Imidazole functionalized photo-crosslinked aliphatic polycarbonate drug-eluting coatings on zinc alloys for osteogenesis, angiogenesis, and bacteriostasis in bone regeneration.

Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still hindered by challenges including excessive release of zinc ions (Zn2+), particularly in the early stage of implantation, and absence of bio-functions related to complex bone repair processes. Herein, a biodegradable aliphatic polycarbonate drug-eluting coating was fabricated on zinc-lithium (Zn-Li) alloys to inhibit Zn2+ release and enhance the osteogenesis, angiogenesis, and bacteriostasis of Zn alloys. Specifically, the photo-curable aliphatic polycarbonates were co-assembled with simvastatin and deposited onto Zn alloys to produce a drug-loaded coating, which was crosslinked by subsequent UV light irradiation. During the 60 days long-term immersion test, the coating showed distinguished stable drug release and Zn2+ release inhibition properties. Benefiting from the regulated release of Zn2+ and simvastatin, the coating facilitated the adhesion, proliferation, and differentiation of MC3T3-E1 cells, as well as the migration and tube formation of EA.hy926 cells. Astonishingly, the coating also showed remarkable antibacterial properties against both S. aureus and E. coli. The in vivo rabbit critical-size femur bone defects model demonstrated that the drug-eluting coating could efficiently promote new bone formation and the expression of platelet endothelial cell adhesion molecule-1 (CD31) and osteocalcin (OCN). The enhancement of osteogenesis, angiogenesis, and bacteriostasis is achieved by precisely controlling of the released Zn2+ at an appropriate level, as well as the stable release profile of simvastatin. This tailored aliphatic polycarbonate drug-eluting coating provides significant potential for clinical applications of Zn alloys implants.

[Clinical effect of acupuncture combined with medication on diabetic peripheral neuropathy and its influence on serum lipid metabolism].

OBJECTIVE: To observe the clinical effect on diabetic peripheral neuropathy (DPN) treated with acupuncture combined with medication and explore its effect mechanism. METHODS: Sixty-two patients of DPN were randomly divided into a combined therapy group (31 cases) and a medication group (31 cases, 2 cases dropped out); besides, 20 healthy subjects were recruited as a normal group. On the base of routine intervention, in the medication group, thioctic acid capsules were administrated orally, 0.2 g each time, 3 times a day. In the combined therapy group, besides the medication as the medication group, acupuncture was performed on bilateral Quchi (LI 11), Waiguan (TE 5), Hegu (LI 4), Tianshu (ST 25), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) and the needles were retained for 30 min, acupuncture was delivered once daily, 6 times a week. The duration of treatment was 4 weeks in the two groups. The score of Toronto clinical scoring system (TCSS), the nerve conduction velocity of median nerve (MN) and common peroneal nerve (CPN) were observed before and after treatment in the two intervention groups; and the serum lipid metabolism was detected before and after treatment in the two intervention groups and the normal group. RESULTS: Compared with that before treatment, the scores of TCSS were reduced in the combined therapy group and the medication group (P<0.05) after treatment, and the score decrease in the combined therapy group was larger than that of the medication group (P<0.001). The motor nerve conduction velocity and the sensory nerve conductive velocity of MN and CPN after treatment all increased in the combined therapy group and the medication group compared with those before treatment (P<0.05), and the improvements in the combined therapy group were larger than those of the medication group (P<0.001). Before treatment DPN patients had 365 differential lipid metabolites, including sphingosine (SPH, d18:0), involved in the inositol phosphate metabolism, compared with the subjects of the normal group. There were 103 differential lipid metabolites in the medication group before and after treatment, including lysophosphatidyl ethanolamine (LPE, 18:1/0:0), participated in glycerophospholipid metabolism. In the combined therapy group, before and after treatment, there were 99 differential lipid metabolites, including lysophosphatidylcholine (LPC, 18:0/0:0), participated in the neuroactive ligand-receptor interaction. Acupuncture greatly affected 50 lipid metabolites such as lysophosphatidic acid (LPA, 0:0/22:6), LPA(0:0/18:2) and LPC(O-18:0), which was mainly involved in glycerophospholipid metabolism. CONCLUSION: Acupuncture combined with medication ameliorates the symptoms and the nerve conduction velocity in DPN patients, which may be related to the regulation of serum lipid metabolism.

