DDX3X mutation and Epstein-Barr virus cooperate to induce R-loop-dependent oncogenesis.

RNA helicase DDX3X is generally implicated in inflammasome activation and anti-viral responses. We characterize the common features of scattered DDX3X mutations in lymphoid cancers using molecular dynamics simulation and crystallization, thereby demonstrating their crucial role in Epstein-Barr virus (EBV) lytic gene-driven oncogenic processes. The DDX3X mutation is significantly related to impaired stimulator of interferon genes (STING)/ interferon regulatory factor 7 (IRF-7)/interferon (IFN)-α/β-mediated innate immunity, overexpression of EBV lytic gene BNLF2b, and increased formation of R-loops.

A phase 2 study of zanubrutinib in combination with rituximab and lenalidomide in de novo diffuse large B-cell lymphoma.

Older patients with diffuse large B cell lymphoma (DLBCL) present unfavorable genetic and microenvironmental alterations. In this phase 2 trial, we assessed the efficacy and safety of zanubrutinib in combination with rituximab and lenalidomide (ZR2) in patients with de novo DLBCL aged ≥75 years (NCT04460248). Forty patients were enrolled, and the primary endpoint was complete response rate, which was 65.

Case Report: Low-intensity transcranial focused ultrasound stimulation improves social interaction and stereotyped behavior in a boy with autism spectrum disorder.

Objectives: Presently, no biomedical therapies are available that specifically address the core symptoms of autism spectrum disorders. Given the evidence of cortical malfunction in ASD, low-intensity transcranial focused ultrasound stimulation has been discussed as a prospective therapeutic technique.

Methods: We describe the application of transcranial focused ultrasound to the left dorsolateral prefrontal cortex in a boy with ASD, which was applied for 30 minutes each consecutive weekday for four weeks (20 sessions in total).

Small-molecule Cathepsin K inhibitors: a medicinal chemistry perspective.

Cathepsin K (Cat K) is a member of the Cathepsin family and is found in a wide range of tissues. Cat K is involved in the terminal catabolism and recycling of endocytosed proteins, as well as specific cellular processes and a wide range of diseases. It is predominantly expressed in osteoclasts and has potent collagenase activity.

Genetic subtype-guided immunochemotherapy in relapsed and refractory diffuse large B cell lymphoma: a phase 2 investigator-initiated nonrandomized clinical trial (GUIDANCE-06).

Improving the outcome of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remained an unmet need. The aim of this single-center, phase 2 trial was to evaluate the efficacy and safety of genetic subtype-guided immunochemotherapy (R-ICE-X) in patients with R/R DLBCL: R-ICE-zanubrutinib for MCD-like and BN2-like, R-ICE-lenalidomide for N1-like and NOS, R-ICE-decitabine for TP53, R-ICE-chidamide for EZB-like, and R-ICE-tofacitinib for ST2-like subtype. Enrolled patients were treated with assigned regimens for three cycles, and then responders were treated with autologous hematopoietic stem cell transplantation (ASCT) or 3 cycles of R-ICE-X consolidation and lenalidomide maintenance.

An online detection method for municipal sludge moisture content based on ultrasonic transmission technology.

Accurate, real-time moisture content (MC) detection for municipal sludge is critical for optimizing dewatering and reducing treatment costs, which is difficult to implement due to its extremely complex physical and chemical properties. This study develops a novel online detection method, integrating ultrasonic transmission with a multivariate mixed regression (MMR) model, for non-destructive, high-precision online MC detection. Device geometry was optimized via COMSOL simulation, selecting a 40 kHz emission frequency and an 8 cm container distance, which together balance cavitation effects, energy dissipation, and cost-effectiveness.

Low-intensity focused ultrasound stimulation on the hippocampus improved CSDS-induced neuroinflammation through the Notch1 signaling pathway.

Exploring compensations for the limitations of current depression treatments holds significant social and clinical value. Low-intensity focused ultrasound (LIFU) is a promising emerging non-invasive therapy for the treatment of depression. Chronic social defeat stress (CSDS) is a validated rodent model of depression.

Characteristics and predictive model for diffuse large B-cell lymphoma with early chemoimmunotherapy failure.

