Customizable OpenGUS immunoassay: A homogeneous detection system using ß-glucuronidase switch and label-free antibody.

We developed a customizable OpenGUS immunoassay that enables rapid and sensitive detection of analytes without requiring antibody modification. This immunoassay employs label-free whole antibodies, an antibody-binding Z domain (ZD) derived from Staphylococcal protein A, and a ß-glucuronidase (GUS) switch mutant, allowing for easy replacement of antibodies to tailor the immunoassays for various targeted antigens. The working principle is that the OpenGUS probe, the fusion protein of ZD and a GUS switch, converts the antibody-antigen interaction into GUS activation in a one-pot reaction. To enhance the signal-to-background ratio of the immunoassay, a GUS switch mutant that exhibits reduced background activation was developed by screening several additional mutations at the diagonal interface residue H514. Moreover, we optimized the composition of the reaction buffer, including organic solvents, salt, and surfactant. Under optimal conditions, we customized OpenGUS immunoassays for Cry j 1, human C-reactive protein, and human lactoferrin, achieving around 10-20-fold maximum fluorescence (15 min) or colorimetric (2 h) responses with picomolar to low nanomolar level detection limit, simply by using commercially available IgGs. Additionally, the three analytes were successfully detected in complex matrices similar to those used in practical applications. We believe that this customizable OpenGUS immunoassay will pave the way for the prompt development of rapid and sensitive homogeneous immunoassays for point-of-care diagnostics, high-throughput testing, and onsite environmental assessments.

Patient-Reported Outcomes of Postoperative NSCLC Patients with or without Staged Chinese Herb Medicine Therapy during Adjuvant Chemotherapy (NALLC 2): A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION: The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).

Application of the mesh bridging technique in the excision of abdominal endometriosis lesions: Case report and literature review.

Abdominal wall scar endometriosis (AWE) is a rare endometriosis that usually occurs after gynecological or obstetric surgery and for which surgical resection is the standard treatment. For large tissue defects after resection, abdominal wall reconstruction is needed. Here, we describe a mesh bridging technique using biological and polypropylene meshes for abdominal wall reconstruction. A 34-year-old woman visited the center with complaints of low abdominal wall pain during menstruation for more than 5 years. Her surgical history included undergoing a cesarean section delivery twice. A mass measuring 6 cm × 5 cm × 3 cm was found above the symphysis pubis in the lower part of the abdominal incision. Endometriosis lesion was considered based on abdominal ultrasound and magnetic resonance imaging findings. After a multidisciplinary discussion that included surgical experts and gynecologists, the decision was made to perform abdominal endometrial focus excision plus abdominal wall reconstruction. Two kinds of mesh were skillfully used in the operation of this patient. Biological mesh was used close to the peritoneal side and covered with polypropylene mesh to reduce the stimulation by the polypropylene mesh of the peritoneum, enhance the strength of the biological mesh, and reduce the incidence of abdominal wall hernia. Our case demonstrates that accurate diagnosis of AWE followed by complete resection and reconstruction of the abdominal wall using a combination of biological and polypropylene mesh bridging can achieve good therapeutic results and patient satisfaction.

Biofilm formation on MgFe-LDH@quartz sand as novel wetland substrate under varied C/N ratios for BDE-47 removal.

Layered double hydroxide (LDH)-coated substrates could enhance the removal of various wastewater-born pollutants. However, research on biofilms attached to LDH-coatings and their synergistic purification effects on strongly hydrophobic persistent organic pollutants (POPs) remains limited. This study aims to investigate biofilm formation on MgFe-LDH@quartz sand and its effectiveness in removing tetrabromodiphenyl ether (BDE-47), an emerging halogenated POP in municipal wastewater. Under different C/N ratios (3, 5, and 10), BDE-47 removal rates ranged from 28.0% to 41.6% after 72 h. The optimal performance was achieved with LDH coating at C/N = 5, when substrate biofilm reached its highest extracelluar polymer substances (EPS) content, dehydrogenase activity and relative hydrophobicity. Moreover, distinct distribution patterns of EPS components' fluorescence peaks were observed in the LDH-coating treatment using three dimensional excitation-emission matrix (3D-EEM). While substrate adsorption was the primary mechanism for BDE-47 removal, accounting for 59.6%-83.4% of the total, biofilm adsorption and degradation contributed a relatively lower amount, ranging from 11.5% to 21.4%, and were more dependent on the C/N ratio. Notably, the maximum carrying capacity of protein predicted by the logistic growth model exhibited a strong positive correlation with the total BDE-47 removal rate (R2 = 0.82, p < 0.05), highlighting the importance of biofilm extracelluar proteins.