Integrated phenotypic, transcriptomics and metabolomics: growth status and metabolite accumulation pattern of medicinal materials at different harvest periods of Astragalus Membranaceus Mongholicus.

BACKGROUND: Astragalus membranaceus var. mongholicus (Astragalus), acknowledged as a pivotal "One Root of Medicine and Food", boasts dual applications in both culinary and medicinal domains. The growth and metabolite accumulation of medicinal roots during the harvest period is intricately regulated by a transcriptional regulatory network. One key challenge is to accurately pinpoint the harvest date during the transition from conventional yield content of medicinal materials to high and to identify the core regulators governing such a critical transition. To solve this problem, we performed a correlation analysis of phenotypic, transcriptome, and metabolome dynamics during the harvesting of Astragalus roots. RESULTS: First, our analysis identified stage-specific expression patterns for a significant proportion of the Astragalus root genes and unraveled the chronology of events that happen at the early and later stages of root harvest. Then, the results showed that different root developmental stages can be depicted by co-expressed genes of Astragalus. Moreover, we identified the key components and transcriptional regulation processes that determine root development during harvest. Furthermore, through correlating phenotypes, transcriptomes, and metabolomes at different harvesting periods, period D (Nov.6) was identified as the critical period of yield and flavonoid content increase, which is consistent with morphological and metabolic changes. In particular, we identified a flavonoid biosynthesis metabolite, isoliquiritigenin, as a core regulator of the synthesis of associated secondary metabolites in Astragalus. Further analyses and experiments showed that HMGCR, 4CL, CHS, and SQLE, along with its associated differentially expressed genes, induced conversion of metabolism processes, including the biosynthesis of isoflavones and triterpenoid saponins substances, thus leading to the transition to higher medicinal materials yield and active ingredient content. CONCLUSIONS: The findings of this work will clarify the differences in the biosynthetic mechanism of astragaloside IV and calycosin 7-O-ß-D-glucopyranoside accumulation between the four harvesting periods, which will guide the harvesting and production of Astragalus.

Xuebijing injection and its bioactive components alleviate nephrotic syndrome by inhibiting podocyte inflammatory injury.

Xuebijing injection (XBJ) is widely used to treat nephrotic syndrome (NS) in clinic, but its bioactive components and therapeutic mechanism are still unclear. In this study, the bioactive components of XBJ were determined by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). The therapeutic effect of XBJ on NS was evaluated in BALB/c mice induced by adriamycin (ADR, 10 mg/kg) via a single tail vein. The protective effect of XBJ and its bioactive components on podocytes was demonstrated using mouse podocytes (MPC-5) induced by lipopolysaccharide (LPS, 4 µg/mL). The results show that 33 components of XBJ were identified. Furthermore, 12 bioactive components were detected in blood, including protocatechuic acid, salvianolic acid C, benzoyloxypaeoniflorin, danshensu, salvianolic acid A, salvianolic acid B, catechin, caffeic acid, galloylpaeoniflorin, oxypaeoniflorin, hydroxysafflor yellow A, rosmarinic acid. The relative content (%) of the bioactive components were 59.32, 16.01, 9.97, 9.73, 8.72, 8.31, 7.92, 6.54, 1.54, 1.30, 0.68 and 0.59 in this order. After XBJ treatment, the renal function, hyperlipidemia and renal pathological damage were improved in NS model mice. Moreover, the levels of nephrin and desmin which are functional proteins in podocytes were reversed, and the levels of pro-inflammatory factors were reduced by XBJ. Interestingly, protocatechuic acid and salvianolic acid C also showed good protective effects on podocyte function and reduced the level of inflammation in LPS-induced MPC-5. The study is the first time to elucidate the bioactive components of XBJ and its potential therapeutic mechanism for treating NS by protecting podocyte function.

