Next-generation red ultra-bright fluorescent dyes for nuclear imaging and peripheral blood leukocytes sorting.

The nucleus is a membrane-bound organelle in eukaryotic cells and plays a crucial role in cellular processes. Visualizing nuclear morphology is essential for investigating nuclear functions and understanding the relationship between nuclear morphological alterations and multiple diseases. Fluorescent dyes have been developed to visualize nuclear morphology, but the selection of red nuclear-labeling fluorescent dyes remains limited (high price, unknown structure, or high toxicity). Herein, we have developed a red ultra-bright nuclear-targeted dye, BPC1, through the engineering of unsymmetrical cyanine dyes derived from D-π-A systems. BPC1 exhibits ultrahigh fluorescence brightness and exceptional cell permeability, and selectively stains nuclear DNA rather than mitochondrial DNA, enabling the visualization of the nucleus in diverse cells at extremely low doses (100 nM) and laser power (0.8 µW). Furthermore, BPC1 is utilized for nuclear staining in blood cells, aiding in the distinct visualization of the white blood cell nucleus and facilitating the identification and enumeration of various leukocyte types. Our study implies considerable commercial potential for BPC1 and underscores its capacity to serve as a powerful tool in life sciences and cell biology research.

Comparison of zuberitamab plus CHOP versus rituximab plus CHOP for the treatment of drug-naïve patients diagnosed with CD20-positive diffuse large B-cell lymphoma: a phase 3 trial.

BACKGROUND: In patients with untreated CD20-positive diffuse large B-cell lymphoma (DLBCL), a phase 3 trial was carried out to evaluate the efficacy and safety of zuberitamab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; Hi-CHOP) versus rituximab plus CHOP (R-CHOP) treatment regimens. METHODS: In a 2:1 ratio, eligible patients were assigned randomly to receive treatment of six cycles of either 375 mg/m2 zuberitamab or rituximab together with conventional CHOP chemotherapy. The objective response rate (ORR) at C6D50 served as the primary endpoint, and a non-inferiority margin of 10% was established. The secondary endpoints included the complete response (CR) rate at C6D50, duration of response (DOR), progression-free survival (PFS) and event-free survival (EFS) judged by blinded-independent review committee (BIRC), overall survival (OS) and safety outcomes. RESULTS: Of the 487 randomized patients, 423 patients including 287 in the Hi-CHOP and 136 in the R-CHOP groups completed the C6D50 assessment. For the full analysis set (FAS) and per-protocol set (PPS), BIRC-assessed ORR at C6D50 for the Hi-CHOP and R-CHOP groups were 83.5% versus 81.4% and 95.3% versus 93.7%, respectively. The non-inferiority was confirmed as the lower limit of the two-sided 95% CI for the intergroup differences of -5.2% and -3.3%; both were >-10% in the FAS and PPS. The BIRC-assessed CR rate of Hi-CHOP was significantly higher in PPS (85.7% vs 77.3%, p=0.038), but comparable in FAS (75.2% vs 67.9%, p=0.092). After a median follow-up of 29.6 months, patients in the Hi-CHOP group had a slight advantage with regard to the DOR (HR 0.74, p=0.173), PFS (HR 0.67, p=0.057), EFS (HR 0.90, p=0.517) and OS (HR 0.60, p=0.059). Patients with the germinal-center B cell-like subtype who received Hi-CHOP exhibited statistically significant improvements in ORR (p=0.034) and CR rate (p=0.038) at C6D50, EFS (p=0.046) and OS (p=0.014). Treatment-emergent adverse event occurrence rates were comparable across groups (all p>0.05). Infusion-related responses occurred more often in the Hi-CHOP group (32.1% vs 19.9%, p=0.006), all of grade 1-3 severity. CONCLUSIONS: Zuberitamab (375 mg/m2) plus CHOP was non-inferior to R-CHOP regarding ORR but exhibited a higher CR rate and was well tolerated in CD20-positive, previously untreated Chinese patients with DLBCL. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2000040602, retrospectively registered.

Human umbilical cord mesenchymal stem cells toxicity and allergy effects: In vivo assessment.