Migratory Connectivity of Zhejiang, with a Critical Stopover in East Asian-Australasian Flyway, Based on Recovery Data.

Understanding migratory routes is crucial for the conservation of birds and their habitats. Zhejiang is a crucial stopover and wintering area for birds in the East Asian-Australasian Flyway; however, detailed information on this area, and particularly on connections between coastal areas, is limited. By synthesizing ringed and recapture records from local bird-ringing projects and re-sighting community science data (208 records of 35 species), we established migratory connectivity between the Zhejiang coast and nine countries (i.e., Russia, Mongolia, the United States, Korea, Japan, Malaysia, Singapore, Thailand, and Australia), as well as eleven sites within China, and established its crucial role in this flyway. Stopover fidelity was verified by some species with high recapture frequency (seven species exceeded 1%) and species with duplicated re-sighted records (seven Black-faced Spoonbill, one Dalmatian Pelican, and two Spoon-billed Sandpiper individuals). We identified six areas-Hangzhou Bay, Aiwan Bay, Xuanmen National Park, Wenzhou Bay, the reclaimed area between the Ou and Feiyun Rivers, and the Wenzhou Jiangnan Reclamation Area-as crucial stopovers and wintering refuges for waterbirds. Notably, in Xuanmen National Park and the coastal regions along Wenzhou, there were many recovery records for flagship species, such as the Black-faced Spoonbill and Spoon-billed Sandpiper. There were several cases of the recovery of the same individual studied across the years. These findings indicate that these unprotected wetlands require particular attention. Broadly, our findings highlight the feasibility of integrating comprehensive ringing projects with citizen science data to formulate effective conservation strategies and underscore the critical importance of the Zhejiang Coast for migratory waterbirds, particularly those with high conservation concerns, emphasizing the need to mitigate the threats faced by these vulnerable populations.

Experimental quantum Byzantine agreement on a three-user quantum network with integrated photonics.

Quantum communication networks are crucial for both secure communication and cryptographic networked tasks. Building quantum communication networks in a scalable and cost-effective way is essential for their widespread adoption. Here, we establish a complete polarization entanglement-based fully connected network, which features an ultrabright integrated Bragg reflection waveguide quantum source, managed by an untrusted service provider, and a streamlined polarization analysis module, which requires only one single-photon detector for each user. We perform a continuously working quantum entanglement distribution and create correlated bit strings between users. Within the framework of one-time universal hashing, we provide the experimental implementation of source-independent quantum digital signatures using imperfect keys circumventing the necessity for private amplification. We further beat the 1/3 fault tolerance bound in the Byzantine agreement, achieving unconditional security without relying on sophisticated techniques. Our results offer an affordable and practical route for addressing consensus challenges within the emerging quantum network landscape.

Unraveling the Structure-Spectrum Relationship of Yeast Phenylalanine Transfer RNA: Insights from Theoretical Modeling of Infrared Spectroscopy.

