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Threaded fasteners are one of the most commonly used connection methods for mechanical structures. Its primary function is to generate appropriate clamping forces and fasten the connected parts. An inappropriate preload can cause loosening, fatigue fracture, and other problems. This will affect the safety and reliability of mechanical equipment. The precise control of the preload has become a critical issue in mechanical assembly processes. Over the past few decades, various tightening measures and methods have been proposed to address this issue. However, many problems continue to exist with practical applications that have not been reviewed comprehensively and systematically. First, various control methods were summarized systematically, and their advantages and disadvantages in engineering applications were analyzed. Torque control is the most widely used tightening method owing to its simple operation and low cost. Therefore, the research on the torque control method was summarized systematically from three aspects: the torque–preload correlation formula, effective friction radius, and friction characteristics during tightening. In addition, the special circumstances that may increase preload uncertainty were discussed. Finally, based on a summary of the current research status, the prospects for future research were discussed. This study would aid researchers in extensively understanding the problems in preload control. [ABSTRACT FROM AUTHOR]

With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0 (AJCC 8th), PS 0–1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors plus chemotherapy (albumin paclitaxel, 260 mg/m2 on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2–4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4 Gy/28F or 50 Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) or S1 (60 mg bid d1–14, 29–42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, among all the patients, 25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 20.4 months (interquartile range [IQR] 8.7–27 months). The median PFS and OS were 17.9 months (95% confidence interval [CI] 11.0–21.9 months) and 20.5 months (95% CI 11.8–27.9 months), respectively. In the subgroup analysis, the median OS was 26.3 months (95% CI 15.33–NA) for patients exhibiting partial response (PR) to CIT, compared to 17 months (95% CI 8.77–26.4) for those with stable disease (SD) or progressive disease (PD), yielding a hazard ratio (HR) of 0.54 (95% CI 0.27–1.06, P = 0.07). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 0.73 (95% CI 0.72–2.6, P = 0.33). The most common Adverse events (AEs) observed during this study were anemia (98.2%), leukopenia (83.9%), thrombocytopenia (53.6%). AEs of grade ≥ 3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula. [ABSTRACT FROM AUTHOR]

Aberrant gene expression caused by miRNAs disorders plays a relevant role in multiple steps of tumorigenesis. In this attempt, we studied the functional role of miR-125b-5p and TPD52 in breast cancer. TPD52 mRNA and miR-125b-5p levels were assessed via qRT-PCR, and TPD52 protein level was analyzed via western blot. By performing CCK-8, transwell invasion and wound healing assays, the phenotype changes in breast cancer cells were assessed. miR-125b-5p was proven as an upstream miRNA of TPD52 in breast cancer via TargetScan database, luciferase activity, and western blot. MiR-125b-5p was prominently decreased while TPD52 was dramatically increased in breast cancer cells. Functional assays exhibited that forced level of TPD52 facilitated cell proliferation, invasion and migration in breast cancer. In the end, the rescue assay proved that miR-125b-5p was a cancer repressor and modulated breast cancer progression by targeting TPD52. All above offer potential biomarkers for breast cancer treatment. [ABSTRACT FROM AUTHOR]

It is well-established that Lysine-specific demethylase 1 (LSD1, also known as KDM1A) roles as a lysine demethylase canonically acting on H3K4me1/2 and H3K9me1/2 for regulating gene expression. Though the discovery of non-histone substrates methylated by LSD1 has largely expanded the functions of LSD1 as a typical demethylase, recent groundbreaking studies unveiled its non-catalytic functions as a second life for this demethylase. We and others found that LSD1 is implicated in the interaction with a line of proteins to exhibit additional non-canonical functions in a demethylase-independent manner. Here, we present an integrated overview of these recent literatures charging LSD1 with unforeseen functions to re-evaluate and summarize its non-catalytic biological roles beyond the current understanding of its demethylase activity. Given LSD1 is reported to be ubiquitously overexpressed in a variety of tumors, it has been generally considered as an innovative target for cancer therapy. We anticipate that these non-canonical functions of LSD1 will arouse the consideration that extending the LSD1-based drug discovery to targeting LSD1 protein interactions non-catalytically, not only its demethylase activity, may be a novel strategy for cancer prevention. [ABSTRACT FROM AUTHOR]