Phase 2 study of serplulimab with the bevacizumab biosimilar HLX04 in the first-line treatment of advanced hepatocellular carcinoma.

Introduction: This study aimed to evaluate the safety and preliminary efficacy of serplulimab, a novel programmed death-1 inhibitor, with or without bevacizumab biosimilar HLX04 as first-line treatment in patients with advanced hepatocellular carcinoma.

Methods: This open-label, multicenter phase 2 study (clinicaltrials.gov identifier NCT03973112) was conducted in China and consisted of four treatment groups: group A (serplulimab 3 mg/kg plus HLX04 5 mg/kg, subsequent-line), group B (serplulimab 3 mg/kg plus HLX04 10 mg/kg, subsequent-line), group C (serplulimab 3 mg/kg, subsequent-line) and group D (serplulimab 3 mg/kg plus HLX04 10 mg/kg, first-line).

Quinazolinone nitriles and related metabolites from the deep-sea-derived fungus MCCC 3A00265.

Two new quinazolinone nitriles (1 and 2) and one new indole alkaloid (3), together with 13 known compounds, were isolated from the deep-sea-derived MCCC 3A00265. Their structures were determined by extensive spectroscopic analysis, with the absolute configurations established by comparing experimental and calculated electronic circular dichroism (ECD) and optical rotation (OR) data as well as biogenetic considerations. Viricyanoamides A and B (1 and 2) are the sole representatives of quinazolinones featuring a nitrile group, while solitumidine F (3) incorporates a rare pyrrolidinedione unit as an indole terpenoid.

Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 versus reference denosumab in healthy males: A randomized phase I study.

Denosumab is a human IgG2 monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL) for the treatment of osteoporosis and bone loss. HLX14 is a proposed biosimilar of denosumab. This randomized, parallel-group, two-part, phase I study aimed to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 with reference denosumab in Chinese healthy adult male participants.

Review and new insights into the catalytic structural domains of the Fe(ll) and 2-Oxoglutarate families.

Histone lysine demethylase (KDM), AlkB homolog (ALKBH), and Ten-Eleven Translocation (TET) proteins are members of the 2-Oxoglutarate (2OG) and ferrous iron-dependent oxygenases, each of which harbors a catalytic domain centered on a double-stranded β-helix whose topology restricts the regions directly involved in substrate binding. However, they have different catalytic functions, and the deeply structural biological reasons are not yet clear. In this review, the catalytic domain features of the three protein families are summarized from both sequence and structural perspectives.

The application of marine polysaccharides to antitumor nanocarriers.

Nanotechnology has revolutionized the diagnosis, monitoring and treatment of biomedical diseases, in which nanocarriers have greatly improved the targeting and bioavailability of antitumor drugs. The marine natural polysaccharides fucoidan, chitosan, alginate, carrageenan and porphyran have broad-spectrum bioactivities and unique physicochemical properties such as excellent non-toxicity, biocompatibility, biodegradability and reproducibility, which have placed them as a principal focus in the nanocarrier field. Nanocarriers based on different types of marine polysaccharides are distinctive in addressing antitumor therapeutic challenges such as targeting, environmental responsiveness, drug resistance, tissue toxicity, enhancing diagnostic imaging, overcoming the first-pass effect and innovative 3D binding.

An SNR Enhancement Method for Φ-OTDR Vibration Signals Based on the PCA-VSS-NLMS Algorithm.

To improve the signal-to-noise ratio (SNR) of vibration signals in a phase-sensitive optical time-domain reflectometer (Φ-OTDR) system, a principal component analysis variable step-size normalized least mean square (PCA-VSS-NLMS) denoising method was proposed in this study. First, the mathematical principle of the PCA-VSS-NLMS algorithm was constructed. This algorithm can adjust the input signal to achieve the best filter effect.

A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer.

Background: Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor.

Methods: This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813).

Designing a structure-function alphabet of helix based on reduced amino acid clusters.

Several simple secondary structures could form complex and diverse functional proteins, meaning that secondary structures may contain a lot of hidden information and are arranged according to certain principles, to carry enough information of functional specificity and diversity. However, these inner information and principles have not been understood systematically. In our study, we designed a structure-function alphabet of helix based on reduced amino acid clusters to describe the typical features of helices and delve into the information.

Anti-necroptosis and anti-ferroptosis compounds from the Deep-Sea-Derived fungus Aspergillus sp. MCCC 3A00392.

Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes.

Stimulus-Responsive Hydrogels as Drug Delivery Systems for Inflammation Targeted Therapy.

