Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma.

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Oxycodone vs. sufentanil combined with quadratus lumborum block vs. transverse abdominis plane block in laparoscopic major gastrointestinal surgery: A randomized factorial trial protocol.

Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery. Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0-24 h and 24-48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay. Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766).

The relationships between obesity and epilepsy: A systematic review with meta-analysis.

OBJECTIVE: There is ongoing debate regarding the association between epilepsy and obesity. Thus, the aim of this study was to examine the correlation between epilepsy and obesity. METHOD: This study adhered to the PRISMA guidelines for systematic reviews and meta-analyses. On The Prospero website, this study has been successfully registered (CRD42023439530), searching electronic databases from the Cochr-ane Library, PubMed, Web of Sciences and Embase until February 10, 2024.The search keywords included "Epilepsy", "Obesity", "Case-Control Studies", "cohort studies", "Randomized Controlled Trial" and "Cross-Sectional Studies". The medical subject headings(MeSH) of PubMed was utilized to search for relevant subject words and free words, and a comprehensive search strategy was developed. Two reviewers conducted article screening, data extraction and bias risk assessment in strict accordance with the predefined criteria for including and excluding studies. The predefined inclusion criteria were as follows: 1) Inclusion of case-control, cohort, randomized controlled trial, and cross-sectional studies; 2) Segregation of subjects into epileptic patients and healthy controls; 3)Obesity as the outcome measure; 4) Availability of comprehensive data; 5) Publication in English. The exclusion criteria were as follows: 1) Exclusion of animal experiments, reviews, and other types of studies; 2) Absence of a healthy control group; 3) Incomplete data; 4) Unextractable or unconvertible data; 5) Low quality, indicated by an Agency for Healthcare Research and Quality(AHRQ) score of 5 or lower,or a Newcastle-Ottawa Scale (NOS) score less than 3. The subjects included in the study included adults and children, and the diagnostic criteria for obesity were used at different ages. In this study, obesity was defined as having a body mass index(BMI) of 25 kg/m2 or higher in adults and being above the 85th percentile of BMI for age in children. We used obesity as an outcome measure for meta-analysis using RevMan, version 5.3. RESULTS: A meta-analysis was conducted on a total of 17 clinical studies, which involved 5329 patients with epilepsy and 480837 healthy controls. These studies were selected from a pool of 1497 articles obtained from four electronic databases mentioned earlier. Duplicate studies were removed based on the search strategies employed. No significant heterogeneity was observed in the outcome measure of obesity in epileptic patients compared with healthy controls(p = 0.01,I2 = 49%). Therefore, a fixed effects model was utilized in this study. The findings revealed a significant difference in obesity prevalence between patients with epilepsy and healthy controls(OR = 1.28, 95%CI: 1.20-1.38, p<0.01). CONCLUSION: The results of this meta-analysis indicate that epilepsy patients are more prone to obesity than healthy people, so we need to pay attention to the problem of post-epilepsy obesity clinically. Currently, there is a scarcity of largescale prospective studies. Additional clinical investigations are warranted to delve deeper into whether obesity is a comorbidity of epilepsy and whether obesity can potentially trigger epilepsy.

[Inflammatory factors and prostate cancer: Two-sample Mendelian randomization analysis].