OBJECTIVE: Human umbilical cord mesenchymal stem cells (hUCMSCs) hold significant promise across various clinical applications. Therefore, regulatory requirements necessitate a thorough investigation of the hUCMSCs safety before clinical trials and potential allergic reactions after transplantation. METHODS: Abnormal toxicity test employed mice and guinea pigs dosed daily at 0.5×106 cells and 5×106 cells, respectively for 7 days. Acute toxicity test employed low, medium, and high doses of hUCMSCs injected into mice once, followed by observations for 23 days. In systemic allergy test, guinea pigs received low and high dose of hUCMSCs, with sensitization and excitation stages at day 14 and 21, respectively. RESULTS: The abnormal toxicity test of hUCMSC injections revealed no abnormal reactions over a seven-day observation period, indicating the safety of this administration route. In acute toxicity studies, the high-dose hUCMSCs group resulted in fatalities due to pulmonary embolism. Conversely, the low-dose group exhibited no toxic reactions or deaths. The maximum tolerated dose was determined to be >2×107 cells/kg. Systemic active allergy test showed that high doses of hUCMSC intravenous injections did not induce allergic reactions. CONCLUSION: This research affirms hUCMSC injections meet safety standards for clinical cell therapy, emphasizing their safe and promising clinical utility.

The SCR-17 and SCR-18 glycans in human complement factor H enhance its regulatory function.

Human complement factor H (CFH) plays a central role in regulating activated C3b to protect host cells. CFH contain 20 short complement regulator (SCR) domains and eight N-glycosylation sites. The N-terminal SCR domains mediate C3b degradation while the C-terminal CFH domains bind to host cell surfaces to protect these. Our earlier study of Pichia-generated CFH fragments indicated a self-association site at SCR-17/18 that comprises a dimerization site for human factor H. Two N-linked glycans are located on SCR-17 and SCR-18. Here, when we expressed SCR-17/18 without glycans in an Escherichia coli system, analytical ultracentrifugation showed that no dimers were now formed. To investigate this novel finding, full-length CFH and its C-terminal fragments were purified from human plasma and Pichia pastoris respectively, and their glycans were enzymatically removed using PNGase F. Using size-exclusion chromatography, mass spectrometry, and analytical ultracentrifugation, SCR-17/18 from Pichia showed notably less dimer formation without its glycans, confirming that the glycans are necessary for the formation of SCR-17/18 dimers. By surface plasmon resonance, affinity analyses interaction showed decreased binding of deglycosylated full-length CFH to immobilized C3b, showing that CFH glycosylation enhances the key CFH regulation of C3b. We conclude that our study revealed a significant new aspect of CFH regulation based on its glycosylation and its resulting dimerization.

Predict the Drug-Drug Interaction of a Novel PI3Kα/δ Inhibitor, TQ-B3525, and Its Two Metabolites Using Physiologically Based Pharmacokinetic Modeling.

A novel dual PI3K α/δ inhibitor, TQ-B3525, has been developed for the targeted treatment of lymphoma and solid tumors. TQ-B3525 is primarily metabolized by CYP3A4 and FOM3, while also serving as a substrate for the P-glycoprotein transporter. The aim of this study was to anticipate the drug-drug interaction (DDI) of TQ-B3525 and its two metabolites with CYP3A4 enzyme potent inducer (rifampicin) and CYP3A4/P-gp inhibitor (itraconazole) utilizing a physiologically based pharmacokinetic (PBPK) modeling approach. Clinical data from healthy and cancer patient adults were employed to construct and evaluate the PBPK model for TQ-B3525, M3, and M8-3. Models involving rifampicin combined with midazolam, itraconazole combined with midazolam or digoxin were utilized to showcase the robustness of evaluating DDI effects. The simulated drug exposure of TQ-B3525, M3, and M8-3 in healthy and patient adults were consistent with clinical data, and the mean fold error values were within the acceptable ranges. The simulated results of positive substrates correspond to those reported in the literature. Co-administration with rifampicin reduces Cmax and AUC of TQ-B3525 to 76.1% and 46.0%, while increasing the levels of M3 and M8-3. With itraconazole, Cmax and AUC of TQ-B3525 rise to 131% and 204%, but decrease substantially for M3 and M8-3. PBPK model simulation results showed that the systemic exposure of TQ-B3525 was significantly affected when co-administered with CYP3A4/P-gp inducers and inhibitors. This indicates that the combination with strong inducers and inhibitors should be carefully avoided or adjust the dosage of TQ-B3525 in clinic.

