Journal of Zhejiang University SCIENCE B最新文献

Amid the rapid increase of the global population and the quest for sustainable agriculture, the need for enhanced rice breeding strategies has become increasingly pronounced, particularly in Heilongjiang, China's foremost rice-producing province, renowned for its premium temperate japonica rice. Here, we conducted an extensive genomic investigation of the elite rice cultivars developed in Heilongjiang Province. Using whole-genome re-sequencing of a total of 376 representative cultivars from Heilongjiang, of which 14 were developed by a single research group, we identified 4.9 million single nucleotide polymorphisms (SNPs) and 0.98 million insertions and deletions (InDels), offering a comprehensive perspective on genetic diversity and population structure. We classified the 376 rice cultivars into five subgroups based on their breeding years. Recently bred cultivars, assigned to subgroups HLJ-IV-1 and HLJ-IV-2, showed notable genetic differentiation. Through a selective sweep analysis, significant genomic variation in genes such as OsACBP5, Os4CL5, and GFR1 was pinpointed, reflecting a concerted effort in selecting for broad-spectrum disease resistance and enhanced tillering capacity. Furthermore, to identify the strengths and areas for improvement within those series, we conducted an exhaustive analysis of aromatic compounds and their corresponding genes OsODC and OsBadh2, as well as the advantageous long-grain gene OsGL3.1 haplotype within Hagengdao7. Additionally, strategies for reducing plant height through the introduction of the sd1 gene have been elucidated. With a commitment to expediting the development of superior rice cultivars, our discoveries are poised to raise the sensory attributes and nutritional profile of rice, thereby bolstering the resilience and sustainability of global food systems.

Hydrogels, owing to their porous network structure resembling the extracellular matrix (ECM), have become essential scaffold materials in the field of cartilage tissue engineering. Among them, gelatin methacrylate (GelMA) hydrogels are widely used in bioink development due to their excellent biocompatibility, biodegradability, and tunable photo-crosslinking properties. However, the high biocompatibility of pure GelMA often comes at the cost of mechanical strength, limiting its applicability in cartilage regeneration. To overcome this trade-off, this study developed composite bioinks based on GelMA, silk fibroin (SF), and polyethylene oxide (PEO) for fabricating porous hydrogel scaffolds, which were then systematically characterized in terms of morphology, porosity, hydrophilicity, mechanical strength, rheological behavior, printability, and cytocompatibility. In this design, PEO serves as a porogen to generate highly porous structures (porosity up to 88%), while SF compensates for the mechanical loss caused by PEO, enabling the scaffold to retain a compression strength of up to 29.10 kPa. Among the tested formulations, the 10% GelMA/1% SF/1.5% PEO (1%=0.01 g/mL) bioink exhibited excellent printability, mechanical integrity, and cytocompatibility, and it supported a robust deposition of collagen II and aggrecan by chondrocytes after printing. This work provides a versatile strategy for balancing the biocompatibility and mechanical robustness in bioinks, offering a promising platform for next-generation cartilage tissue engineering scaffolds.

Poly(ADP-ribose) polymerase (PARP) is a family of proteins that play a crucial role in diverse cellular processes, including DNA repair, cell death, and changes in chromatin structure. PARP inhibitors (PARPi) have been recognized as notable agents in the realm of anticancer therapeutics owing to their capacity to specifically impact DNA repair pathways, thereby inducing targeted death of cancerous cells, particularly in cancers with homologous recombination deficiency (HRD). These inhibitors have been approved for the treatment of several cancers, such as ovarian, breast, and pancreatic cancers. Despite their promising therapeutic attributes, developing resistance to PARPi presents a formidable obstacle, curtailing their overall efficacy. This article presents a comprehensive description of the potential mechanisms related to PARPi resistance, an in-depth study of potential strategies to overcome resistance, and an assessment of the therapeutic potential of the PARPi in combination with alternative therapies.