KLF4 suppresses anticancer effects of brusatol via transcriptional upregulating NCK2 expression in melanoma.

Brusatol (Bru), a main extract from traditional Chinese medicine Brucea javanica, has been reported to exist antitumor effect in many tumors including melanoma. However, the underlying mechanism in its anti-melanoma effect still need further exploration. Here, we reported that the protein expression of KLF4 in melanoma cells were significantly downregulated in response to brusatol treatment. Overexpression of KLF4 suppressed brusatol-induced melanoma cell apoptosis; while knockdown of KLF4 enhanced antitumor effects of brusatol on melanoma cells not only in vitro but also in vivo. Further studies on the mechanism revealed that KLF4 bound to the promoter of NCK2 directly and facilitated NCK2 transcription, which suppressed the antitumor effect of brusatol on melanoma. Furthermore, our findings showed that miR-150-3p was dramatically upregulated under brusatol treatment which resulted in the downregulation of KLF4. Our results suggested that the miR-150-3p/KLF4/NCK2 axis might play an important role in the antitumour effects of brusatol in melanoma.

Effects of Glutathione S-Transferases (GSTM1, GSTT1 and GSTP1) gene variants in combination with smoking or drinking on cancers: A meta-analysis.

BACKGROUND: This meta-analysis aimed to systematically summarize the association between cancer risks and glutathione s-transferases (GSTs) among smokers and drinkers. METHODS: Literature was searched through PubMed, Web of Science, CNKI, and WANFANG published from 2001 to 2022. Stata was used with fixed-effect model or random-effect model to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Sensitivity and heterogeneity calculations were performed, and publication bias was analyzed by Begg and Egger's test. Regression analysis was performed on the correlated variables about heterogeneity, and the false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) were calculated to assess the confidence of a statistically significant association. RESULTS: A total of 85 studies were eligible for GSTs and cancer with smoking status (19,604 cases and 23,710 controls), including 14 articles referring to drinking status (4409 cases and 5645 controls). GSTM1-null had significant associations with cancer risks (for smokers: OR = 1.347, 95% CI: 1.196-1.516, P < .001; for nonsmokers: OR = 1.423, 95% CI: 1.270-1.594, P < .001; for drinkers: OR = 1.748, 95% CI: 1.093-2.797, P = .02). GSTT1-null had significant associations with cancer risks (for smokers: OR = 1.356, 95% CI: 1.114-1.651, P = .002; for nonsmokers: OR = 1.103, 95% CI: 1.011-1.204, P = .028; for drinkers: OR = 1.423, 95% CI: 1.042-1.942, P = .026; for nondrinkers: OR = 1.458, 95% CI: 1.014-2.098, P = .042). Negative associations were found between GSTP1rs1695(AG + GG/AA) and cancer risks among nondrinkers (OR = 0.840, 95% CI: 0.711-0.985, P = .032). CONCLUSIONS: GSTM1-null and GSTT1-null might be related cancers in combination with smoking or drinking, and GSTP1rs1695 might be associated with cancers among drinkers.

NUCB2 inhibition antagonizes osteosarcoma progression and promotes anti-tumor immunity through inactivating NUCKS1/CXCL8 axis.

The oncogenic properties of Nucleobindin2 (NUCB2) have been observed in various cancer types. Nevertheless, the precise understanding of the biological functions and regulatory mechanisms of NUCB2 in osteosarcoma remains limited. This investigation reported that NUCB2 was significantly increased upon glucose deprivation-induced metabolic stress. Elevated NUCB2 suppressed glucose deprivation-induced cell death and reactive oxygen species (ROS) increase. Depletion of NUCB2 resulted in a reduction in osteosarcoma cell proliferation as well as metastatic potential in vitro and in vivo. Mechanically, NUCB2 ablation suppressed C-X-C Motif Chemokine Ligand 8 (CXCL8) expression which then reduced programmed cell death 1 ligand 1 (PD-L1) expression and stimulated anti-tumor immunity mediated through cytotoxic T cells. Importantly, a combination of NUCB2 depletion with anti-PD-L1 treatment improved anti-tumor T-cell immunity in vivo. Moreover, we further demonstrated that NUCB2 interacted with NUCKS1 to inhibit its degradation, which is responsible for the transcriptional regulation of CXCL8 expression. Altogether, the outcome emphasizes the function of NUCB2 in osteosarcoma and indicates that NUCB2 elevates osteosarcoma progression and immunosuppressive microenvironment through the NUCKS1/CXCL8 pathway.