Introduction: The outcomes of refractory or relapsed diffuse large B-cell lymphoma are generally poor, especially those relapsed or progressed within 12 months from diagnosis named as early chemoimmunotherapy failure (ECF), with a 2-year OS of 24.7%. Due to the dismal outcome, early recognition of ECF and developing targeted innovative treatments to improve patient prognosis are urgent.

Effects of Noise Reduction on the Physical and Mental State of Patients with Lumbar Disc Herniation in an Orthopedic Outpatient Clinic.

Unlabelled: Objective This study aimed to explore the effects of noise reduction on the physical and mental state of patients with lumbar disc herniation (LDH) in an orthopedic clinic.

Methods: A retrospective analysis was conducted on 120 patients with LDH who received conservative treatment in the orthopedic outpatient clinic of Tsinghua University Hospital from February 2022 to February 2023. The orthopedics department underwent noise reduction renovations in August 2022 and has implemented noise control management since then.

Baseline total lesion glycolysis identifies high-risk patients with immunosuppressive signatures in early-stage natural killer/T-cell lymphoma.

Background: The post-treatment Deauville scale (DS) and circulating Epstein-Barr virus (EBV)-DNA were used for prediction of long-term remission in natural killer/T-cell lymphoma (NKTCL). However, the baseline biomarkers still remain lacking for clinical application. Here, we hypothesized that 18F-FDG PET/CT, as a measure of total tumor burden, would be a baseline biomarker to identify high-risk NKTCL patients.

Extranodal diffuse large B-cell lymphoma: Clinical and molecular insights with survival outcomes from the multicenter EXPECT study.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin's lymphoma with distinct clinical and molecular heterogeneity. DLBCL that arises in extranodal organs is particularly linked to poor prognosis. This study aimed to determine the clinical and molecular characteristics of extranodal involvement (ENI) in DLBCL and assess the actual survival status of the patients.

Integration of gene mutations in risk prognostication for watch-and-wait follicular lymphoma patients initiating first-line treatment.

Follicular lymphoma (FL) patients with low tumor burden at diagnosis frequently undergo the watch-and-wait (W&W) strategy. The study aimed to facilitate risk assessment in predicting the time to lymphoma treatment (TLT) for W&W patients through an integrated analysis of clinical factors and genetic mutations. A retrospective study was conducted on 214 FL patients managed with W&W between 2016 and 2023.

Response-adapted zanubrutinib and tislelizumab as a potential strategy to enhance CD19 CAR T-cell therapy in relapsed/refractory large B-cell lymphoma: A retrospective observational study.

Background: CD19 chimeric antigen receptor (CAR) T-cell therapy is a potential treatment for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The combination of targeted therapeutic strategies, particularly bruton tyrosine kinase inhibitor zanubrutinib and programmed death-1 inhibitor tislelizumab, may improve clinical outcomes and modulate the tumour microenvironment (TME).

Methods: We studied patients with R/R LBCL who received response-adapted zanubrutinib plus tislelizumab upon CD19 CAR T-cell therapy between June 2021 and March 2023.

Molecular heterogeneity of CD30 peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre study.

Background: Peripheral T-cell lymphoma (PTCL) represents a highly heterogeneous group of non-Hodgkin's lymphomas, often with aggressive biological behaviour. CD30 serves as a pivotal surface antigen in PTCL, however, its biological functions and therapeutic potential warrant further investigation.

Methods: We analysed 415 de novo patients with PTCL including 314 in the training cohort and 101 in the validation cohort across 11 medical centres in China.

Dynamic change in Epstein-Barr virus DNA predicts prognosis in early stage natural killer/T-cell lymphoma with pegaspargase-based treatment: long-term follow-up and biomarker analysis from the NHL-004 multicenter randomized study.

The multi-center randomized phase 3 NHL-004 study compared etoposide, dexamethasone and pegaspargase (ESA) versus methotrexate, etoposide, dexamethasone and pegaspargase (MESA) regimen, combined with sandwiched radiotherapy, in newly diagnosed early-stage nasal natural killer/T-cell lymphoma (NKTCL). Here we report the long-term outcomes (median follow-up, 64 months) and biomarker analysis. 256 eligible patients aged 14-70 years were randomly assigned (1:1) to ESA or MESA arm.

Collaborative optimization of truck scheduling in container terminals using graph theory and DDQN.

