Optimal early endpoint for second-line or subsequent immune checkpoint inhibitors in previously treated advanced solid cancers: a systematic review.

Background: The administration of second-line or subsequent immune checkpoint inhibitors (ICIs) in previously treated patients with advanced solid cancers has been clinically investigated. However, previous clinical trials lacked an appropriate primary endpoint for efficacy assessment. This systematic review aimed to explore the most optimal early efficacy endpoint for such trials.

Shenqi Qiangjing Granules Ameliorate Asthenozoospermia in Mice by Regulating Ferroptosis through the METTL3/GPX4 Signaling Axis.

Asthenozoospermia is a leading cause of male infertility, yet current pharmacotherapies yield suboptimal outcomes, underscoring the urgent need for novel treatment modalities. Herein, we induced asthenozoospermic mouse models using busulfan and investigated the therapeutic effects of Shenqi Qiangjing Granules (SQ) on testicular pathology, serum sex hormone and steroidogenic enzyme levels, and ferroptosis. Furthermore, utilizing GC-1 spg cell lines, we elucidated the role of the METTL3-mediated mA modification in GPX4 mRNA stability.

Erratum: A Bacterial Pathogen Senses Host Mannose to Coordinate Virulence.

[This corrects the article DOI: 10.1016/j.isci.

Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation.

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses.

Comparing breath hold versus free breathing irradiation for left-sided breast radiotherapy by PlanIQ™.

Background: Breast cancer is the most widespread cancer in women and young women worldwide. Moving towards customised radiotherapy, balancing the use of the available technology with the best treatment modality may not be an easy task in the daily routine. This study aims to evaluate the effectiveness of introducing IQ-feasibility into clinical practice to support the decision of free-breathing (FB) versus breath-hold (BH) left-sided breast irradiations, in order to optimise the technology available and the effectiveness of the treatment.

The QseE-QseF two-component system: A key mediator of epinephrine-regulated virulence in the marine pathogen Edwardsiella piscicida.

Edwardsiella piscicida is a widespread pathogen that infects various fish species and causes massive hemorrhagic septicemia, resulting in significant property damage to the global aquaculture industry. Type III and VI secretion systems (T3/T6SS), controlled by the master regulator EsrB, are important virulence factors of E. piscicida that enable bacterial colonization and evasion from host immune clearance.

Correlation between AI-based CT organ features and normal lung dose in adjuvant radiotherapy following breast-conserving surgery: a multicenter prospective study.

Background: Radiation pneumonitis (RP) is one of the common side effects after adjuvant radiotherapy in breast cancer. Irradiation dose to normal lung was related to RP. We aimed to propose an organ features based on deep learning (DL) model and to evaluate the correlation between normal lung dose and organ features.

Quality Evaluation of Volatile Oil in Yanyangke Mixture (YM) Based on GC-MS Fingerprint, GC Multicomponent Quantitative Analysis and Chemical Pattern Recognition Analysis.

Yanyangke mixture (YM) is composed of 12 kinds of traditional Chinese medicine (TCM) used for the treatment of patients with cough, dry throat and other diseases caused by acute or chronic pharyngitis or patients with difficulty in expectoration. With the wide application of YM in clinical practice, its quality control has attracted huge attention. Based on the multi-component characteristics of Chinese herbal medicines, it is pertinent to establish a quality evaluation system.

Laggera alata Attenuates Inflammatory Response by Regulating Macrophage Polarization in Rheumatoid Arthritis Mice.

Rheumatoid arthritis (RA) is a type of joint injury, which can induce the activation of inflammatory factors and polarization of tissue macrophages. Total phenolics from Laggera alata (TPLA) has been reported to exhibit anti-inflammatory effect in various diseases. However, its specific function in RA is still unknown.

Efficacy and safety of neoadjuvant immunotherapy in resectable esophageal or gastroesophageal junction carcinoma: A pooled analysis of prospective clinical trials.

Neoadjuvant chemoradiotherapy (NCRT) plus radical esophagectomy is currently the standard treatment for resectable esophageal or gastroesophageal junction (GEJ) carcinoma. The aim of this study is to evaluate the efficacy and safety of neoadjuvant immunotherapy in resectable esophageal or GEJ carcinoma. Prospective clinical trials investigating efficacy and/or safety of neoadjuvant immunotherapy with immune checkpoint inhibitors (ICIs) followed by radical esophagectomy in patients with newly diagnosed resectable esophageal or GEJ carcinoma were identified through literature search.

Construction of a novel immune-related prognostic-predicting model of gastric cancer.

Gastric cancer (GC) is a common primary stomach tumor of the central nervous system with a poor prognosis. In this study, 274 differentially expressed immune-related genes (DEIRGs) were identified among six cell subpopulations in GSE112302 single-cell RNA sequencing (scRNA-seq) data of GC. Those DEIRGs were able to divide GC patients into three distinct subtypes with different overall survivals and tumor microenvironment.

A σ-mediated temperature gauge orchestrates type VI secretion system, biofilm formation and cell invasion in pathogen Pseudomonas plecoglossicida.

Pseudomonas plecoglossicida is a temperature-dependent opportunistic pathogen mediating visceral granulomas in many piscine species including the large yellow croaker (Larimichthys crocea) but the underlying mechanisms are unclear. RpoE is an alternative sigma (σ) factor involved in regulated intramembrane proteolytic (RIP) cascade, enabling bacterial pathogens to coordinate the expression of genetic traits associated with stress adaptation and virulence determinants in response to diverse stimuli in vitro and in vivo of the hosts. In this study, genes associated to RIP cascade in P.