Yeast phenylalanine tRNA (tRNAphe) is a paradigmatic model in structural biology. In this work, we combine molecular dynamics simulations and spectroscopy modeling to establish a direct link between its structure, conformational dynamics, and infrared (IR) spectra. Employing recently developed vibrational frequency maps and coupling models, we apply a mixed quantum/classical treatment of the line shape theory to simulate the IR spectra of tRNAphe in the 1600-1800 cm-1 region across its folded and unfolded conformations and under varying concentrations of Mg2+ ions. The predicted IR spectra of folded and unfolded tRNAphe are in good agreement with experimental measurements, validating our theoretical framework. We then elucidate how the characteristic L-shaped tertiary structure of the tRNA and its modulation in response to diverse chemical environments give rise to distinct IR absorption peaks and line shapes. These calculations effectively bridge IR spectroscopy experiments and atomistic molecular simulations, unraveling the molecular origins of the observed IR spectra of tRNAphe. This work presents a robust theoretical protocol for modeling the IR spectroscopy of nucleic acids, which will facilitate its application as a sensitive probe for detecting the fluctuating secondary and tertiary structures of these essential biological macromolecules.

Ginsenoside Rg3 Restores Mitochondrial Cardiolipin Homeostasis via GRB2 to Prevent Parkinson's Disease.

Regulating cardiolipin to maintain mitochondrial homeostasis is a promising strategy for addressing Parkinson's disease (PD). Through a comprehensive screening and validation process involving multiple models, ginsenoside Rg3 (Rg3) as a compound capable of enhancing cardiolipin levels is identified. This augmentation in cardiolipin levels fosters mitochondrial homeostasis by bolstering mitochondrial unfolded protein response, promoting mitophagy, and enhancing mitochondrial oxidative phosphorylation. Consequently, this cascade enhances the survival of tyrosine hydroxylase positive (TH+) dopaminergic neurons, leading to an amelioration in motor performance within PD mouse models. Using limited proteolysis-small-molecule mapping combined with molecular docking analysis, it has confirmed Growth Factor Receptor-Bound Protein 2 (GRB2) as a molecular target for Rg3. Furthermore, these investigations reveal that Rg3 facilitates the interaction between GRB2 and TRKA (Neurotrophic Tyrosine Kinase, Receptor, Type 1), thus promotes EVI1 (Ecotropic Virus Integration Site 1 Protein Homolog) phosphorylation by ERK, subsequently increases CRLS1 (Cardiolipin Synthase 1) gene expression and boosts cardiolipin synthesis. The absence of GRB2 or CRLS1 significantly attenuates the beneficial effects of Rg3 on PD symptoms. Finally, Tenofovir Disoproxil Fumarate (TDF) that also promotes the binding between GRB2 and TRKA is further identified. The identified compounds, Rg3 and TDF, exhibit promising potential for the prevention of PD by bolstering cardiolipin expression and reinstating mitochondrial homeostasis.

Synergy Between Dynamic Behavior of Hydrogen Defects and Non-Radiative Recombination in Metal-Halide Perovskites.

In organic-inorganic hybrid perovskite solar cells (PSCs), hydrogen defects introduce deep-level trap states, significantly influencing non-radiative recombination processes. Those defects are primarily observed in MA-PSCs rather than FA-PSCs. As a result, MA-PSCs demonstrated a lower efficiency of 23.6% compared to 26.1% of FA-PSCs. In this work, both hydrogen vacancy (VH -) and hydrogen interstitial (Hi -) defects in MAPbI3 bulk and on surfaces, respectively are investigated. i) Bulk VH - defects have dramatic impact on non-radiative recombination, with lifetime varying from 67 to 8 ns, depending on whether deprotonated MA0 are ion-bonded or not. ii) Surface H-defects exhibited an inherent self-healing mechanism through a chemical bond between MA0 and Pb2+, indicating a self-passivation effect. iii) Both VH - and Hi - defects can be mitigated by alkali cation passivation; while large cations are preferable for VH - passivation, given strong binding energy of cation/perovskite, as well as, weak band edge non-adiabatic couplings; and small cations are suited for Hi - passivation, considering the steric hindrance effect. The dual passivation strategy addressed diverse experimental outcomes, particularly in enhancing performance associated with cation selections. The dynamic connection between hydrogen defects and non-radiative recombination is elucidated, providing insights into hydrogen defect passivation essential for high-performance PSCs fabrication.