Acidic Pepsin Affects Laryngeal Carcinoma Cell Growth and Invasion Through Glycolysis.

OBJECTIVE: The pathogenic mechanism underlying the effects of acidic pepsin in laryngeal cancer remains unclear. This study investigated whether acidic pepsin influences Glut-1 expression and glycolytic activity in laryngeal carcinoma cells and whether it plays a role in the growth and migration of these cells through glycolysis. STUDY DESIGN: In vitro study. SETTING: A university-affiliated hospital. METHODS: Laryngeal carcinoma TU 212 and TU 686 cells were treated with acidic pepsin and 2-deoxy-d-glucose (2-DG), then transfected with Glut-1 small interfering RNA (siRNA). Glucose uptake was detected by a radioimmunoassay counter, lactate secretion was detected by a lactic acid kit, and Glut-1 expression was detected by western blotting. Cell viability, migration and invasion, and clonal formation were assessed using the Cell Counting Kit-8, Transwell chamber, and clonal formation assays, respectively. RESULTS: Acidic pepsin significantly increased Glut-1 expression in laryngeal carcinoma cells compared with the control group (P < .01). It also significantly enhanced 18F-fluorodeoxyglucose (Cin/Cout) uptake, lactate secretion, cell viability, migration, invasion, and clonal formation in laryngeal carcinoma cells compared with the control group (P < .01). The glycolytic inhibitor 2-DG and Glut-1 siRNA significantly reversed the effects of acidic pepsin on laryngeal carcinoma cells (P < .01). CONCLUSION: Acidic pepsin enhances the growth and migration of laryngeal carcinoma cells by upregulating Glut-1, thus promoting glycolysis.

Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in aging and obesity.

Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

Research on the signaling pathway and the related mechanism of traditional Chinese medicine intervention in chronic gastritis of the "inflammation-cancer transformation".

Objective: The aim of this study is to uncover the traditional Chinese medicine (TCM) treatments for chronic gastritis and their potential targets and pathways involved in the "inflammation-cancer" conversion in four stages. These findings can provide further support for future research into TCM and its active components. Materials and methods: The literature search encompassed PubMed, Web of Science, Google Scholar, CNKI, WanFang, and VIP, employing keywords such as "chronic gastritis", "gastric cancer", "traditional Chinese medicine", "medicinal herb", "Chinese herb", and "natural plant". Results: Herbal remedies may regulate the signaling pathways linked to the advancement of chronic gastritis. Under the multi-target and multi-pathway independent or combined reaction, the inflammatory microenvironment may be enhanced, leading to repair of damaged gastric mucosal cells, buffering the progress of mucosal atrophic degeneration via the decrease of inflammatory factor expression, inhibition of oxidative stress-induced damage, facilitation of microvascular neovascularization in the gastric mucosa and regulation of the processes of gastric mucosal cell differentiation and proliferation. Simultaneously, the decreased expression of inflammatory factors may impact the expression of associated oncogenes and regulate the malignant proliferation of cells, thereby achieving the treatment and prevention objectives of gastric cancer through the reduction of cell metastasis and apoptosis. Conclusion: Chinese medicine formulations and individual drugs can be utilised at various stages of the "inflammation-cancer" progression of chronic gastritis to prevent and treat gastric cancer in a multi-level, multi-targeted, and multi-directional fashion. This can provide guidance for the accurate application of medicines during different stages of "inflammation-cancer" transformation. New insights into the mechanism of inflammation-cancer transformation and the development of novel drugs for chronic gastritis can be gained through an extensive investigation of TCM treatment in this condition.

Pharmacokinetics, mass balance, and metabolism of [14C]envonalkib (TQ-B3139), a novel ALK tyrosine kinase inhibitor, in healthy Chinese subjects.

