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 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.

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.

Updated incidence rates and risk factors of esophageal cancer in Nan'ao Island, a coastal high-risk area in southern China.

Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.

Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis.

Advances in lung cancer research applying machine learning (ML) technology have generated many relevant literature. However, there is absence of bibliometric analysis review that aids a comprehensive understanding of this field and its progress. Present article for the first time performed a bibliometric analysis to clarify research status and focus from 2010 to 2021. In the analysis, a total of 2,312 relevant literature were searched and retrieved from the Web of Science Core Collection database. We conducted a bibliometric analysis and further visualization. During that time, exponentially growing annual publication and our model have shown a flourishing research prospect. Annual citation reached the peak in 2017. Researchers from United States and China have produced most of the relevant literature and strongest partnership between them. Medical image analysis and Nature appeared to bring more attention to the public. The computer-aided diagnosis, precision medicine, and survival prediction were the focus of research, reflecting the development trend at that period. ML did make a big difference in lung cancer research in the past decade.

cGAS-STING pathway in ischemia-reperfusion injury: a potential target to improve transplantation outcomes.

Transplantation is an important life-saving therapeutic choice for patients with organ or tissue failure once all other treatment options are exhausted. However, most allografts become damaged over an extended period, and post-transplantation survival is limited. Ischemia reperfusion injury (IRI) tends to be associated with a poor prognosis; resultant severe primary graft dysfunction is the main cause of transplant failure. Targeting the cGAS-STING pathway has recently been shown to be an effective approach for improving transplantation outcomes, when activated or inhibited cGAS-STING pathway, IRI can be alleviated by regulating inflammatory response and programmed cell death. Thus, continuing efforts to develop selective agonists and antagonists may bring great hopes to post-transplant patient. In this mini-review, we reviewed the role of the cGAS-STING pathway in transplantation, and summarized the crosstalk between this pathway and inflammatory response and programmed cell death during IRI, aiming to provide novel insights into the development of therapies to improve patient outcome after transplantation.

Selective depolymerization of lignosulfonate via hydrogen transfer enhanced in an emulsion microreactor.

An efficient emulsion microreactor was constructed for selective conversion of lignosulfonate via hydrogen transfer reaction based on the self-surfactivity of this natural aromatic polymer. Industrial Raney Ni and isopropanol were used as catalyst and hydrogen donor, respectively. The results showed that the emulsion microreactor has a remarkable process intensification effect on the lignosulfonate depolymerization. Under mild condition of 473 K for 2.0 h, 116.1 mg g-1 of volatile phenolic monomer can be obtained, which is twice of that from other investigated processes without emulsion of this work. In particular, 39.3 mg g-1 of which is composed of 4-ethyl guaiacol, an important and versatile chemical currently from petrochemical industry. Furthermore, the solvent separates to two phases automatically after reaction due to the consumption of lignosulfonate, which makes handy products enrichment and separation. Additionally, the emulsion microreactor is significantly affected by hydrogen donor and is efficient for other lignin sources as well.

Halorubrum litoreum sp. nov., an extremely halophilic archaeon from a solar saltern.

An extremely halophilic archaeon, strain Fa-1(T), was isolated from a marine solar saltern in Fujian, China. Strain Fa-1(T) required Mg2+ and at least 2.0 M NaCl for growth. It was able to grow at pH 6.5-9.0 (optimally at pH 7.0-7.5) and at 20-55 degrees C (optimally at 37-42 degrees C). The major polar lipids of strain Fa-1(T) were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and a sulfated diglycosyl diether. On the basis of a 16S rRNA gene sequence analysis, strain Fa-1(T) was closely related to nine species of the genus Halorubrum, showing sequence similarities of 97.4-98.4 %. The G+C content of the DNA of strain Fa-1(T) is 64.9 mol% (Tm). DNA-DNA hybridization values between strain Fa-1(T) and the most closely related members of the genus Halorubrum were below 51 %. On the basis of the data from this study, strain Fa-1(T) represents a novel species of the genus Halorubrum, for which the name Halorubrum litoreum sp. nov. is proposed. The type strain is Fa-1(T) (=CGMCC 1.5336(T) =JCM 13561(T)).