A patent review of small molecular inhibitors targeting EGFR exon 20 insertion (Ex20ins) (2019-present).

Introduction: Mutations in epidermal growth factor receptor (EGFR) kinase domain consistently activate downstream signaling pathways, such as the PI3K/AKT/mTOR and RAS/RAF/MEK, thereby promoting tumor growth. Although the majority of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations are sensitive to existing EGFR tyrosine kinase inhibitors (EGFR-TKIs), there remains an unmet clinical need for effective therapies targeting EGFR Ex20ins mutations, making direct targeting EGFR Ex20ins mutations a promising therapeutic strategy.

Areas Covered: This review covers the progress of clinical studies targeting EGFR Ex20ins inhibitors and summarizes recent (1 January 2019 - 30 April 2024) patents disclosing EGFR Ex20ins inhibitors available in the Espacenet and CAS SciFinder databases.

Comparison of clinical outcomes between remodified Hanley procedure and modified Hanley procedure for high complex horseshoe fistula: a retrospective study.

Background: Treating high horseshoe anal fistula (HHAF) with the modified Halley procedure (MHP) often falls short when focusing solely on deep postanal space (DPAS) drainage. Our study underscores the significance of addressing deep posterior intersphincteric space (DPIS) drainage, prompting MHP modifications.

Methods: We studied consecutive patients with HHAF treated with either MHP or remodified-MHP (Re-MHP) at Ningbo Medical Center of Lihuili Hospital from January 2018 to December 2021.

Study on the Mechanism of Bifidobacterium animalis subsp. lactis F1-3-2 Regulating Bile Acid Metabolism Through TMA-TMAO Pathway to Improve Atherosclerosis.

Atherosclerosis is a major cause of cardiovascular disease (CVD). The trimethylamine (TMA)-trimethylamine N-oxide (TMAO) pathway is a key crossover pathway highly associated with diet, gut microbiome, and atherosclerosis. The Bifidobacterium animalis subsp.

Evaluating the Effectiveness of mRNA-1273.815 Against COVID-19 Hospitalization Among Adults Aged ≥ 18 Years in the United States.

Introduction: In September 2023 the Food and Drug Administration (FDA) approved an updated mRNA COVID-19 vaccine targeting the XBB.1.5 sublineage.

Green Carbon Dots/CaCO/Abamectin Colloidal Pesticide Formulation for Safer and More Effective Pest Management.

An ideal green leaf-deposited pesticide formulation should offer advantages such as good water dispersibility, strong foliar affinity, sustained or controlled release of active ingredients, photostability and rain-fastness, minimal nontarget toxicity, use of nontoxic organic solvents, and degradable adjuvants. In line with this objective, we present green preparation of a colloidal pesticide formulation using optimized lysine-derived carbon dots (LysCDs)-modified CaCO (LysCDs/CaCO) particles as the carrier and abamectin (Abm) as the active ingredient. The loading capacity of abamectin in this colloidal pesticide (LysCDs/CaCO/Abm) is 1.

Systemic lupus erythematosus is a risk factor for having multiple subtypes of cutaneous lupus erythematosus.

Background: Patients with cutaneous lupus erythematosus (CLE) can present with one or multiple different subtypes of CLE. There is limited understanding of the prevalence and associated risk factors for having multiple CLE subtype diagnoses.

Objective: This study characterized the frequency and risk factors for having multiple CLE subtypes.

Physician-Patient Communication about Novel Drugs and High-Risk Medical Devices.

Background: After a new drug or medical device is approved by the US Food and Drug Administration (FDA), physician-patient communication about benefits and risks is critical, including whether the product was approved through an expedited pathway based on limited evidence. In addition, physician reporting of drug- and device-related adverse events in real-world use is necessary to have a complete safety profile. We studied physician-reported communication and safety-reporting practices related to drugs and devices.

Voltage-Induced Bromide Redox Enables Capacity Restoration of Fast-Charging Batteries.

Fast-charging lithium-ion batteries (LIBs) are essential for electric vehicles (EVs) to compete with conventional gasoline ones in terms of charging viability, yet the aggressive capacity drop in fast-charging scenarios gives rise to concerns regarding durability and sustainability. Herein, it is clarified that for fast-charging batteries, the excessive lithium (Li) plating on graphite anode inevitably brings capacity fading, and the concurrent accumulation of LiO-dominant passivation species that form dead Li is the main reason for their poor rechargeability. To refresh the passivated graphite, a voltage-induced activation mechanism is developed to leverage bromide (Br/Br ) redox couple for LiO and isolated Li activation in situ.

Localized Morphological Modulation of Ultrathin Magnetic Nanosheets via a Strategically Designed Reduction Approach.

2D inorganic nanomaterials have attracted considerable research interest owing to their exceptional physical and chemical properties. Nonetheless, achieving precise control over the morphology of 2D nanomaterials presents a significant challenge, primarily due to their elevated surface energy and the stringent requirements for growth control. In this study, a designed reduction technique is employed to finely tune the morphology of 2D nanosheets, with iron salts serving as morphology-directing agents.

Two-dimensional Nanosheets by Liquid Metal Exfoliation.

Liquid exfoliation is a scalable and effective method for synthesizing 2D nanosheets (NSs) but often induces contamination and defects. Here, liquid metal gallium (Ga) is used to exfoliate bulk layered materials into 2D NSs at near room temperature, utilizing the liquid surface tension and Ga intercalation to disrupt Van der Waals (vdW) forces. In addition, the process can transform the 2H-phase of transition metal dichalcogenides into the 1T'-phase under ambient conditions.