PURPOSE: Envonalkib (TQ-B3139) is a novel, potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor used to treat ALK-positive non-small cell lung cancer. This phase I mass balance study investigated the pharmacokinetics, metabolism, and excretion of 14C-radiolabeled envonalkib in healthy Chinese male subjects. METHODS: A single oral dose of 600 mg (150 µCi) [14C]envonalkib was administered to healthy male subjects under fasted state. Samples of blood, urine and feces were collected for quantitative determination of total radioactivity and unchanged envonalkib, and the metabolites identification. RESULTS: After dosing, the median Tmax of radioactivity was 4 h and the mean t1/2 was 65.2 h in plasma. The exposure of total radioactivity was much higher than that of unchanged envonalkib in plasma. The mean total recovery of the radiolabeled dose was 93.93% over 504 h post-dose, with 15.23% in urine and 78.71% in feces. Envonalkib underwent extensive metabolism and a total of 15 metabolites were identified in plasma, urine, and feces. Unchanged envonalkib and its major metabolite M315 were the main components in plasma, accounting for 20.37% and 33.33% of total plasma radioactivity. In urine, O-dealkylation metabolite M315 was the major component accounted for 7.98% of dose. In feces, 16.01% of dose was excreted as cysteine conjugate M434-1. Envonalkib was well tolerated and there were no serious adverse events observed in the study. CONCLUSION: Envonalkib was extensively metabolized prior to excretion and eliminated primarily as metabolites via feces.

The decreased astrocyte-microglia interaction reflects the early characteristics of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease often associated with olfactory dysfunction. Aß is a typical AD hall marker, but Aß-induced molecular alterations in olfactory memory remain unclear. In this study, we used a 5xFAD mouse model to investigate Aß-induced olfactory changes. Results showed that 4-month-old 5xFAD have olfactory memory impairment accompanied by piriform cortex neuron activity decline and no sound or working memory impairment. In addition, synapse and glia functional alteration is consistent across different ages at the proteomic level. Microglia and astrocyte specific proteins showed strong interactions in the conserved co-expression network module. Moreover, this interaction declines only in mild cognitive impairment patients in human postmortem brain proteomic data. This suggests that astrocytes-microglia interaction may play a leading role in the early stage of Aß-induced olfactory memory impairment, and the decreasing of their synergy may accelerate the neurodegeneration.

Fibrous MXene Synapse-Based Biomimetic Tactile Nervous System for Multimodal Perception and Memory.

Biomimetic tactile nervous system (BTNS) inspired by organisms has motivated extensive attention in wearable fields due to its biological similarity, low power consumption, and perception-memory integration. Though many works about planar-shape BTNS are developed, few researches could be found in the field of fibrous BTNS (FBTNS) which is superior in terms of strong flexibility, weavability, and high-density integration. Herein, a FBTNS with multimodal sensibility and memory is proposed, by fusing the fibrous poly lactic acid (PLA)/Ag/MXene/Pt artificial synapse and MXene/EMIMBF4 ionic conductive elastomer. The proposed FBTNS can successfully perceive external stimuli and generate synaptic responses. It also exhibits a short response time (23 ms) and low set power consumption (17 nW). Additionally, the proposed device demonstrates outstanding synaptic plasticity under both mechanical and electrical stimuli, which can simulate the memory function. Simultaneously, the fibrous devices are embedded into textiles to construct tactile arrays, by which biomimetic tactile perception and temporary memory functions are successfully implemented. This work demonstrates the as-prepared FBTNS can generate biomimetic synaptic signals to serve as artificial feeling signals, it is thought that it could offer a fabric electronic unit integrating with perception and memory for Human-Computer interaction, and has great potential to build lightweight and comfortable Brain-Computer interfaces.

Early delivery of human umbilical cord mesenchymal stem cells improves healing in a rat model of Achilles tendinopathy.

Objective: This study aimed to explore the efficacy and optimal delivery time of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating collagenase-induced Achilles tendinopathy. Methods: Achilles tendinopathy in rats at early or advanced stages was induced by injecting collagenase I into bilateral Achilles tendons. A total of 28 injured rats were injected with a hUC-MSC solution or normal saline into bilateral tendons twice and sampled after 4 weeks for histological staining, gene expression analysis, transmission electron microscope assay and biomechanical testing analysis. Results: The results revealed better histological performance and a larger collagen fiber diameter in the MSC group. mRNA expression of TNF-α, IL-1ß and MMP-3 was lower after MSC transplantation. Early MSC delivery promoted collagen I and TIMP-3 synthesis, and strengthened tendon toughness. Conclusion: hUC-MSCs demonstrated a therapeutic effect in treating collagenase-induced Achilles tendinopathy, particularly in the early stage of tendinopathy.

