Background:Tenofovir disoproxil (TDF) is a promising salvage therapy for patients with chronic hepatitis B (CHB) who failed regimens of other nucleoside analogues (NAs). In this study, we aimed to investigate the clinical efficacy and safety of TDF monotherapy in Chinese CHB patients with genotypic resistance.Methods:A total of 33 CHB patients who had failed treatment with other NAs and had genotypic resistance were switched to TDF monotherapy for 48 weeks. Patients’ demographic data (age, sex, history of hepatitis B virus [HBV] therapy), laboratory testing results (hepatitis B e antigen [HBeAg] status, HBV DNA levels, alanine aminotransferase [ALT] levels, serum creatinine, urinary protein, genotypic assay), clinical symptoms, and liver color ultrasound examinations were collected for evaluation at day 0 (baseline) and the 12th, 24th, 36th, and 48th weeks after initiating treatment. Statistical analyses were carried out using rank sum test or rank correlation.Results:With regard to efficacy, the study found that all patients who switched to TDF monotherapy had undetectable HBV DNA levels after 48 weeks. In addition, patients with lower baseline HBV DNA levels realized earlier virological undetectability (rs = 0.39, P = 0.030). ALT levels were normal in 30 of 33 patients (91%). HBeAg negative conversion occurred in 7 of 25 patients (28%), among whom HBeAg seroconversion (12%) and HBeAg seroclearance (16%) occurred. The time of complete virological response was significantly affected by the number of resistance loci (rs = 0.36, P = 0.040). Concerning safety, the study found that no adverse events were observed during the 48 weeks.Conclusion:TDF monotherapy is an effective and safe salvage treatment for CHB patients who are resistant to other NAs.

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Mitofusin‐2 (MFN2) is a transmembrane GTPase that regulates mitochondrial fusion and thereby modulates mitochondrial function. However, the role of MFN2 in lung adenocarcinoma remains controversial. Here, we investigated the effect of MFN2 regulation on mitochondria in lung adenocarcinoma. We found that MFN2 deficiency resulted in decreased UCP4 expression and mitochondrial dysfunction in A549 and H1975 cells. UCP4 overexpression restored ATP and intracellular calcium concentration, but not mtDNA copy number, mitochondrial membrane potential or reactive oxygen species level. Furthermore, mass spectrometry analysis identified 460 overlapping proteins after independent overexpression of MFN2 and UCP4; these proteins were significantly enriched in the cytoskeleton, energy production, and calponin homology (CH) domains. Moreover, the calcium signaling pathway was confirmed to be enriched in KEGG pathway analysis. We also found by protein–protein interaction network analysis that PINK1 may be a key regulator of MFN2‐ and UCP4‐mediated calcium homeostasis. Furthermore, PINK1 increased MFN2/UCP4‐mediated intracellular Ca2+ concentration in A549 and H1975 cells. Finally, we demonstrated that low expression levels of MFN2 and UCP4 in lung adenocarcinoma are associated with poor clinical prognosis. In conclusion, our data suggest not only a potential role of MFN2 and UCP4 in co‐regulating calcium homeostasis in lung adenocarcinoma but also their potential use as therapeutic targets in lung cancer.

Glioma is the most prevalent and aggressive primary nervous system tumor with an unfavorable prognosis. Microtubule plus-end-related genes (MPERGs) play critical biological roles in the cell cycle, cell movement, ciliogenesis, and neuronal development by coordinating microtubule assembly and dynamics. This research seeks to systematically explore the oncological characteristics of these genes in microtubule-enriched glioma, focusing on developing a novel MPERG-based prognostic signature to improve the prognosis and provide more treatment options for glioma patients. First, we thoroughly analyzed and identified 45 differentially expressed MPERGs in glioma. Based on these genes, glioma patients were well distinguished into two subgroups with survival and tumor microenvironment infiltration differences. Next, we further screened the independent prognostic genes (CTTNBP2, KIF18A, NAV1, SLAIN2, SRCIN1, TRIO, and TTBK2) using 36 prognostic-related differentially expressed MPERGs to construct a signature with risk stratification and prognostic prediction ability. An increased risk score was related to the malignant progression of glioma. Therefore, we also designed a nomogram model containing clinical factors to facilitate the clinical use of the risk signature. The prediction accuracy of the signature and nomogram model was verified using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. Finally, we examined the connection between the signature and tumor microenvironment. The signature positively correlated with tumor microenvironment infiltration, especially immunoinhibitors and the tumor mutation load, and negatively correlated with microsatellite instability and cancer stemness. More importantly, immune checkpoint blockade treatment and drug sensitivity analyses confirmed that this prognostic signature was helpful in anticipating the effect of immunotherapy and chemotherapy. In conclusion, this research is the first study to define and validate an MPERG-based signature closely associated with the tumor microenvironment as a reliable and independent prognostic biomarker to guide personalized choices of immunotherapy and chemotherapy for glioma patients.