosterone [WMD = -0.44, 95% CI (-0.64, -0.25), p < 0.0001], estradiol [WMD = 16.20, 95% CI (2.74, 29.67), p < 0.0001]. Conclusion: This study demonstrates that plant medicine compund Yulinzhu may effectively treats PCOS including hormonal regulation, anti-inflammatory actions, and neuroprotection. We expect further research with larger, well-designed clinical trials to substantiate our conclusions.

The volumes of amygdala subregions and peripheral programmed cell death protein-1 levels are associated with cognitive decline in individuals with knee osteoarthritis.

BACKGROUND: Persistent pain is a prominent symptom of knee osteoarthritis (KOA) and has been associated with cognitive decline in individuals with KOA. The amygdala, a complex structure consisting of nine subnuclei, and programmed cell death protein-1 (PD-1) levels play crucial roles in pain regulation and cognitive processing. This study aims to investigate the relationships among amygdala subregion volumes, cognitive function, and PD-1 levels to elucidate the underlying mechanism of cognitive decline in KOA. METHODS: In this cross-sectional study, we recruited 36 patients with KOA and 25 age/gender-matched healthy controls for neuropsychological tests, structural magnetic resonance imaging scanning, and measurement of serum PD-1 levels. We used the atlas provided by FreeSurfer software to automatically segment the amygdala subnuclei. Subsequently, we compared the volumes of amygdala subregions between groups and explored their correlation with clinical scores and PD-1 levels. RESULTS: Compared to healthy controls, individuals with KOA exhibited significantly lower scores on global cognition tasks, such as long-delay free recall, short-delay free recall, and immediate recall tasks. Moreover, they displayed decreased volumes in lateral nucleus basal nucleus paralaminar nucleus while showing increased volumes in accessory basal nucleus, central nucleus, medial nucleus, and cortical nucleus. Within the KOA group specifically, paralaminar volume was negatively correlated with immediate recall scores; pain scores were negatively correlated with global cognition; basal volume was negatively correlated with PD-1 levels. CONCLUSION: Our findings highlight those alterations in amygdala subregion volumes along with changes in serum PD-1 levels may contribute to observe cognitive decline among individuals suffering from KOA.