Efficacy, Safety, and Population Pharmacokinetics of MW032 Compared With Denosumab for Solid Tumor-Related Bone Metastases: A Randomized, Double-Blind, Phase 3 Equivalence Trial.

Importance: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor-related bone metastases. Objectives: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor-related bone metastases based on a large-scale head-to-head study. Design, Setting, and Participants: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab. Interventions: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49. Main Outcomes and Measures: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr). Results: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was -72.0% (95% CI, -73.5% to -70.4%) in the MW032 group and -72.7% (95% CI, -74.2% to -71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of -1.27 and -1.30, or a difference of 0.02. The 90% CI for the difference (-0.04 to 0.09) was within the equivalence margin (-0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, -0.06 to 0.09), -0.02 (95% CI, -0.09 to 0.06), -0.05 (95% CI, -0.13 to 0.03) and 0.001 (95% CI, -0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were -0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, -0.07 to 0.07), -0.085 (95% CI, -0.18 to 0.01), -0.09 (95% CI, -0.20 to 0.02), and -0.13 (95% CI, -0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (-1.4%; 95% CI, -5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups. Conclusions and Relevance: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors. Trial Registration: ClinicalTrials.gov Identifier: NCT04812509.

Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study.

HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer.

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.

Establishment and validation of novel nomograms to predict muscle quality in colorectal cancer patients.

OBJECTIVES: The skeletal muscle mass index and skeletal muscle radiodensity have promise as specific diagnostic indicators for muscle quality. However, the difficulties in measuring low skeletal muscle mass index and low skeletal muscle radiodensity limit their use in routine clinical practice, impeding early screening and diagnosis. The objective of this study is to develop a nomogram that incorporates preoperative factors for predicting low skeletal muscle mass index and low skeletal muscle radiodensity. METHODS: A total of 1692 colorectal cancer patients between 2015 and 2021 were included. The patients were randomly divided into a training cohort (n = 1353) and a validation cohort (n = 339). Nomogram models were calibrated using the area under the curve, calibration curves, and the Hosmer-Lemeshow test to assess their predictive ability. Finally, a decision curve was applied to assess the clinical usefulness. RESULTS: In a prediction model for low skeletal muscle mass index, age, body mass index, and grip strength were incorporated as variables. For low skeletal muscle radiodensity, age, sex, body mass index, serum hemoglobin level, and grip strength were included as predictors. In the training cohort, the area under the curve value for low skeletal muscle mass index was 0.750 (95% CI, 0.726-0.773), whereas for low skeletal muscle radiodensity, it was 0.763 (95% CI, 0.739-0.785). The Hosmer-Lemeshow test confirmed that both models fit well in both cohorts. Decision curve analysis was applied to assess the clinical usefulness of the model. CONCLUSIONS: The incorporation of preoperative factors into the nomogram-based prediction model represents a significant advancement in the muscle quality assessment. Its implementation has the potential to early screen patients at risk of low skeletal muscle mass index and low skeletal muscle radiodensity.

Blood-derived product therapies for SARS-CoV-2 infection and long COVID.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of large-scale transmission and has caused the coronavirus disease 2019 (COVID-19) pandemic. Patients with COVID-19 may experience persistent long-term health issues, known as long COVID. Both acute SARS-CoV-2 infection and long COVID have resulted in persistent negative impacts on global public health. The effective application and development of blood-derived products are important strategies to combat the serious damage caused by COVID-19. Since the emergence of COVID-19, various blood-derived products that target or do not target SARS-CoV-2 have been investigated for therapeutic applications. SARS-CoV-2-targeting blood-derived products, including COVID-19 convalescent plasma, COVID-19 hyperimmune globulin, and recombinant anti-SARS-CoV-2 neutralizing immunoglobulin G, are virus-targeting and can provide immediate control of viral infection in the short term. Non-SARS-CoV-2-targeting blood-derived products, including intravenous immunoglobulin and human serum albumin exhibit anti-inflammatory, immunomodulatory, antioxidant, and anticoagulatory properties. Rational use of these products can be beneficial to patients with SARS-CoV-2 infection or long COVID. With evidence accumulated since the pandemic began, we here summarize the progress of blood-derived product therapies for COVID-19, discuss the effective methods and scenarios regarding these therapies, and provide guidance and suggestions for clinical treatment.