HOXB9 promotes osteosarcoma cell survival and malignancy under glucose starvation via upregulating SPP1 expression.

Homeobox B9 (HOXB9) has been shown to play a critical role in several tumors. However, the precise biological mechanisms and functions of HOXB9 in osteosarcoma remain largely unknown. In this study, we found that HOXB9 was increased upon glucose starvation. Elevated HOXB9 suppressed osteosarcoma cell death and supported cell growth and migration under glucose starvation. Further mechanistic studies demonstrated that HOXB9 directly bound to the promoter of secreted phosphoprotein 1 (SPP1) and transcriptionally upregulated SPP1 expression which then led cell death decrease and cell growth increase under glucose deprivation environment. Clinically, HOXB9 was significantly upregulated in osteosarcoma compared with normal tissues and increase of HOXB9 expression was positively associated with the elevation of SPP1 in osteosarcoma. Overall, our study illustrates that HOXB9 contributes to malignancy in osteosarcoma and inhibits cell death through transcriptional upregulating SPP1 under glucose starvation.

Machine learning and genetic algorithm-guided directed evolution for the development of antimicrobial peptides.

INTRODUCTION: Antimicrobial peptides (AMPs) are valuable alternatives to traditional antibiotics, possess a variety of potent biological activities and exhibit immunomodulatory effects that alleviate difficult-to-treat infections. Clarifying the structure-activity relationships of AMPs can direct the synthesis of desirable peptide therapeutics. OBJECTIVES: In this study, the lipopolysaccharide-binding domain (LBD) was identified through machine learning-guided directed evolution, which acts as a functional domain of the anti-lipopolysaccharide factor family of AMPs identified from Marsupenaeus japonicus. METHODS: LBDA-D was identified as an output of this algorithm, in which the original LBDMj sequence was the input, and the three-dimensional solution structure of LBDB was determined using nuclear magnetic resonance. Furthermore, our study involved a comprehensive series of experiments, including morphological studies and in vitro and in vivo antibacterial tests. RESULTS: The NMR solution structure showed that LBDB possesses a circular extended structure with a disulfide crosslink at the terminus and two 310-helices and exhibits a broad antimicrobial spectrum. In addition, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that LBDB induced the formation of a cluster of bacteria wrapped in a flexible coating that ruptured and consequently killed the bacteria. Finally, coinjection of LBDB, Vibrio alginolyticus and Staphylococcus aureus in vivo improved the survival of M. japonicus, demonstrating the promising therapeutic role of LBDB for treating infectious disease. CONCLUSIONS: The findings of this study pave the way for the rational drug design of activity-enhanced peptide antibiotics.

Age-appropriate design of domestic intelligent medical products: An example of smart blood glucose detector for the elderly with AHP-QFD Joint KE.