The container terminal is a key node in global trade and logistics, where trucks connect quay cranes, storage yards, and vessels. Optimizing truck scheduling is crucial for enhancing port efficiency by addressing issues such as low truck utilization, excessive quay crane waiting times, and extended equipment completion times. This paper develops a container terminal simulation model based on graph theory, with the objective of minimizing the maximum completion time of terminal equipment.

A Review of the Treatments to Reduce Anti-Nutritional Factors and Fluidized Bed Drying of Pulses.

Pulses, rich in proteins, dietary fibers, and essential nutrients, play an important role in human nutrition, especially as alternatives to animal proteins. However, the presence of anti-nutritional factors (ANFs), such as trypsin inhibitors, chymotrypsin inhibitors, phytic acid, and tannins, can hinder nutrient absorption, reduce protein digestibility, and impair the overall nutritional value of these foods (pulses). This literature review critically examines fluidized bed drying (FBD) as a promising method for processing pulses, with a focus on the effectiveness of FBD in reducing ANFs while preserving protein quality.

Multifilm Mass Transfer and Reaction Rate Kinetics in a Newly Developed In Vitro Digestion System for Carbohydrate Digestion.

Multifilm mass transfer theory has been used in conjunction with developing a new in vitro starch digestion model and applied to assessing starch digestion kinetics. One significance of this research is that this in vitro model has similar dynamics, such as similar Reynolds numbers for both in vivo and in vitro systems. In the in vitro intestine model, when the flow rate changes from 5.

Mechanistic exploration of activated carbon synergistic solar drying through theoretical analysis coupled with experimental validation.

The rapid increase of sludge has brought significant environmental problems, the solar drying is an effective and economical method for sludge reduction. However, single solar drying has key issues such as low efficiency and long time. Thus, an interesting activated carbon synergistic solar (ACSS) technology which dried municipal sludge with was innovatively proposed in this paper.

Risk of acute renal failure associated with combined use of SGLT2 inhibitors and potentially nephrotoxic drugs: an epidemiological surveillance study based on the FDA adverse event reporting system (FAERS).

Background: Limited knowledge exists regarding nephrotoxic risks associated with the combination of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and potentially nephrotoxic drugs. This study evaluates acute renal failure (ARF) events linked to such combinations using data from the FDA Adverse Event Reporting System (FAERS).

Methods: Signal mining was performed by estimating reporting odds ratios (ROR), with validation through additive, multiplicative, and proportional reporting ratio (PRR) models.

Metabolic engineering of for high-level production of pneumocandin B.

Pneumocandin B (PB) is a lipohexapeptide synthesized by and serves as the precursor for the widely used antifungal drug caspofungin acetate (Cancidas®). However, the low titer of PB results in fermentation and purification costs during caspofungin production, limiting its widespread clinical application. Here, we engineered an efficient PB-producing strain of by systems metabolic engineering strategies, including multi-omics analysis and multilevel metabolic engineering.

Dual targeting PD-L1 and 4-1BB to overcome dendritic cell-mediated lenalidomide resistance in follicular lymphoma.

Immunomodulatory agent lenalidomide is effective in treating follicular lymphoma (FL). We conducted the first trial of immunotherapy rituximab plus lenalidomide in newly diagnosed FL in China (NCT03715309). One-hundred and fifteen patients were enrolled and treated with rituximab 375 mg/m intravenously on day 0 and lenalidomide 25 mg orally on day 1-10 for 6 cycles of induction treatment, as well as lenalidomide for 6 cycles and rituximab for 8 cycles of maintenance treatment.

Different Role of PET-CT Evaluation in Newly Diagnosed Follicular Lymphoma Upon Rituximab-Based Chemotherapy and Chemo-Free Immunotherapy.

Newly diagnosed follicular lymphoma (FL) patients usually received first-line rituximab-based immunochemotherapy (R-chemo). Recently, rituximab plus lenalidomide (R2) emerged as an alternative chemo-free immunotherapy. We performed a comparative analysis of positron emission tomography/computed tomography (PET/CT) in FL undergoing R-chemo or R2.

Innovative approaches in the discovery of terpenoid natural products.

As a class of natural compounds ubiquitous in nature, diverse terpenoids exhibit a broad spectrum of applications in human endeavors. The efficient discovery of novel terpenoids and the establishment of a terpene library for broad utilization represent pressing challenges in terpenoid natural product research. Various microbial platforms offer abundant precursors for terpene biosynthesis from diverse sources.