Circ_0079480 facilitates proliferation, migration and fibrosis of atrial fibroblasts in atrial fibrillation by sponing miR-338-3p to activate the THBS1/TGF-ß1/Smad3 signaling.

BACKGROUND: Atrial fibrosis is associated with the pathogenesis of atrial fibrillation (AF). This study aims to discuss the function of circ_0079480 in atrial fibrosis and its underlying mechanism. METHODS: In vitro and in vivo models of atrial fibrosis were established by using angiotensin II (Ang II) to treat human atrial fibroblasts (HAFs) and C57/B6J mice. qRT-PCR and western blot were used to examine the mRNA and protein expression levels. CCK-8, EdU, cell strach, and transwell assays were performed to determine the proliferation and migration of HAFs. Dual-luciferase reporter and RIP/RNA pull-down assays were explored to identify the interaction of miR-338-3p and circ_0079480/THBS1. HE and Masson's trichrome staining experiments were performed to analyze the histopathological change in mice atrial tissues. RESULTS: Circ_0079480 expression was increased in AF patients' atrial tissues and Ang II-treated HAFs. Silencing circ_0079480 inhibited cell proliferation and migration and reduced fibrosis-associated gene expression in Ang II-treated HAFs. Circ_0079480 could target miR-338-3p to repress its expression. MiR-338-3p inhibitor blocked the inhibitory effects of circ_0079480 knockdown on HAFs proliferation, migration, and fibrosis. Thrombospondin-1 (THBS1) was confirmed as a downstream target of miR-338-3p, and circ_0079480 could sponge miR-338-3p to upregulate THBS1 expression. Moreover, silencing THBS1 suppressed Ang II-induced proliferation, migration, and fibrosis in HAFs. More importantly, depletion of circ_0079480 inactivated the THBS1/TGF-ß1/Smad3 signaling by upregulating miR-338-3p. Mice experiments also confirmed the suppression of circ_0079480 knockdown on atrial fibrosis. CONCLUSION: Circ_0079480 acts as a sponge of miR-338-3p to upregulate THBS1 expression and activate the TGF-ß1/Smad3 signaling, finally promoting Ang II-induced atrial fibrosis.

Organolanthanide Single-Molecule Magnets with Heterocyclic Ligands.

Lanthanide (Ln) based mononuclear single-molecule magnets (SMMs) provide probably the finest ligand regulation model for magnetic property. Recently, the development of such SMMs has witnessed a fast transition from coordination to organometallic complexes because the latter provides a fertile, yet not fully excavated soil for the development of SMMs. Especially those SMMs with heterocyclic ligands have shown the potential to reach higher blocking temperature. In this minireview, we give an overview of the design principle of SMMs and highlight those "shining stars" of heterocyclic organolanthanide SMMs based on the ring sizes of ligands, analysing how the electronic structures of those ligands and the stiffness of subsequently formed molecules affect the dynamic magnetism of SMMs. Finally, we envisaged the future development of heterocyclic Ln-SMMs.

Large-Area Layered Membranes with Precisely Controlled Nano-Confined Channels.

Two-dimensional (2D) nanosheets-based membranes, which have controlled 2D nano-confined channels, are highly desirable for molecular/ionic sieving and confined reactions. However, it is still difficult to develop an efficient method to prepare large-area membranes with high stability, high orientation, and accurately adjustable interlayer spacing. Here, we present a strategy to produce metal ion cross-linked membranes with precisely controlled 2D nano-confined channels and high stability in different solutions using superspreading shear-flow-induced assembly strategy. For example, membranes based on graphene oxide (GO) exhibit interlayer spacing ranging from 8.0±0.1 Što 10.3±0.2 Å, with a precision of down to 1 Å. At the same time, the value of the orientation order parameter (f) of GO membranes is up to 0.95 and GO membranes exhibit superb stability in different solutions. The strategy we present, which can be generalized to the preparation of 2D nano-confined channels based on a variety of 2D materials, will expand the application scope and provide better performances of membranes.