Background: In response to the rise of intelligent products and the increasing prevalence of urban "empty nesters," we have developed a product specifically tailored for elderly diabetic patients. This product fulfils functional requirements and addresses stylistic preferences, contributing to the age-friendly evolution of home intelligent medical devices, particularly in intelligent blood glucose monitoring. Methods: Our approach commenced with a comprehensive user experience analysis to ascertain the needs of elderly users regarding home blood glucose meters. This involved constructing a hierarchy of user demands, followed by analysing and prioritising these needs. Utilizing Quality Function Deployment (QFD), we aligned user requirements with design specifications, identifying specific product functionalities and service design elements. Further, we employed Kansei Engineering (KE) to select sample designs that resonate with the concept of sensual imagery, leading to the derivation of specific modelling intentions. Combining these design elements, we proposed product design strategies and conducted practical case studies. The effectiveness of these designs was then assessed through fuzzy evaluation methods, allowing for user feedback. Results: Employing the Analytic Hierarchy Process for goal analysis, along with Quality Function Deployment theory and Kansei Engineering, we developed a home intelligent blood glucose meter catered to the elderly. This device not only meets its users' physiological and psychological needs but also provides an operationally convenient, health-conscious, and aesthetically pleasing experience. Conclusions: This methodology enhances the age-appropriate design of home-based smart glucose monitors for the elderly, offering innovative insights and optimization strategies for designing elderly-centric smart medical products.

High-density bin-based genetic map reveals a 530-kb chromosome segment derived from wild peanut contributing to late leaf spot resistance.

KEY MESSAGE: Twenty-eight QTLs for LLS disease resistance were identified using an amphidiploid constructed mapping population, a favorable 530-kb chromosome segment derived from wild species contributes to the LLS resistance. Late leaf spot (LLS) is one of the major foliar diseases of peanut, causing serious yield loss and affecting the quality of kernel and forage. Some wild Arachis species possess higher resistance to LLS as compared with cultivated peanut; however, ploidy level differences restrict utilization of wild species. In this study, a synthetic amphidiploid (Ipadur) of wild peanuts with high LLS resistance was used to cross with Tifrunner to construct TI population. In total, 200 recombinant inbred lines were collected for whole-genome resequencing. A high-density bin-based genetic linkage map was constructed, which includes 4,809 bin markers with an average inter-bin distance of 0.43 cM. The recombination across cultivated and wild species was unevenly distributed, providing a novel recombination landscape for cultivated-wild Arachis species. Using phenotyping data collected across three environments, 28 QTLs for LLS disease resistance were identified, explaining 4.35-20.42% of phenotypic variation. The major QTL located on chromosome 14, qLLS14.1, could be consistently detected in 2021 Jiyang and 2022 Henan with 20.42% and 12.12% PVE, respectively. A favorable 530-kb chromosome segment derived from Ipadur was identified in the region of qLLS14.1, in which 23 disease resistance proteins were located and six of them showed significant sequence variations between Tifrunner and Ipadur. Allelic variation analysis indicating the 530-kb segment of wild species might contribute to the disease resistance of LLS. These associate genomic regions and candidate resistance genes are of great significance for peanut breeding programs for bringing durable resistance through pyramiding such multiple LLS resistance loci into peanut cultivars.

Characterization of Fusarium solani associated with tobacco (Nicotiana tabacum L.) root rot in Henan, China.

The aim of this study was to characterize the Fusarium solani species complex (FSSC) population obtained from tobacco roots with root rot symptoms using morphological characteristics, molecular tests, and assessment of pathogenicity. Cultures isolated from roots were white to cream with sparse mycelium on PDA with colony growth of 21.5 ± 0.5 to 29.5 ± 0.5 mm after 3 days. Sporodochia were cream on carnation leaf agar (CLA) and spezieller nährstoffarmer agar (SNA), and macroconidia formed in sporodochia were 3- to 6-septate, straight to slightly curved, with wide central cells, a slightly short blunt apical cell, and a straight to almost cylindrical basal cell with a distinct foot shape, ranging in size from 20.92 to 64.37 µm × 3.91 to 6.57 µm. Microconidia formed on CLA were reniform and fusiform with 0 or 1 to occasionally 2 septa, that formed on long monophialidic conidiogenous cells, with a size range of 5.99 to 32.32 µm × 1.76 to 5.84 µm. Globose to oval chlamydospores were smooth to rough-walled, 6.5 to 13.3 ± 0.37 µm in diameter, terminal or intercalary, single or in pairs, occasionally in short chains on SNA. Molecular tests consisted of sequencing and phylogenetic analysis of the translation elongation factor-1 alpha (EF-1α), RNA polymerase II largest subunit (RPB1), and second largest subunit (RPB2) regions. All the obtained sequences revealed 98.14%~100% identity to Fusarium solani in both Fusarium ID and Fusarium MLST databases. Phylogenetic trees of the EF-1α gene and concatenated three-loci data showed that isolates from tobacco in Henan grouped in the proposed group 5, which is nested within FSSC clade 3 (FSSC 5). Twenty-seven of the 28 isolates caused a root rot of artificially inoculated tobacco seedlings, with a disease index ranging from 15.00 ± 1.67 to 91.11 ± 2.22. Cross pathogenicity tests showed that three representative isolates were virulent to six species of Solanaceae and two of Poaceae, with disease indexes ranging from 6.12 ± 0.56 to 84.44 ± 0.00, indicating that these isolates have a wide host range. The results may inform control of tobacco root rot through improved crop rotations.