OBJECTIVE: To evaluate the potential causal relationship between inflammatory factors and PCa using the two-sample Mendelian randomization (MR) method. METHODS: We selected summary statistics of genome-wide association studies (GWAS) (n = 14 824) on 91 inflammatory factors, with PCa as the outcome in the latest 9th edition of FinnGen database for MR analysis. We evaluated the causal relationship between inflammatory factors and PCa using the odds ratio (OR) and 95% confidence interval (CI) of such regression models as inverse variance weighting (IVW), MR-Egger regression, simple mode (SM), weighted mode (WM) and weighted median estimator (WME), with IVW as the main statistical method for this study. We further verified the results of MR by Bayesian analysis, and evaluated the heterogeneity of genetic instrumental variables, pleiotropic effects and sensitivity of single nucleotide polymorphisms (SNP) as instrumental variables to the exposure-outcome relationship by Cochran's Q test, MR-Egger intercept test and leave-one-out cross validation. RESULTS: IVW showed that among the 91 inflammatory factors, interleukin-22 receptor A1 (IL-22RA1) and sulfotransferase 1A1 (ST1A1) were correlated positively with the risk of PCa； IL-22RA1：IVW（OR ［95% CI］: 1.12 ［1.00－1.25］, P = 0.04）；ST1A1：IVW（OR ［95% CI］: 1.08 (1.00－1.16), P = 0. 03）, while Chemokine ligand 11 (CXCL11) and interleukin 17 A (IL-17 A) negatively with the risk of PCa； CXCL11：IVW（OR ［95% CI］: 0.88 ［0.81－0.95］, P = 0.00）；IL-17A：IVW（OR ［95% CI］: 0.91 ［0.84－0.98］, P = 0.02）. No potential horizontal pleiotropy was detected by MR-Egger intercept analysis (P > 0.05, IL-22RA1 = 0.885, ST1A1 = 0.949, CXCL11 = 0.391, IL-17A = 0.884), nor biased SNPs in the MR pleiotropy residual sum and outlier (MR-PRESSO) test (P > 0.05, IL-22RA1 = 0.479, ST1A1 = 0.629, CXCL11 = 0.326, IL-17A = 0.444), or heterogeneity P > 0.05, IL-22RA1 = 0.543, ST1A1 = 0.677, CXCL11 = 0.336, IL-17A = 0.494). Leave-one-out sensitivity analysis indicated no significant impact of individual SNP sites on the overall causal relationship prediction, suggesting the reliable results of analysis. CONCLUSION: Among the 91 inflammatory factors, IL-22RA1 and ST1A1 have a positive causal relationship, while CXCL11 and IL-17A have a negative causal relationship with PCa.

Deacetylation of HnRNP U mediated by sirtuin1 ameliorates aged rat with liver fibrosis via inhibiting p53-related senescence and NLRP3-related inflammation.

Senescence represents a major risk factor promoting liver fibrosis progression. Sirtuin 1 (SIRT1), an essential regulator of cellular senescence, may be involved in developing liver fibrosis. However, the role and mechanism of SIRT1 in liver fibrosis development were largely unknown. We constructed the liver fibrosis in aged rats induced by carbon tetrachloride (CCl4) and then transfected with GFP-SIRT1 adenoviral vectors. After that, we performed acetylomic analysis of liver tissue in aged rats to identify potential substrates of SIRT1. Furthermore, replicative senescent rat hepatocytes were pretreated with siRNA HnRNP U, SIRT1 adenoviral vectors, resveratrol, and siRNA SIRT1, following stimulation with H2O2. We found that the protein levels of SIRT1 and HnRNP U were down-regulation in aged rat liver fibrotic tissues, with an accumulation of NLRP3 inflammasome and activation of the p53/p21 pathway in liver tissue, as well as an increased level of plasma IL-1ß secretion. In comparison, these effects were reversed by overexpressing SIRT1 with adenoviral vectors. Acetylation of HnRNP U and its sites at K28 and K787 might be potential targets for SIRT1-mediated liver fibrosis in aged rats. Silencing HnRNP U reduced H2O2-induced up-regulation expression of p53, p21, and NLRP3 inflammasome at protein levels. Additionally, H2O2 induced high acetylation of HnRNP U in senescent hepatocytes, whereas overexpressing SIRT1 with adenoviral vectors and resveratrol deacetylate HnRNP U to inhibit NLRP3 inflammasome and the p53/p21 pathway. Besides, the silence of SIRT1 aggravated H2O2-induced p53-related senescence and NLRP3-related inflammation in senescent hepatocytes. Our findings suggested that deacetylation of HnRNPU mediated by SIRT1 attenuated liver fibrosis in the elderly by inhibiting p53/p21 pathway and NLRP3-related inflammation.

Self-Driven, Monopolar Electrohydrodynamic Printing via Dielectric Nanoparticle Layer.

Electrohydrodynamic printing holds both ultrahigh-resolution fabrication capability and unmatched ink-viscosity compatibility yet fails on highly insulating thick/irregular substrates. Herein, we proposed a single-potential driven electrohydrodynamic printing process with submicrometer resolution on arbitrary nonconductive targets, regardless of their geometric shape or sizes, via precoating with an ultrathin dielectric nanoparticle layer. Benefiting from the favorable Maxwell-Wagner polarization, the reversely polarized spot brought about a significant drop (∼57% for ceramics) in the operation voltage as its induced electric field and a negligible residual charge accumulation. Thus, ordered micro/nanostructures with line widths down to 300 nm were directly written at a stage speed as low as 5 mm/s, and silver features with width of ∼2 µm or interval of ∼4 µm were achieved on insulating substrates separately. Flexible sensors and curved heaters were then high-precision printed and demonstrated successfully, presenting this technique with huge potential for fabricating flexible/conformal electronics on arbitrary 3D structures.