Acute respiratory distress syndrome (ARDS) is a form of progressive hypoxemia that can be brought on by a variety of cardiorespiratory or systemic disorders, such as coronavirus disease 2019 (COVID-19). The binding of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus spike protein to the cell membrane is mediated through its binding to angiotensin-converting enzyme 2 (ACE2) receptors, resulting in viral entry, replication, and induction of a signaling cascade inducing pro-inflammatory responses that are linked to a higher mortality rate and the progression of ARDS, leading to multi-organ failure in these patients. We aimed to analyze the relationships between circulating gene expression levels of ACE2, Toll-like receptor 4 (TLR4), and interleukin-17 (IL-17) and the clinical severity of COVID-19, as well as the associated pathogenic conditions, in hospitalized patients. Sixty COVID-19 patients (34 mild/moderate COVID-19 and 26 COVID-19 with severe ARDS manifestation) and 60 healthy controls were included. The patient group was also subdivided according to outcomes into 32 recoveries and 28 deaths. ACE2, TLR4, and IL-17 levels were assessed by quantitative polymerase chain reaction (qPCR) in addition to all routine baseline laboratory investigations, including complete blood count (CBC) with differential analysis and the levels of C-reactive protein (CRP), ferritin, and d-dimer. ACE2, TLR4, and IL-17 serum expression levels were significantly higher in the COVID-19 group and subgroups and were correlated with different laboratory and clinical parameters. The serum expression levels of ACE2, TLR4, and IL-17 were accurate in differentiating between the patient groups and controls, with 86.7%, 91.7%, and 95.0% sensitivity and 96.7%, 98.3%, and 98.3% specificity, respectively, and correlated with more severe disease courses in COVID-19 patients. Higher levels are associated with overwhelmingly distressing outcomes. Our results allow us to conclude that increased circulating gene expression levels of ACE2, TLR4, and IL-17 are important in assessing the severity of COVID-19. Consequently, targeting these biomarkers may offer additional therapeutic options for COVID-19 patients in the future.

Macrophages are sensitive cells to various external mechanical forces in the environment, such as stretch, shear, and pressure. Mechanical forces can be recognized by mechanical signal receptors on the cell surface, such as cell adhesion molecules and ion channels, and transformed into intracellular biological signals, in turn activating different signaling pathways and thereby regulating the phagocytosis, migration, and polarization of macrophages. The phenomenon in which macrophages transform into different activated phenotypes and perform different functions under varying environmental stimuli is also known as macrophage polarization. In this review, we discuss the roles of mechanically sensitive integrins and ion channels in the mechanical signal sensing of macrophages. We expound on several downstream signaling pathways closely related to integrins and ion channels, such as the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) pathways, which have made good research progress. In addition, we summarize some in vitro experiments on the regulation of macrophage polarization by external mechanical forces, some current cell models for macrophages in vitro, and some commonly used force application devices, with the aim to provide convenience for future in vitro research on macrophages. This paper offers a deep understanding of the mechanical sensitivity and conduction mechanisms of macrophages, which can provide new ideas for the treatment of human diseases.

Bone-related diseases, including osteoporosis (OP), osteoarthritis (OA), rheumatoid arthritis (RA), fracture, and periodontitis, significantly impact human health. Succinate, primarily known as a metabolic intermediate in the tricarboxylic acid (TCA) cycle, has emerged as a regulator of cellular functions beyond its metabolic role. Under stress, succinate accumulates in mitochondria and acts as a signaling molecule, modulating cellular processes. Notably, succinate activates angiogenesis and inflammation by stabilizing hypoxia-inducible factor-1α (HIF-1α). Moreover, it influences various pathophysiological processes by interacting with the succinate receptor 1 (SUCNR1), thereby impacting immune response, inflammation, cancer metastasis, and bone homeostasis. The multifaceted roles of succinate as a signaling molecule vary depending on its cellular location and concentration. Recent metabolomic analyses have revealed elevated succinate levels in bone-related diseases, indicating its potential association with these conditions. The objective of this review is to elucidate the impacts of succinate on different bone-related diseases and to discuss potential therapeutic targets and drug molecules based on its mechanisms of action.