A modified diffusion-weighted magnetic resonance imaging-based model from the radiologist's perspective: improved performance in determining the surgical resectability of advanced high-grade serous ovarian cancer.

BACKGROUND: Complete resection of all visible lesions during primary debulking surgery is associated with the most favorable prognosis in patients with advanced high-grade serous ovarian cancer. An accurate preoperative assessment of resectability is pivotal for tailored management. OBJECTIVE: This study aimed to assess the potential value of a modified model that integrates the original 8 radiologic criteria of the Memorial Sloan Kettering Cancer Center model with imaging features of the subcapsular or diaphragm and mesenteric lesions depicted on diffusion-weighted magnetic resonance imaging and growth patterns of all lesions for predicting the resectability of advanced high-grade serous ovarian cancer. STUDY DESIGN: This study included 184 patients with high-grade serous ovarian cancer who underwent preoperative diffusion-weighted magnetic resonance imaging between December 2018 and May 2023 at 2 medical centers. The patient cohort was divided into 3 subsets, namely a study cohort (n=100), an internal validation cohort (n=46), and an external validation cohort (n=38). Preoperative radiologic evaluations were independently conducted by 2 radiologists using both the Memorial Sloan Kettering Cancer Center model and the modified diffusion-weighted magnetic resonance imaging-based model. The morphologic characteristics of the ovarian tumors depicted on magnetic resonance imaging were assessed as either mass-like or infiltrative, and transcriptomic analysis of the primary tumor samples was performed. Univariate and multivariate statistical analyses were performed. RESULTS: In the study cohort, both the scores derived using the Memorial Sloan Kettering Cancer Center (intraclass correlation coefficients of 0.980 and 0.959, respectively; both P<.001) and modified diffusion-weighted magnetic resonance imaging-based models (intraclass correlation coefficients of 0.962 and 0.940, respectively; both P<.001) demonstrated excellent intra- and interobserver agreement. The Memorial Sloan Kettering Cancer Center model (odds ratio, 1.825; 95% confidence interval, 1.390-2.395; P<.001) and the modified diffusion-weighted magnetic resonance imaging-based model (odds ratio, 1.776; 95% confidence interval, 1.410-2.238; P<.001) independently predicted surgical resectability. The modified diffusion-weighted magnetic resonance imaging-based model demonstrated improved predictive performance with an area under the curve of 0.867 in the study cohort and 0.806 and 0.913 in the internal and external validation cohorts, respectively. Using the modified diffusion-weighted magnetic resonance imaging-based model, patients with scores of 0 to 2, 3 to 4, 5 to 6, 7 to 10, and ≥11 achieved complete tumor debulking rates of 90.3%, 66.7%, 53.3%, 11.8%, and 0%, respectively. Most patients with incomplete tumor debulking had infiltrative tumors, and both the Memorial Sloan Kettering Cancer Center and the modified diffusion-weighted magnetic resonance imaging-based models yielded higher scores. The molecular differences between the 2 morphologic subtypes were identified. CONCLUSION: When compared with the Memorial Sloan Kettering Cancer Center model, the modified diffusion-weighted magnetic resonance imaging-based model demonstrated enhanced accuracy in the preoperative prediction of resectability for advanced high-grade serous ovarian cancer. Patients with scores of 0 to 6 were eligible for primary debulking surgery.