Biomolecule-grafted GO enhanced the mechanical and biological properties of 3D printed PLA scaffolds with TPMS porous structure.

Graphene oxide (GO) exhibits excellent mechanical strength and modulus. However, its effectiveness in mechanically reinforcing polymer materials is limited due to issues with interfacial bonding and dispersion arising from differences in the physicochemical properties between GO and polymers. Surface modification using coupling agents is an effective method to improve the bonding problem between polymer and GO, but there may be biocompatibility issues when used in the biomedical field. In this study, the biomolecule L-lysine, was applied to improve the interfacial bonding and dispersion of GO in polylactic acid (PLA) without compromising biocompatibility. The PLA/L-lysine-modified GO (PLA/L-GO) bone scaffold with triply periodic minimal surface (TPMS) structure was prepared using fused deposition modeling (FDM). The FTIR results revealed successful grafting of L-lysine onto GO through the reaction between their -COOH and -NH2 groups. The macroscopic and microscopic morphology characterization indicated that the PLA/L-GO scaffolds exhibited an characteristics of dynamic diameter changes, with good interlayer bonding. It was noteworthy that the L-lysine modification promoted the dispersion of GO and the interfacial bonding with the PLA matrix, as characterized by SEM. As a result, the PLA/0.1L-GO scaffold exhibited higher compressive strength (13.2 MPa) and elastic modulus (226.8 MPa) than PLA/0.1GO. Moreover, PLA/L-GO composite scaffold exhibited superior biomineralization capacity and cell response compared to PLA/GO. In summary, L-lysine not only improved the dispersion and interfacial bonding of GO with PLA, enhancing the mechanical properties, but also improved the biological properties. This study suggests that biomolecules like L-lysine may replace traditional modifiers as an innovative bio-modifier to improve the performance of polymer/inorganic composite biomaterials.

[Research progress of deep learning applications in mass spectrometry imaging data analysis].

Mass spectrometry imaging (MSI) is a promising method for characterizing the spatial distribution of compounds. Given the diversified development of acquisition methods and continuous improvements in the sensitivity of this technology, both the total amount of generated data and complexity of analysis have exponentially increased, rendering increasing challenges of data postprocessing, such as large amounts of noise, background signal interferences, as well as image registration deviations caused by sample position changes and scan deviations, and etc. Deep learning (DL) is a powerful tool widely used in data analysis and image reconstruction. This tool enables the automatic feature extraction of data by building and training a neural network model, and achieves comprehensive and in-depth analysis of target data through transfer learning, which has great potential for MSI data analysis. This paper reviews the current research status, application progress and challenges of DL in MSI data analysis, focusing on four core stages: data preprocessing, image reconstruction, cluster analysis, and multimodal fusion. The application of a combination of DL and mass spectrometry imaging in the study of tumor diagnosis and subtype classification is also illustrated. This review also discusses trends of development in the future, aiming to promote a better combination of artificial intelligence and mass spectrometry technology.

Construction of Metal-Organic Framework as a Novel Platform for Ratiometric Determination of Cyanide.

Metal-organic frameworks (MOFs) are frequently utilized as sensing materials. Unfortunately, the low conductivity of MOFs hinder their further application in electrochemical determination. To overcome this limitation, a novel modification strategy for MOFs was proposed, establishing an electrochemical determination method for cyanides in Baijiu. Co and Ni were synergistically used as the metal active centers, with meso-Tetra(4-carboxyphenyl)porphine (TCPP) and Ferrocenecarboxylic acid (Fc-COOH) serving as the main ligands, synthesizing Ni/Co-MOF-TCPP-Fc through a hydrothermal method. The prepared MOF exhibited improved conductivity and stable ratio signals, enabling rapid and sensitive determination of cyanides. The screen-printed carbon electrodes (SPCE) were suitable for in situ and real-time determination of cyanide by electrochemical sensors due to their portability, low cost, and ease of mass production. A logarithmic linear response in the range of 0.196~44 ng/mL was demonstrated by this method, and the limit of detection (LOD) was 0.052 ng/mL. Compared with other methods, the sensor was constructed by a one-step synthesis method, which greatly simplifies the analysis process, and the determination time required was only 4 min. During natural cyanide determinations, recommended readouts match well with GC-MS with less than 5.9% relative error. Moreover, this electrochemical sensor presented a promising method for assessing the safety of cyanides in Baijiu.

