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Abstract Objective The purpose of this study is to assess the impact of physical activity on both therapeutic efficacy and immune-related adverse events (irAEs) during immunotherapy for non-small cell lung cancer (NSCLC). Methods Physical activity was divided into three groups: light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) for laboratory indexes, efficacy, and irAEs. A multivariate logistic regression was employed to analyze the relationship between sedentary behavior with efficacy and irAEs. Results The study included 121 patients. The three levels of physical activity were not significantly associated with efficacy or irAEs. However, noteworthy disparities were observed in base-hemoglobin levels (F = 3.4, P = 0.037) and base-lymphocyte levels (χ2 = 6.13, P = 0.047) among the three groups. After treatment, we identified statistically significant variations in albumin levels (P = 0.012) and lymphocyte counts (P = 0.035). Furthermore, a negative correlation emerged between pre-treatment sedentary behavior duration and immune-efficacy (β: −0.005, P = 0.027). Conclusions In summary, within the cohort of NSCLC patients undergoing single immunotherapy or a combination of immunotherapy and chemotherapy, physical activity is closely related to immune and inflammatory indicators in patients, and prolonged sitting will reduce the therapeutic effect.

Abstract Dysregulated gene expression and imbalance of transcriptional regulation are typical features of cancer. RNA always plays a key role in these processes. Human transcripts contain many RNAs without long open reading frames (ORF, > 100 aa) and that are more than 200 bp in length. They are usually regarded as long non-coding RNA (lncRNA) which play an important role in cancer regulation, including chromatin remodeling, transcriptional regulation, translational regulation and as miRNA sponges. With the advancement of ribosome profiling and sequencing technologies, increasing research evidence revealed that some ORFs in lncRNA can also encode peptides and participate in the regulation of multiple organ tumors, which undoubtedly opens a new chapter in the field of lncRNA and oncology research. In this review, we discuss the biological function of lncRNA in tumors, the current methods to evaluate their coding potential and the role of functional small peptides encoded by lncRNA in cancers. Investigating the small peptides encoded by lncRNA and understanding the regulatory mechanisms of these functional peptides may contribute to a deeper understanding of cancer and the development of new targeted anticancer therapies.

Subdural abscesses are located between the dura mater and the subarachnoid space， which are primarily caused by Staphylococci and Streptococci， etc. Subdural abscesses caused by Salmonella Typhi are extremely rare. In this article， a patient with acquired immunodeficiency syndrome （AIDS） presented with a subdural abscess with fever and headache. Blood culture and next-generation sequencing （NGS） of cerebrospinal fluid were indicative of Salmonella Typhi infection. He was treated with sensitive antibiotics based on drug sensitivity testing combined with surgical drainage， and Salmonella Typhi was cultured in the drainage sample. During 4-month postoperative follow-up， relevant symptoms were mitigated and imaging examination results were normal. This case prompts that intracranial infection caused by Salmonella Typhi is extremely rare， which can occur in immunocompromised population. Blood culture， pus culture and NGS are of significant value in differential diagnosis of Salmonella Typhi infection. After the diagnosis is confirmed， sensitive antibiotics combined with surgical treatment can achieve high efficacy.

The aim of this study was to investigate the role of the Hounsfield unit value of chest CT non-contrast enhanced scan in evaluating the severity of anemia in HIV-infected patients.

Of all malignancies, pancreatic ductal adenocarcinoma (PDAC), constituting 90% of pancreatic cancers, has the worst prognosis. Glycolysis is overactive in PDAC patients and is associated with poor prognosis. Drugs that inhibit glycolysis as well as induce cell death need to be identified. However, glycolysis inhibitors often fail to induce cell death. We here found that FV-429, a derivative of the natural flavonoid wogonin, can induce mitochondrial apoptosis and inhibit glycolysis in PDAC in vivo and in vitro. In vitro, FV-429 inhibited intracellular ATP content, glucose uptake, and lactate generation, consequently leading to mitochondrial dysfunction and apoptosis in PDAC cells. Furthermore, it decreased the expression of PKM2 (a specific form of pyruvate kinase) through the ERK signaling pathway and enhanced PKM2 nuclear translocation. TEPP-46, the activator of PKM2, reversed FV-429-induced glycolysis inhibition and mitochondrial apoptosis in the PDAC cells. In addition, FV-429 exhibited significant tumor suppressor activity and high safety in BxPC-3 cell xenotransplantation models. These results thus demonstrated that FV-429 decreases PKM2 expression through the ERK signaling pathway and enhances PKM2 nuclear translocation, thereby resulting in glycolysis inhibition and mitochondrial apoptosis in PDAC in vitro and in vivo, which makes FV-429 a promising candidate for pancreatic cancer treatment.