Space-Efficient 3D Microalgae Farming with Optimized Resource Utilization for Regenerative Food.

Photosynthetic microalgae produce valuable metabolites and are a source of sustainable food that supports life without compromising arable land. However, the light self-shading, excessive water supply, and insufficient space utilization in microalgae farming have limited its potential in the inland areas most in need of regenerative food solutions. Herein, this work develops a 3D polysaccharide-based hydrogel scaffold for vertically farming microalgae without needing liquid media. This liquid-free strategy is compatible with diverse microalgal species and enables the design of living microalgal frameworks with customizable architectures that enhance light and water utilization. This approach significantly increases microalgae yield per unit water consumption, with an 8.8-fold increase compared to traditional methods. Furthermore, the dehydrated hydrogels demonstrate a reduced size and weight (≈70% reduction), but readily recover their vitality upon rehydration. Importantly, valuable natural products can be produced in this system including proteins, carbohydrates, lipids, and carotenoids. This study streamlines microalgae regenerative farming for low-carbon biomanufacturing by minimizing light self-shading, relieving water supply, and reducing physical footprints, and democratizing access to efficient aquatic food production.

OH2 oncolytic virus: A novel approach to glioblastoma intervention through direct targeting of tumor cells and augmentation of anti-tumor immune responses.

Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4+ and CD8+ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.

Identification of splicing factors signature predicting prognosis risk and the mechanistic roles of novel oncogenes in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is the most frequent subtype of head and neck cancer, generally with a poor prognosis and limited therapeutic options due to its highly heterogeneous malignancy. In this study, we screened functional splicing regulatory RNA binding proteins (RBPs) that were closely related with the prognosis of HNSCC patients and showed significant expression differences between HNSCC tumors and normal tissues. Based on this finding, we chose six candidate genes (HNRNPC, ZCRB1, RBM12B, SF3A2, SF3B3, and SRSF11) to generate a prognostic prediction model and validated the accuracy of the prognostic model for predicting patient survival outcomes. We found that the risk score predicted by our model can serve as an independent prognostic predictor. Notably, HNSCC tumors showing higher expression of SF3B3, HNRNPC, or ZCRB1 possessed higher risk scores in the discovered prediction model. The investigation of the underlying mechanism validated that knockdown of SF3B3, HNRNPC, and ZCRB1 separately induced a substantial impairment of HNSCC cell survival. Conversely, overexpression of each of the three genes promoted tumor cellular proliferation. High throughput RNA sequencing analysis revealed that changes in the expression of SF3B3 and HNRNPC remarkably affected alternative splicing of genes related to cell cycle regulation, whereas the depletion of ZCRB1 contributed to aberrant splicing events involving in DNA damage response. In addition, the prognostic prediction model's risk score was demonstrated to be related with the immune infiltration score. Particularly, SF3B3 has a negative correlation with CD8A expression. Therefore, our findings provide promising prognosis predictors and potential therapeutic targets for better treatment efficacy of HNSCC.

A long noncoding RNA functions in pumpkin fruit development through S-adenosyl-L-methionine synthetase.

Long non-coding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory roles of lncRNAs underlying fruit development have not been extensively studied. Pumpkin (Cucurbita spp.) is a preferred model for understanding the molecular mechanisms regulating fruit development because of its variable shape and size and large inferior ovary. Here, we performed strand-specific transcriptome sequencing on pumpkin (Curcurbita maxima 'Rimu') fruits at six developmental stages and identified 5425 reliably expressed lncRNAs. Among the 332 lncRNAs that were differentially expressed during fruit development, MSTRG.44863.1 was identified as a negative regulator of pumpkin fruit development. MSTRG.44863.1 showed a relatively high expression level and an obvious period-specific expression pattern. Transient overexpression and silencing of MSTRG.44863.1 significantly increased and decreased the content of 1-aminocyclopropane carboxylic acid (a precursor of ethylene) and ethylene production, respectively. RNA pull-down and microscale thermophoresis assays further revealed that MSTRG.44863.1 can interact with S-adenosyl-L-methionine synthetase (SAMS), an enzyme in the ethylene synthesis pathway. Considering that ethylene negatively regulates fruit development, these results indicate that MSTRG.44863.1 plays an important role in the regulation of pumpkin fruit development, possibly through interacting with SAMS and affecting ethylene synthesis. Overall, our findings provide a rich resource for further study of fruit-related lncRNAs while offering insight into the regulation of fruit development in plants.