Effect of Oxycodone-Based Multimodal Analgesia on Visceral Pain After Major Laparoscopic Gastrointestinal Surgery: A Randomised, Double-Blind, Controlled Trial.

Purpose: Oxycodone is a potent µ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery. Methods: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1. Results: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups. Conclusion: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100052085).

Mechanistic studies of adsorption and ion exchange of Si(OH)4 molecules on the surface of scorodites.

Scorodites are commonly used for arsenic immobilization, and it is also the main component of arsenic bearing tailings. Alkali-activated geopolymers are commonly used to landfill arsenic-bearing minerals. However, there no previous studies have explored the interaction between geopolymer molecules and the surface of scorodite. In this paper, Si(OH)4 as a monomer molecule of geopolymer, the mechanism of adsorption and 'ion exchange' between Si(OH)4 molecule and the surface of scorodite during alkali-activation is studied. Results show that the Fe-terminated scorodite (010) surface has high stability. Si(OH)4 are more easily adsorbed on the hollow site of an Fe-terminated scorodite (010) surface, which is described as chemisorption. Compared with Si(OH)4, NaOH is easier to adsorb on an Fe-terminated scorodite (010) surface. The co-adsorption of NaOH and Si(OH)4 on the Fe-terminated scorodite (010) surface was studied, and also belongs to chemical adsorption. When the hydroxyl binds to the As atom, the adsorbed Si(OH)4 is more likely to undergo an 'ion exchange' reaction with the surface, and the reaction is barrierless. The intermediate As(OH)4 produced by the 'ion exchange' reaction can be deprotonated to form an arsenate molecule, which can occur spontaneously. This work reveals that the interaction mechanism of geopolymer molecules on surface of scorodite.

Lymph node targeting strategy using a hydrogel sustained-release system to load effector memory T cells improves the anti-tumor efficacy of anti-PD-1.

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: F127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.

Polyoxometalate-Intercalated Tremella-Like CoNi-LDH Nanocomposites for Electrocatalytic Nitrite-Ammonia Conversion.

The electrocatalytic reduction of NO2- (NO2RR) holds promise as a sustainable pathway to both promoting the development of emerging NH3 economies and allowing the closing of the NOx loop. Highly efficient electrocatalysts that could facilitate this complex six-electron transfer process are urgently desired. Herein, tremella-like CoNi-LDH intercalated by cyclic polyoxometalate (POM) anion P8W48 (P8W48/CoNi-LDH) prepared by a simple two-step hydrothermal-exfoliation assembly method is proposed as an effective electrocatalyst for NO2- to NH3 conversion. The introduction of POM with excellent redox ability tremendously increased the electrocatalytic performance of CoNi-LDH in the NO2RR process, causing P8W48/CoNi-LDH to exhibit large NH3 yield of 0.369 mmol h-1 mgcat-1 and exceptionally high Faradic efficiency of 97.0% at -1.3 V vs the Ag/AgCl reference electrode in 0.1 M phosphate buffer saline (PBS, pH = 7) containing 0.1 M NO2-. Furthermore, P8W48/CoNi-LDH demonstrated excellent durability during cyclic electrolysis. This work provides a new reference for the application of POM-based nanocomposites in the electrochemical reduction of NO2- to obtain value-added NH3.

Biomimetic MDSCs membrane coated black phosphorus nanosheets system for photothermal therapy/photodynamic therapy synergized chemotherapy of cancer.

Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

[Preparation of a macroporous anion exchange chromatographic medium by polyamine grafting and evaluation of its protein-adsorption behavior].