Summary: Prostate cancer (PCa) is a serious health concern for men due to its high incidence and mortality rate. The first therapy typically adopted is androgen deprivation therapy (ADT). However, patient response to ADT varies, and 20–30% of PCa cases develop into castration-resistant prostate cancer (CRPC). This article investigates the anti-PCa effect of a drug candidate named GL-V9 and highlights the significant mechanism involving the AKT-hexokinase II (HKII) pathway. In both androgen receptor (AR)-expressing 22RV1 cells and AR-negative PC3 cells, GL-V9 suppressed phosphorylated AKT and mitochondrial location of HKII. This led to glycolytic inhibition and mitochondrial pathway-mediated apoptosis. Additionally, GL-V9 inhibited AR activity in 22RV1 cells and disrupted the feedback activation of AKT signaling in condition of AR inhibition. This disruption greatly increased the anti-PCa efficacy of the AR antagonist bicalutamide. In conclusion, we present a novel anti-PCa candidate and combination drug strategies to combat CRPC by intervening in the AR-AKT-HKII signaling network.

Site-directed mutagenesis was used to improve the catalytic activity of homoserine dehydrogenase (HSD) to reduce its feedback inhibition and repression by metabolites in the pathway. HSD was docked with the substrate homoserine, and its spatial structure was analyzed. Two key sites, Gly25 and Asp61, were selected for site-directed saturation mutation. The activity screening showed that the mutants A61L and G25G had significantly increased enzyme activity when compared to the wild type (WT). The kinetics and enzymatic properties of these two mutants were studied. It was found that compared to the WT enzyme, the Km values of G25G and A61L decreased, the substrate affinity increased, and the enzyme activity increased by 1.21 and 1.35 times, respectively; the n value decreased, and the positive synergy increased. The optimum temperature for A61L and G25G was 40 ℃, the same as that for WT; the optimum pH for A61L and WT was 8.0, which was lower than that (8.5) for G25G. The half-lives of A61L and G25G were 1 h longer and 0.5 h shorter than that of WT, respectively. Low concentrations of K+, Mg2+, and Ca2+ could activate the mutants and WT, while different concentrations of methanol, ethanol, acetonitrile and dimethyl sulfoxide had significantly inhibitory effects on the mutants and WT. At inhibitor concentrations of 1–25 mmol/L, the inhibitory effect was significantly weaker on the mutants than on WT. The mutants G25G and A61L showed improved enzyme activity and weakened allosteric inhibition. This study provides a reference for optimizing the biosynthetic pathway of HSD and constructing strains capable of producing high yield of methionine, threonine and isoleucine.

BackgroundTreating persistent, recurrent, or metastatic cervical cancer remains challenging. Although pembrolizumab, combined with chemotherapy and bevacizumab, offers a promising first-line option, its cost-effectiveness within the Chinese healthcare system has not been established.MethodsA partitioned survival model was constructed using patient data from the KEYNOTE-826 trial. Efficacy, safety, and economic data from both trial and real-world practices were utilized to determine the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) of the treatment strategies. Comprehensive insights were gained through the sensitivity and subgroup analyses.ResultsOver five years, the combination of pembrolizumab, chemotherapy, and bevacizumab offered an additional 1.18 QALYs compared to that provided by standard treatments. This regimen increased the costs by US$ 134,502.57, resulting in an ICER of US$ 114,275.67 per QALY, relative to traditional treatment costs. The ICER for the pembrolizumab regimen was further calibrated to be US$ 52,765.69 per QALY. Both ICER values surpassed China’s established willingness-to-pay threshold. Importantly, subgroup analysis revealed enhanced cost-effectiveness in patients presenting with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥10.ConclusionIntroducing pembrolizumab alongside chemotherapy and bevacizumab may not be a cost-effective primary strategy for advanced cervical cancer against current standards. However, for patients with a PD-L1 CPS ≥10, the therapeutic and economic outcomes could be improved by adjusting the pembrolizumab price.

Microbubble’s mass transfer under external acoustic excitation holds immense potential across various technological fields. However, the current state of acoustic technology faces limitations due to inadequate control over bubble size in liquids under external excitation. Here, we conducted numerical investigations of the mass transfer behavior of microbubbles in liquids under multifrequency acoustic excitations with different frequencies (in the MHz range), pressure amplitudes (in the range of several atmospheric pressures), and amplitude ratios. We identified various pressure threshold regions for the growth of gas bubbles (radii range from a few microns to tens of microns) and observed common intersections between single and multifrequency excitations that enable effective control of the growth intervals and final size of bubbles by adjusting the ratio of pressure amplitude and frequency value. Allocating power to the lower frequency component of multifrequency acoustic excitation is recommended to facilitate mass transfer or diffusion, as small-frequency acoustic excitation has a more significant effect than the higher frequency in the growth region. Our study provides a better understanding of the dynamics of bubbles under complex excitations and has practical implications for developing methods to control and promote bubble-related processes.