Deregulated inflammations induced by various factors are one of the most common diseases in people's daily life, while severe inflammation can even lead to death. Thus, the efficient treatment of inflammation has always been the hot topic in the research of medicine. In the past decades, as a potential biomaterial, stimuli-responsive hydrogels have been a focus of attention for the inflammation treatment due to their excellent biocompatibility and design flexibility.

Opportunities and challenges of fucoidan for tumors therapy.

The large-scale collections, screening and discovery of biologically active and pharmacologically significant marine-derived natural products have garnered tremendous attraction. Edible brown algae are rich in fucoidan. Importantly, fucoidan has been reported to inhibit carcinogenesis and metastasis mainly through the regulation of deregulated cell signaling pathways.

Chemical Constituents of the Deep-sea Gammarid Shrimp-Derived Fungus Penicillium citrinum XIA-16.

One new alkaloid, (S)-2-acetamido-4-(2-(methylamino)phenyl)-4-oxobutanoic acid (1), was isolated from the deep-sea-derived Penicillium citrinum XIA-16, together with 25 known compounds including ten polyketones (2-11), eight alkaloids (12-19), six steroids (20-25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra.

Fast Feature Extraction Method for Brillouin Scattering Spectrum of OPGW Optical Cable Based on BOTDR.

Brillouin optical time domain reflectometry (BOTDR) detects fiber temperature and strain data and represents one of the most critical ways of identifying abnormal conditions such as ice coverage and lightning strikes on optical fiber composite overhead ground wire (OPGW) cable. Existing BOTDR extracts brillouin frequency shift (BFS) features with cumulative averaging and curve fitting. BFS feature extraction is slow for long-distance measurements, making realizing real-time measurements on fiber optic cables challenging.

Isolation, Characterization, and Anti-Idiopathic Pulmonary Fibrosis Activity of a Fucoidan from .

Pulmonary fibrosis is a chronic, progressive, and fatal disease of the interstitial lung. There is currently a lack of efficient therapy to reverse the prognosis of patients. In this study, a fucoidan from was isolated, and its anti-idiopathic fibrosis activity was investigated both in vitro and in vivo.

Nanomedicine for the Detection and Treatment of Ocular Bacterial Infections.

Ocular bacterial infection is a prevalent cause of blindness worldwide, with substantial consequences for normal human life. Traditional treatments for ocular bacterial infections areless effective, necessitating the development of novel techniques to enable accurate diagnosis, precise drug delivery, and effective treatment alternatives. With the rapid advancement of nanoscience and biomedicine, increasing emphasis has been placed on multifunctional nanosystems to overcome the challenges posed by ocular bacterial infections.

Ferroptosis Inhibitory Compounds from the Deep-Sea-Derived Fungus sp. MCCC 3A00126.

Two new xanthones ( and ) were isolated from the deep-sea-derived fungus sp. MCCC 3A00126 along with 34 known compounds (-). The structures of the new compounds were established by spectroscopic data.

Comparing the pharmacokinetics, safety, and immunogenicity of HLX02 to US- and EU-approved trastuzumab in healthy Chinese male subjects: A Phase I, randomized, double-blind, parallel-group study.

Background: HLX02, the first China-manufactured trastuzumab biosimilar, is approved in Europe (EU) and China. This study evaluated bioequivalence between HLX02 and US-approved trastuzumab (US-trastuzumab).

Method: In this double-blind, parallel-group, Phase I study, healthy Chinese men were randomized (1:1:1) to receive a single 6 mg/kg dose of HLX02, reference US-trastuzumab, or reference EU-approved trastuzumab (EU-trastuzumab).

Heuristic Routing Algorithms for Time-Sensitive Networks in Smart Factories.

Over recent years, traditional manufacturing factories have been accelerating their transformation and upgrade toward smart factories, which are an important concept within Industry 4.0. As a key communication technology in the industrial internet architecture, time-sensitive networks (TSNs) can break through communication barriers between subsystems within smart factories and form a common network for various network flows.

Local charge transport at different interfaces in epoxy composites.

Charge transport in insulating composites is fundamental to designing high performance in electrical breakdown strength processes. A fundamental understanding of the charge transport at nanoscale in insulating composites remains elusive. Herein, we fabricate two types of interfaces in epoxy (EP) composites (AlO/EP and bubble/EP, respectively).

Hydroxysafflor Yellow A Alleviates Ischemic Stroke in Rats via HIF-1[Formula: see text], BNIP3, and Notch1-Mediated Inhibition of Autophagy.

Stroke has become a major cause of death and disability worldwide. The cellular recycling pathway autophagy has been implicated in ischemia-induced neuronal changes, but whether autophagy plays a beneficial or detrimental role is controversial. Hydroxysafflor Yellow A (HSYA), a popular herbal medicine, is an extract of Carthamus tinctorius and is used to treat ischemic stroke (IS) in China.