Timely Application of Plasma Exchange to Correct Acute Pancreatitis Related to Serum Triglyceride Levels: A Report of 6 Cases and a Literature Review.

BACKGROUND Hypertriglyceridemia (HTG) is associated with circulating free fatty acids that can cause acute pancreatitis. Therapeutic plasma exchange (TPE) is a rapid and effective method of reducing triglyceride levels. This case series presents 6 cases of acute pancreatitis associated with hypertriglyceridemia with a rapid response to therapeutic plasma exchange.

Integrated machine learning reveals the role of tryptophan metabolism in clear cell renal cell carcinoma and its association with patient prognosis.

Background: Precision oncology's implementation in clinical practice faces significant constraints due to the inadequacies in tools for detailed patient stratification and personalized treatment methodologies. Dysregulated tryptophan metabolism has emerged as a crucial factor in tumor progression, encompassing immune suppression, proliferation, metastasis, and metabolic reprogramming. However, its precise role in clear cell renal cell carcinoma (ccRCC) remains unclear, and predictive models or signatures based on tryptophan metabolism are conspicuously lacking.

Effects of liraglutide on abdominal fat distribution and glucose metabolism in Chinese subjects with obesity.

Aims: To observe the effects of liraglutide on abdominal fat distribution in Chinese subjects with obesity in 12 weeks, and further to explore the correlation between abdominal fat content and glucose metabolism after monotherapy.

Methods: This study recruited 71 obese subjects. All the subjects have received liraglutide monotherapy (0.

Spatiotemporal differences induced changes in the structure and function of the gut microbiota in an endangered ungulate.

The composition and function of animal gut microbiota are shaped by various factors, among which diet is one of the major factors. Diet is affected by seasonal shifts and geographical differences, which in turn impact the host's nutritional levels. To adapt to these environmental changes, the gut microbiome often produces matching responses.

V-ATPase in cancer: mechanistic insights and therapeutic potentials.

Vacuolar-type H+-ATPase (V-ATPase) is a crucial proton pump that plays an essential role in maintaining intracellular pH homeostasis and a variety of physiological processes. This review provides an in-depth exploration of the structural components, functional mechanisms, and regulatory modes of V-ATPase in cancer cells. Comprising two main domains, V and V, V-ATPase drives the proton pump through ATP hydrolysis, sustaining the pH balance within the cell and organelles.

Clinical and functional characterization of a novel STUB1 mutation in a Chinese spinocerebellar ataxia 48 pedigree.

Background: Spinocerebellar ataxias (SCAs) encompass a wide spectrum of inherited neurodegenerative diseases, primarily characterized by pathological changes in the cerebellum, spinal cord, and brainstem degeneration. Autosomal dominant spinocerebellar ataxia type 48 (SCA48) is a newly identified subtype of SCA, marked by early-onset ataxia and cognitive impairment, and is associated with mutations in the STIP1 homology and U-box-containing protein 1 (STUB1) gene. The STUB1 gene encodes the protein CHIP (C-terminus of HSC70-interacting protein) which functions as E3 ubiquitin ligase and is crucial to the development of neural systems.

New insights into the combined effects of aflatoxin B1 and Eimeria ovinoidalis on uterine function by disrupting the gut-blood-reproductive axis in sheep.

Background: Sheep coccidiosis is an infectious parasitic disease that primarily causes diarrhea and growth retardation in young animals, significantly hindering the development of the sheep breeding industry. Cereal grains and animal feeds are frequently contaminated with mycotoxins worldwide, with aflatoxin B1 (AFB1) being the most common form. AFB1 poses a serious threat to gastrointestinal health upon ingestion and affects the function of parenteral organs, thus endangering livestock health.

Upper extremity function and disability recovery with vibration therapy after stroke: a systematic review and meta-analysis of RCTs.

Background: This study aimed to investigate the therapeutic effects of vibration therapy for improving upper extremity motor impairment, function, and disability recovery in people with stroke.

Design: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. PubMed, EMBASE, the Cochrane Library Database, Physiotherapy Evidence Database (PEDro), China Knowledge Resource Integrated Database, and Google Scholar were searched from inception to May 31, 2024.

A multicenter, randomized, parallel-controlled clinical trial protocol to evaluate the safety and efficacy of irreversible electroporation compared with radiofrequency ablation for the treatment of small hepatocellular carcinoma.

Background: At present, the main clinical application of local ablation therapy, such as radiofrequency ablation (RFA), is to heat the tissue to a certain temperature. However, high temperature will cause thermal damage. Irreversible electroporation (IRE) is a novel minimally invasive local ablation technology for tumors.

ABL1‒YAP1 axis in intestinal stem cell activated by deoxycholic acid contributes to hepatic steatosis.

Background: Yes-associated protein 1 (YAP1) regulates the survival, proliferation, and stemness of cells, and contributes to the development of metabolic dysfunction associated fatty liver disease (MAFLD). However, the regulatory role of intestinal YAP1 in MAFLD still remains unclear.

Methods: Terminal ileal specimens were used to compare intestinal YAP1 activation in patients with and without MAFLD.

Proteomic profiling reveals the significance of lipid metabolism in small cell lung cancer recurrence and metastasis.

Background: Small cell lung cancer (SCLC) is a lethal and recalcitrant malignancy with early metastases. However, the molecular and cellular mechanisms underlying its aggressive characteristics remain relatively elusive.

Methods: In this study, we conducted a comprehensive proteomic analysis of 90 primary tumors, 15 patient-matched lymph node metastatic tumors, and 15 brain metastatic tumors derived from a cohort of 105 SCLC patients.