Panax notoginseng Saponins Protect Brain Microvascular Endothelial Cells against Oxygen-Glucose Deprivation/Resupply-Induced Necroptosis via Suppression of RIP1-RIP3-MLKL Signaling Pathway.

Recently, necroptosis has emerged as one of the important mechanisms of ischemia stroke. Necroptosis can be rapidly activated in endothelial cells to cause vascular damage and neuroinflammation. Panax notoginseng saponins (PNS), an ingredient extracted from the root of Panax notoginseng (Burk.

Xenogeneic nucleoid-associated EnrR thwarts H-NS silencing of bacterial virulence with unique DNA binding.

Type III and type VI secretion systems (T3/T6SS) are encoded in horizontally acquired genomic islands (GIs) that play crucial roles in evolution and virulence in bacterial pathogens. T3/T6SS expression is subjected to tight control by the host xenogeneic silencer H-NS, but how this mechanism is counteracted remains to be illuminated. Here, we report that xenogeneic nucleoid-associated protein EnrR encoded in a GI is essential for virulence in pathogenic bacteria Edwardsiella and Salmonella.

Retrospective Study on Left-Sided Breast Radiotherapy: Dosimetric Results and Correlation with Physical Factors for Free Breathing and Breath Hold Irradiation Techniques.

In breast radiotherapy, the proximity of the target to sensitive structures together with the uncertainty introduced by respiratory movement, make this treatment one of the most studied to increase its effectiveness. Dosimetric and physical variables play an important role and the study of their correlation and impact on treatment is fundamental. This retrospective study aims to highlight the dosimetric differences of 2 different clinical data sets of patients receiving left-sided breast irradiation in free breathing (FB) or breath hold (BH).

The RIG-I Signal Pathway Mediated Saponin Anti-Inflammatory Effect in Ischemia Stroke.

saponins (PNS), the main bioactive constituents of a traditional Chinese herb , were commonly used for ischemic stroke in China. However, the associated cellular and molecular mechanisms of PNS have not been well examined. This study aimed to decipher the underlying molecular target of PNS in the treatment of cerebral ischemia.

Characterization of a novel live attenuated Edwardsiella piscicida vaccine based on the overexpressed type III secretion system and systematic deletion of the associated effectors.

Edwardsiella piscicida causes edwardsiellosis in a variety of fish species and leads to tremendous economic losses in the global aquaculture industries. Thus, effective and safe prevention and control of this bacterium are urgently needed to combat the related infections. Live attenuated vaccines (LAVs) effectively prevent infectious diseases.

MviN mediates the regulation of environmental osmotic pressure on esrB to control the virulence in the marine fish pathogen Edwardsiella piscicida.

Edwardsiella piscicida is a notorious pathogen infecting diverse kinds of fish and causes substantial economic losses in the global aquaculture industries. The EsrA-EsrB two-component system plays a critical role in the regulation of virulence genes expression, including type III and type VI secretion systems (T3/T6SSs). In this study, the putative regulators of esrB were screened by the transposon insertion sequencing (TIS) technology.

Feasibility of using calibrated cone-beam computed tomography scans to validate the heart dose in left breast post-mastectomy radiotherapy.

Objective: In post-mastectomy radiotherapy, high-conformal techniques are a valid method for determining the dose distribution around a target. However, the proximity of critical structures is a reason for concern. This study aims to evaluate the feasibility of using calibrated cone-beam computed tomography (CBCT) scans as a valid tool for a timely heart dose evaluation.

PepA binds to and negatively regulates esrB to control virulence in the fish pathogen Edwardsiella piscicida.

As an important marine fish pathogen, Edwardsiella piscicida infects a broad range of fish species and causes substantial economic losses. The EsrA-EsrB two-component system is essential for the expression of type III and type VI secretion systems (T3/T6SSs), the key virulence determinants in the bacterium. In this study, a pull-down assay with the esrB promoter as bait was performed to identify the upstream regulators of esrB.

A Bacterial Pathogen Senses Host Mannose to Coordinate Virulence.

Bacterial pathogens are thought to activate expression of virulence genes upon detection of host-associated cues, but identification of the nature of such signals has proved difficult. We generated a genome-scale defined transposon mutant library in Edwardsiella piscicida, an important fish pathogen, to quantify the fitness of insertion mutants for intracellular growth in macrophages and in turbot (Scophthalmus maximus). These screens identified EvrA, a transcription activator that induces expression of esrB, a key virulence regulator.

Evaluation of interfraction setup variations for postmastectomy radiation therapy using EPID-based in vivo dosimetry.

Postmastectomy radiation therapy is technically difficult and can be considered one of the most complex techniques concerning patient setup reproducibility. Slight patient setup variations - particularly when high-conformal treatment techniques are used - can adversely affect the accuracy of the delivered dose and the patient outcome. This research aims to investigate the inter-fraction setup variations occurring in two different scenarios of clinical practice: at the reference and at the current patient setups, when an image-guided system is used or not used, respectively.

Characterization of a prognostic four‑gene methylation signature associated with radiotherapy for head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) remains one of the most common malignancies associated with poor prognosis. DNA methylation has emerged as an important mechanism underlying the radio‑resistance of tumors. Prognostic biomarkers based on radiotherapy‑related aberrant DNA methylation are limited.

Response of Fingernail Growth to Out-of-Field Low-Dose X ray in Cancer Patients Receiving Radiotherapy.

The entire body of a patient with cancer is exposed to low-dose levels of radiation (mGy) during radiation therapy. The safety and biological impact of such exposure to low-dose radiation on the human body are largely unknown. The fingernail is a highly proliferative tissue, and its growth can be monitored during radiation treatment to analyze early effects of low-dose radiation.