A high-speed microscopy system based on deep learning to detect yeast-like fungi cells in blood.

Background: Blood-invasive fungal infections can cause the death of patients, while diagnosis of fungal infections is challenging. Methods: A high-speed microscopy detection system was constructed that included a microfluidic system, a microscope connected to a high-speed camera and a deep learning analysis section. Results: For training data, the sensitivity and specificity of the convolutional neural network model were 93.5% (92.7-94.2%) and 99.5% (99.1-99.5%), respectively. For validating data, the sensitivity and specificity were 81.3% (80.0-82.5%) and 99.4% (99.2-99.6%), respectively. Cryptococcal cells were found in 22.07% of blood samples. Conclusion: This high-speed microscopy system can analyze fungal pathogens in blood samples rapidly with high sensitivity and specificity and can help dramatically accelerate the diagnosis of fungal infectious diseases.

Blood-invasive fungal infections can be lethal and their diagnosis is challenging. The existing detection methods have shortcomings such as having unsatisfactory sensitivity, being time-consuming and having detection limitations. In this study, a high-speed microscopy system was constructed based on deep learning. With this system, fungal cells in the blood can be detected and quantified directly with much higher sensitivity than traditional microscopes. Also, the effect of antifungal treatment can be monitored.

Metagenomic exploration of the rhizosphere soil microbial community and their significance in facilitating the development of wild-simulated ginseng.

Panax ginseng, a prized medicinal herb, has faced increasingly challenging field production due to soil degradation and fungal diseases in Northeast China. Wild-simulated cultivation has prevailed because of its sustainable soil management and low disease incidence. Despite the recognized benefits of rhizosphere microorganisms in ginseng cultivation, their genomic and functional diversity remain largely unexplored. In this work, we utilized shotgun metagenomic analysis to reveal that Pseudomonadota, Actinomycetota, and Acidobacteriota were dominant in the ginseng rhizobiome and recovered 14 reliable metagenome-assembled genomes. Functional analysis indicated an enrichment of denitrification-associated genes, potentially contributing to the observed decline in soil fertility, while genes associated with aromatic carbon degradation may be linked to allelochemical degradation. Further analysis demonstrated enrichment of Actinomycetota in 9-year-old wild-simulated ginseng (WSG), suggesting the need for targeted isolation of Actinomycetota bacteria. Among these, at least three different actinomycete strains were found to play a crucial role in fungal disease resistance, with Streptomyces spp. WY144 standing out for its production of actinomycin natural products active against the pathogenic fungus Ilyonectria robusta. These findings not only enhance our understanding of the rhizobiome of WSG but also present promising avenues for combating detrimental fungal pathogens, underscoring the importance of ginseng in both medicinal and agricultural contexts.IMPORTANCEWild-simulated ginseng, growing naturally without human interference, is influenced by its soil microbiome. Using shotgun metagenomics, we analyzed the rhizospheric soil microbiome of 7- and 9-year-old wild-simulated ginseng. The study aimed to reveal its composition and functions, exploring the microbiome's key roles in ginseng growth. Enrichment analysis identified Streptomycetes in ginseng soil, with three strains inhibiting plant pathogenic fungi. Notably, one strain produced actinomycins, suppressing the ginseng pathogenic fungus Ilyonectria robusta. This research accelerates microbiome application in wild-simulated ginseng cultivation, offering insights into pathogen protection and supporting microbiome utilization in agriculture.