ObjectiveEosinophilic cholangitis (EC) is an uncommon form of benign biliary obstruction. It frequently eludes accurate clinical diagnosis, leading to inappropriate treatment methods. It is our aspiration that this clinical report will impart comprehensive insights into EC and, specifically, the critical role of tomographic examination.Case summaryA 34-year-old man was urgently admitted to the hospital due to excruciating abdominal distress persisting for several hours. Following a six-day course of anti-inflammatory therapy, his symptoms displayed marginal improvement, prompting his discharge. He returned to the hospital a month later for re-examination on doctor’s orders. Based on the results of the re-examination, the patient refused steroid hormone shock therapy and subsequently underwent laparoscopic left-lateral hepatic lobectomy in order to confirm the diagnosis. The preoperative absolute counts of eosinophils in the peripheral blood were documented as 2.3 × 109/L, 3.06 × 109/L, and 1.50 × 109/L consecutively; concurrently, the corresponding percentages of eosinophils were quantified at levels of 21.90%, 30.70%, and 19.20%. The subsequent postoperative pathological assessment unveiled EC as the definitive diagnosis. The patient has since remained free from disease recurrence and is presently alive.ConclusionWhen encountering a patient presenting with persistent elevation in absolute eosinophil count in peripheral blood, coupled with imaging manifestations suggestive of intrahepatic periductal inflammation, diagnosis of EC should be highly suspected. The most optimal diagnostic and therapeutic workflow for EC could entail CT-guided liver lesion biopsy, ensued by glucocorticoid pulse therapy, and finally, short-term monitoring utilizing CT or MRI (including T1WI, T2WI, DWI, CEMRI) techniques.

Objective: In order to improve freshness preservation quality of the fresh-cut shiitake mushroom. Methods: Carbon quantum dots were synthesized from dragon fruit peel and ethylenediamine, and characterized for stability and toxicity. Fresh-cut shiitake mushrooms were studied, and stored at 4 ℃ for 10 d after coating with 0.0, 1.5, 3.0 and 4.5 mL/100 mL carbon quantum dots-chitosan （N-CDs/CH） for preservation treatment. During the period of preservation, the weight loss, color difference, soluble solids and polyphenol oxidase were measured every 24 h to evaluate the preservation effect of the composite films. Results: The synthesized N-CDs had the typical characteristics, which had good fluorescence stability, hydroxyl and amino groups on outer surface, and no cytotoxicity. After fresh-cut shiitake mushrooms were treated with different concentrations of N-CDs/CH until the 10th day of storage, 4.5 mL/100 mL N-CDs/CH coating group had weight loss of 3.31%, coloration of 10.32, soluble solids of 4%, and polyphenol oxidase （PPO） activity of 104.65 U/(kg·s), all of which were significantly better than the blank group and other treatment groups （P＜0.05）. Conclusion: The preservation effect at the 4.5 mL/100 mL of N-CDs/CH coating was significantly better than that of blank and others （P＜0.05）. N-CDs/CH coating inhibited water loss and PPO activity, improved color and enhanced the preservation quality of fresh-cut shiitake mushroom.

The development of the four stomachs of yak is closely related to its health and performance, however the underlying molecular mechanisms are largely unknown. Here, we systematically analyzed mRNAs of four stomachs in five growth time points [0 day, 20 days, 60 days, 15 months and 3 years (adult)] of yaks. Overall, the expression patterns of DEmRNAs were unique at 0 d, similar at 20 d and 60 d, and similar at 15 m and adult in four stomachs. The expression pattern in abomasum was markedly different from that in rumen, reticulum and omasum. Short Time-series Expression Miner (STEM) analysis demonstrated that multi-model spectra are drastically enriched over time in four stomachs. All the identified mRNAs in rumen, reticulum, omasum and abomasum were classified into 6, 4, 7, and 5 cluster profiles, respectively. Modules 9, 38, and 41 were the most significant three colored modules. By weighted gene co-expression network analysis (WGCNA), a total of 5,486 genes were categorized into 10 modules. CCKBR, KCNQ1, FER1L6, and A4GNT were the hub genes of the turquoise module, and PAK6, TRIM29, ADGRF4, TGM1, and TMEM79 were the hub genes of the blue module. Furthermore, functional KEGG enrichment analysis suggested that the turquoise module was involved in gastric acid secretion, sphingolipid metabolism, ether lipid metabolism, etc., and the blue module was enriched in pancreatic secretion, pantothenate and CoA biosynthesis, and starch and sucrose metabolism, etc. Our study aims to lay a molecular basis for the study of the physiological functions of rumen, reticulum, omasum and abomasum in yaks. It can further elucidate the important roles of these mRNAs in regulation of growth, development and metabolism in yaks, and to provide a theoretical basis for age-appropriate weaning and supplementary feeding in yaks.