Different Contributions of embB and ubiA Mutations to Variable Level of Ethambutol Resistance in Mycobacterium tuberculosis Isolates.

Objective: To explore the association between the variant mutations within embB and ubiA, and the degree of ethambutol (EMB) resistance of Mycobacterium tuberculosis (M. tuberculosis) isolates. Methods: A total of 146 M. tuberculosis isolates were used to determine the minimum inhibitory concentrations (MICs) of EMB with a 96-well microplate-based assay. The mutations within embB and ubiA among these isolates were identified with DNA sequencing. Moreover, a multivariate regression model and a computer model were established to assess the effects of mutations on EMB resistance. Results: Our data showed that overall 100 isolates exhibited 28 mutated patterns within the sequenced embB and ubiA. Statistical analysis indicated that embB mutations Met306Val, Met306Ile, Gly406Ala, and Gln497Arg, were strongly associated with EMB resistance. Of these mutations, Met306Val and Gln497Arg were significantly associated with high-level EMB resistance. Almost all multiple mutations occurred in high-level EMB-resistant isolates. Although the mutation within ubiA accompanied with embB mutation presented exclusively in EMB-resistant isolates, four single ubiA mutations (Ala39Glu, Ser173Ala, Trp175Cys, and Val283Leu) leading to protein instability were observed in EMB-susceptible isolates. Conclusion: This study highlighted the complexity of EMB resistance. Some individual mutations and multiple mutations within embB and ubiA contributed to the different levels of EMB resistance.

Pervaporation Dehydration Mechanism and Performance of High-Aluminum ZSM-5 Zeolite Membranes for Organic Solvents.

Membrane-based pervaporation (PV) for organic solvent dehydration is of great significance in the chemical and petrochemical industries. In this work, high-aluminum ZSM-5 zeolite membranes were synthesized by a fluoride-assisted secondary growth on α-alumina tubular supports using mordenite framework inverted (MFI) nanoseeds (~110 nm) and a template-free synthesis solution with a low Si/Al ratio of 10. Characterization by XRD, EDX, and SEM revealed that the prepared membrane was a pure-phase ZSM-5 zeolite membrane with a Si/Al ratio of 3.8 and a thickness of 2.8 µm. Subsequently, two categories of PV performance parameters (i.e., flux versus separation factor and permeance versus selectivity) were used to systematically examine the effects of operating conditions on the PV dehydration performance of different organic solvents (methanol, ethanol, n-propanol, and isopropanol), and their PV mechanisms were explored. Employing permeance and selectivity effectively disentangles the influence of operating conditions on PV performance, thereby elucidating the inherent contribution of membranes to separation performance. The results show that the mass transfer during PV dehydration of organic solvents was mainly dominated by the adsorption-diffusion mechanism. Furthermore, the diffusion of highly polar water and methanol molecules within membrane pores had a strong mutual slowing-down effect, resulting in significantly lower permeance than other binary systems. However, the mass transfer process for water/low-polar organic solvent (ethanol, n-propanol, and isopropanol) mixtures was mainly controlled by competitive adsorption caused by affinity differences. In addition, the high-aluminum ZSM-5 zeolite membrane exhibited superior PV dehydration performance for water/isopropanol mixtures.

The Reconstruction of Pt(001) Surface and the Shell-Like Reconstruction of the Vicinal Pt(001) Surfaces Revealed by Neural Network Potential.

In this work, a highly accurate neural network potential (NNP) is presented, named PtNNP, and the exploration of the reconstruction of the Pt(001) surface and its vicinal surfaces with it. Contrary to the most accepted understanding of the Pt(001) surface reconstruction, the study reveals that the main driving force behind Pt(001) quasi-hexagonal reconstruction is not the surface stress relaxation but the increased coordination number of the surface atoms resulting in stronger intralayer binding in the reconstructed surface layer. In agreement with experimental observations, the optimized supercell size of the reconstructed Pt(001) surface contains (5 × 20) unit cells. Surprisingly, the reconstruction of the vicinal Pt(001) surfaces leads to a smooth shell-like surface layer covering the whole surface and diminishing sharp step edges.