Protein interacting with C kinase 1 (PICK1) interacts with a variety of membrane proteins and receptors involved in nervous system diseases and multiple cancers. However, the role of PICK1 in gastric cancer remains unclear. In the present work, we explored the expression and interactions of PICK1 with Toll-like receptor 4 (TLR4) in gastric cancer. Clinical data analysis showed that PICK1 expression decreases and is predictive of worse outcomes in patients with gastric cancer. High PICK1 levels attenuate the proliferation and migration of gastric cancer cells, which is dependent on the TLR4/myeloid differentiation primary response 88 (MyD88) signaling pathway. Furthermore, in vitro experiments demonstrated that PICK1 affects the trafficking and degradation of TLR4 and promotes TLR4 degradation via autophagy in gastric cancer cells. Molecular dynamics simulations highlighted the binding strength and stability of the TLR4-PICK1 complex. Our study provides new insights into the cellular and pathological functions of PICK1 in gastric cancer.

Excessive ammonia nitrogen has been demonstrated to cause a serious hazard to water environments. Bacteria performing simultaneous nitrification and denitrification (SND) can be effective biological instruments to remove ammonia nitrogen completely from effluents. For the first time, Pseudomonas oleovorans QS-7 with SND function, isolated from the biogas treatment system of a pig farm, was found to efficiently remove ammonia nitrogen. Through the determination of key enzymes and functional genes related to the nitrogen metabolism of strain QS-7, combined with nitrogen balance measurements of the nitrogen metabolic process, it was speculated that the SND pathway of the novel strain is N H 4+ →NH₂OH→ N O 2- → N O 3- → N O 2- →NO→N₂O→N₂. QS-7 exhibited 98.6% ammonia nitrogen removal and a maximum ammonia degradation rate of 9.2 mg/(L·h) at 18 h in 100 mg/L ammonia nitrogen solution. This strain also has a certain capacity to remove nitrate and nitrite nitrogen; the maximum removal efficiencies were 54.22% and 73.93%, respectively, in systems with 100 mg/L of nitrate or nitrite nitrogen as the sole nitrogen source. Nitrogen metabolic balance analysis for QS-7, using ammonia (100 mg/L) as the sole nitrogen source, demonstrated that assimilation (56.1%) is the main mode of nitrogen removal, followed by conversion to N₂ (43.6%). Meanwhile, N O 2- was not detected, and almost no NO_x was produced, which indicates that the nitrogen removal process of QS-7 is environmentally friendly. The optimal environmental conditions for QS-7 were found to be sodium citrate as the carbon source, C/N=10, pH=7.0, 150 r/min, and 30 ℃. The above results indicate that QS-7 may provide a material and conceptual basis for the advancement of SND technology.

The abnormal accumulation of methylmalonic acid (MMA), the leading cause of methylmalonic acidemia, can cause irreversible damage to the brain, kidney, and cardiovascular system. In addition, the accumulation of MMA in the blood has recently been associated with the occurrence of cancer, restricted bodily movement, and growth retardation. In this review, recent studies on the relationship between the metabolic abnormality of MMA and disease occurrence were summarized, concerning the brain, kidney, cardiovascular system, cancer, and skeletal muscles. It provides a theoretical basis and reference for further research and the treatment of MMA-related pathophysiological changes.

Oral squamous cell carcinoma (OSCC) poses significant challenges in terms of diagnosis and treatment, with high rates of morbidity and mortality. Emerging evidence highlights the critical involvement of Wingless/Int-1 (Wnt) ligands and receptors in OSCC pathogenesis. Dysregulated Wnt signaling pathways contribute to tumor initiation, progression, and therapy resistance by promoting cellular proliferation, epithelial‒mesenchymal transition (EMT), and the maintenance of cancer stem cells (CSCs). Targeting Wnt signaling presents a promising therapeutic avenue, yet its complex interplay with other signaling pathways requires a deeper understanding to implement effective intervention. This study sheds light on the current knowledge of the roles of Wnt ligands and receptors in OSCC, emphasizing their potential as diagnostic biomarkers and therapeutic targets. Future research directions involve elucidating context-specific Wnt signaling dynamics and exploring combination therapies to improve clinical outcomes for OSCC patients.