Clusterin is a Potential Therapeutic Target in Alzheimer's Disease.

In recent years, Clusterin, a glycosylated protein with multiple biological functions, has attracted extensive research attention. It is closely associated with the physiological and pathological states within the organism. Particularly in Alzheimer's disease (AD) research, Clusterin plays a significant role in the disease's occurrence and progression. Numerous studies have demonstrated a close association between Clusterin and AD. Firstly, the expression level of Clusterin in the brain tissue of AD patients is closely related to pathological progression. Secondly, Clusterin is involved in the deposition and formation of ß-amyloid, which is a crucial process in AD development. Furthermore, Clusterin may affect the pathogenesis of AD through mechanisms such as regulating inflammation, controlling cell apoptosis, and clearing pathological proteins. Therefore, further research on the relationship between Clusterin and AD will contribute to a deeper understanding of the etiology of this neurodegenerative disease and provide a theoretical basis for developing early diagnostic and therapeutic strategies for AD. This also makes Clusterin one of the research focuses as a potential biomarker for AD diagnosis and treatment monitoring.

Oreocharis oriolus, a new species of Gesneriaceae in a sclerophyllous oak community from Yunnan, Southwest China.

Oreocharis oriolus, a new species of Gesneriaceae in a sclerophyllous oak community from Yunnan, Southwest China, is described and illustrated. Morphologically, it resembles both O. forrestii and O. georgei, while it is distinct in combined characters of wrinkled leaves, peduncle and pedicel covered with whitish and egladular villous hairs, bract lanceolate and nearly glabrescent adaxially, and staminode absent. Molecular phylogenetic analysis based on nuclear ribosomal internal transcribed spacer (nrITS) and chloroplast DNA fragment (trnL-F) of 61 congeneric species also supported O. oriolus as a new species while it was nested with O. delavayi. It was currently assessed as 'Critically Endangered' (CR) regarding to its small-sized population and narrow distribution following the IUCN categories and criteria.

GPR43 protects human A16 cardiomyocytes against hypoxia/reoxygenation injury by regulating nesfatin1.

BACKGROUND: The purpose of this study is to investigate the regulatory role of G coupled-protein receptor 43 (GPR43) during myocardial ischemia/reperfusion (I/R) injury and to explore the relevant molecular mechanism. MATERIALS AND METHODS: AC16 hypoxia/reoxygenation (H/R) model was established to simulate I/R injury in vitro. Gain- and loss-of-function experiments were conducted to regulate GPR43 or nesfatin1 expression. Cell viability and apoptosis was examined adopting CCK-8 and TUNEL assays. Commercial kits were applied for detecting ROS and inflammatory cytokines. Quantitative real-time PCR (qRT-PCR) and western blotting were conducted to measure the expression level of critical genes and proteins. RESULTS: GPR43 was downregulated in H/R-mediated AC16 cells. GPR43 overexpression or the GPR43 agonist greatly inhibited H/R-induced cell viability loss, cell apoptosis, and excessive production of ROS and pro-inflammatory cytokines in AC16 cardiomyocytes. Co-immunoprecipitation (Co-IP) assay identified an interaction between GPR43 and nesfatin1, and GPR43 could positively regulate nesfatin1. In addition, the protective role of GPR43 against H/R injury was partly abolished upon nesfatin1 knockdown. Eventually, GPR43 could inhibit H/R-stimulated JNK/P38 MAPK signaling in AC16 cells, which was also hindered by nesfatin1 knockdown. CONCLUSIONS: Our findings demonstrated the protective role of GPR43 against H/R-mediated cardiomyocytes injury through up-regulating nesfatin1, providing a novel target for the prevention and treatment of myocardial I/R injury.