B cell lymphoma 6 promotes hepatocellular carcinoma progression by inhibiting tumor infiltrating CD4+T cell cytotoxicity through ESM1.

Immunotherapy exhibited potential effects for advanced hepatocellular carcinoma, unfortunately, the clinical benefits are often countered by cancer adaptive immune suppressive response. Uncovering the mechanism how cancer cells evade immune surveillance would help to develop new immunotherapy approaches and combination therapy. In this article, by analyzing the transcriptional factors which modulate the differentially expressed genes between T cell infiltration high group and low group, we identified oncoprotein B cell lymphoma 6 (BCL6) suppresses the infiltration and activation of tumor infiltrating T lymphocytes, thus correlated with poorer clinical outcome. By using antibody deletion experiment, we further demonstrated that CD4+T cells but not CD8+T cells are the main lymphocyte population suppressed by Bcl6 to promote HCC development. Mechanistically, BCL6 decreases cancer cell expression of pro-inflammatory cytokines and T lymphocyte chemokines such as IL6, IL1F6, and CCL5. Moreover, BCL6 upregulates Endothelial cell-specific molecule 1 (ESM1) to inhibit T lymphocyte recruitment and activation possibly through ICAM-1/LFA-1 signaling pathway. Our findings uncovered an unappreciated paracrine mechanism how cancer cell-derived BCL6 assists cancer cell immune evasion, and highlighted the role of CD4+T cells in HCC immune surveillance.

Spontaneous recovery in random hypergraphs.

In many real-world phenomena, such as the reconstruction of disaster areas after an earthquake or the stock market's recovery after an economic crisis, damaged networks are spontaneously active after receiving assistance. To reveal how the recovery process, the research of dynamic network recovery has become a hot topic in the field of network science. Previous studies on network recovery have been limited to simple networks with pairwise interactions. However, real-world systems are usually networks with higher-order interactions that are composed of multiple units. To better understand the recovery phenomenon on complex networks in the real world, we propose a novel spontaneous recovery model applied to hypergraphs. The model considers two types of recovery, internal recovery and fast recovery, where inactive nodes in the network can either recover internally with independent probabilities or receive sufficient resources from the hyperedge for fast recovery. We find that the number of active nodes in the system shows a phase change from continuous to discontinuous as the fast recovery condition is relaxed. Moreover, under the influence of higher-order interactions, increasing both average hyperedge cardinality and network heterogeneity contribute to increasing the network resilience. These findings help us understand the recovery mechanisms of complex networks and provide essential insights into designing highly resilient systems.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Unveiling heterogeneity and prognostic markers in ductal breast cancer through single-cell RNA-seq.

BACKGROUND: Breast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets. METHODS: Bioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes. RESULTS: The analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells. CONCLUSION: This study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

The Role of CD4+T Cells in Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has become the fourth leading cause of cancer-related deaths worldwide; annually, approximately 830,000 deaths related to liver cancer are diagnosed globally. Since early-stage HCC is clinically asymptomatic, traditional treatment modalities, including surgical ablation, are usually not applicable or result in recurrence. Immunotherapy, particularly immune checkpoint blockade (ICB), provides new hope for cancer therapy; however, immune evasion mechanisms counteract its efficiency. In addition to viral exposure and alcohol addiction, nonalcoholic steatohepatitis (NASH) has become a major cause of HCC. Owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance, NASH-associated HCC patients respond much less efficiently to ICB treatment than do patients with other etiologies. In addition, abnormal inflammation contributes to NASH progression and NASH-HCC transition, as well as to HCC immune evasion. Therefore, uncovering the detailed mechanism governing how NASH-associated immune cells contribute to NASH progression would benefit HCC prevention and improve HCC immunotherapy efficiency. In the following review, we focused our attention on summarizing the current knowledge of the role of CD4+T cells in NASH and HCC progression, and discuss potential therapeutic strategies involving the targeting of CD4+T cells for the treatment of NASH and HCC.