The macroporous anion exchange chromatographic medium (FastSep-PAA) was prepared through grafting polyallylamine (PAA) onto polyacrylate macroporous microspheres (FastSep-epoxy). The effects of the synthesis conditions, including the PAA concentration, reaction time, and reaction solution pH, on the ion exchange (IC) of the medium were investigated in detail. When the PAA concentration, reaction time, and reaction solution pH were increased, the IC of the medium increased, and optimal synthesis conditions were then selected in combination with changes of protein binding capacity. A scanning electron microscope was used to examine the surface morphology of the medium. The medium possessed high pore connectivity. Furthermore, the pore structure of the medium was preserved after the grafting of PAA onto the macroporous microspheres. This finding demonstrates that the density of the PAA ligands does not appear to have any discernible impact on the structure of the medium; that is, no difference in the structure of the medium is observed before and after the grafting of PAA onto the microspheres. The pore size and pore-size distribution of the medium before and after grafting were determined by mercury intrusion porosimetry and the nitrogen adsorption method to investigate the relationship between pore size (measured in the range of 300-1000 nm) and protein adsorption. When the pore size of the medium was increased, its protein binding capacity did not exhibit any substantial decrease. An increase in pore size may hasten the mass transfer of proteins within the medium. Among the media prepared, that with a pore size of 400 nm exhibited the highest dynamic-binding capacity (DBC: 70.3 g/L at 126 cm/h). The large specific surface area of the medium and its increased number of protein adsorption sites appeared to positively influence its DBC. When the flow rate was increased, the protein DBC decreased in media with original pore sizes of less than 700 nm. In the case of the medium with an original pore size of 1000 nm, the protein DBC was independent of the flow rate. The protein DBC decreased by 3.5% when the flow rate was increased from 126 to 628 cm/h. In addition, the protein DBC was maintained at 57.7 g/L even when the flow velocity was 628 cm/h. This finding reveals that the diffusion rate of protein molecules at this pore size is less restricted and that the prepared medium has excellent mass-transfer performance. These results confirm that the macroporous polymer anion exchange chromatographic medium developed in this study has great potential for the high-throughput separation of proteins.

WAV E3 ubiquitin ligases mediate degradation of IAA32/34 in the TMK1-mediated auxin signaling pathway during apical hook development.

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Narrative Review of Traditional Chinese Medicine in the Treatment of Postmenopausal Osteoporosis.

An increasing percentage of people in China are suffering from osteoporosis, particularly postmenopausal osteoporosis (PMOP), as the country rapidly evolves into an aging culture. Patients with osteoporosis are inclined to endure fractures, as well as deformities and impairments, which drastically decrease people's quality of life. The benefits of Traditional Chinese medicine (TCM) treatment have continued to become increasingly apparent as reports of adverse responses to Western medications increased. The main advantage of traditional Chinese medicine treatment is that pharmacological interactions may be employed to lessen adverse effects while increasing therapeutic efficacy. In addition, there are various exercise therapies created by medical doctors in the past generations, such as: Wuqinxi, Taijiquan, Baduanjin, Yijinjing, etc. Chinese medicine and exercise treatment for postmenopausal osteoporosis have garnered a lot of attention recently both domestically and internationally, and investigations demonstrate that these therapies have considerable therapeutic effects. The pathophysiology of postmenopausal osteoporosis, advancements of herbal therapy options, and exercise treatment options are all thoroughly addressed in this article.

[New advances in exposomics-analysis methods and research paradigms based on chromatography-mass spectrometry].

The occurrence and development of human diseases are influenced by both genetic and environmental factors. Research models that describe disease occurrence only from the perspective of genetics present certain limitations. In recent years, effects of environment factors on the occurrence and development of diseases have attracted extensive attentions. Exposomics focuses on the measurement of all exposure factors in an individual's life and how these factors are related to disease development. Exposomics provides new ideas to promote studies on the relationship between human health and environmental factors. Environmental exposures are characterized with different physical and chemical properties, as well as very low concentrations in vivo, which contribute great challenges in the comprehensive measurement of chemical residues in the human body. Chromatography-mass spectrometry-based technologies combine the high-efficiency separation ability of chromatography with the high resolution and sensitive detection characteristics of mass spectrometry; the combination of these techniques can achieve the high-coverage, high-throughput, and sensitive detection of environmental exposures, thus providing a powerful tool for measuring chemical exposures. Exposomics-analysis methods based on chromatography-mass spectrometry mainly include targeted quantitative analysis, suspect screening, and non-targeted screening. To explore the relationship between environmental exposure and the occurrence and development of diseases, researchers have developed research paradigms, including exposome wide association study, mixed-exposure study, exposomics and multi-omics (genome, transcriptome, proteome, metabolome)-association study, and so on. The emergence of these methods has brought about unprecedented developments in exposomics studies. In this manuscript, analytical methods based on chromatography-mass spectrometry, exposomics research paradigms, and their relevant prospects are reviewed.