OsAAP8 mutation leads to significant improvement in the nutritional quality and appearance of rice grains.

Members of the permease gene family are responsible for important biological functions in the growth and development of rice. Here, we show that OsAAP8 is a constitutive expression gene, and its translated protein is localized on the cell membrane. Mutation of the OsAAP8 can promote the expression of genes related to protein and amylopectin synthesis, and also promote the enlargement of protein bodies in its endosperm, leading to an increase in the protein, amylopectin, and total amino acid content of grains in OsAAP8 mutants. Seeds produced by the OsAAP8 mutant were larger, and the chalkiness traits of the OsAAP8 mutants were significantly reduced, thereby improving the nutritional quality and appearance of rice grains. The OsAAP8 protein is involved in the transport of various amino acids; OsAAP8 mutation significantly enhanced the root absorption of a range of amino acids and might affect the distribution of various amino acids. Therefore, OsAAP8 is an important quality trait gene with multiple biological functions, which provides important clues for the molecular design of breeding strategies for developing new high-quality varieties of rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01473-w.

Lycopene promoted M2 macrophage polarization via inhibition of NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4 pathway in response to Escherichia coli infection in J744A.1 cells.

Escherichia coli (E. coli) can induce severe clinical bovine mastitis, which is to blame for large losses experienced by dairy farms. Macrophage polarization into various states is in response to pathogen infections. Lycopene, a naturally occurring hydrocarbon carotenoid, relieved inflammation by controlling M1/M2 status of macrophages. Thus, we wanted to explore the effect of lycopene on polarization states of macrophages in E. coli-induced mastitis. Macrophages were cultivated with lycopene for 24, before E. coli inoculation for 6 h. Lycopene (0.5 µmol/L) significantly enhanced cell viabilities and significantly reduced lactic dehydrogenase (LDH) levels in macrophages, whereas 2 and 3 µmol/L lycopene significantly enhanced LDH activities. Lycopene treatment significantly reduced the increase in LDH release, iNOS, CD86, TNF-α, IL-1ß and phosphatase and tensin homolog (PTEN) expressions in E. coli group. 0.5 µmol/L lycopene significantly increased E. coli-induced downregulation of CD206, arginase I (ARG1), indoleamine 2,3-dioxygenase (IDO), chitinase 3-like 3 (YM1), PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, jumonji domain-containing protein-3 (JMJD3) and interferon regulatory factor 4 (IRF4) levels. Moreover, Ginkgolic acid C17:1 (a specific PTEN inhibitor), 740YPDGFR (a specific PI3K activator), SC79 (a specific AKT activator) or CHPG sodium salt (a specific NF-κB activator) significantly decreased CD206, AGR1, IDO and YM1 expressions in lycopene and E. coli-treated macrophages. Therefore, lycopene increased M2 macrophages via inhibiting NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4 pathway in response to E. coli infection in macrophages. These results contribute to revealing the pathogenesis of E. coli-caused bovine mastitis, providing the new angle of the prevention and management of mastitis.

Metabolic characterization of sphere-derived prostate cancer stem cells reveals aberrant urea cycle in stemness maintenance.

Alteration of cell metabolism is one of the essential characteristics of tumor growth. Cancer stem cells (CSCs) are the initiating cells of tumorigenesis, proliferation, recurrence, and other processes, and play an important role in therapeutic resistance and metastasis. Thus, identification of the metabolic profiles in prostate cancer stem cells (PCSCs) is critical to understanding prostate cancer progression. Using untargeted metabolomics and lipidomics methods, we show distinct metabolic differences between prostate cancer cells and PCSCs. Urea cycle is the most significantly altered metabolic pathway in PCSCs, the key metabolites arginine and proline are evidently elevated. Proline promotes cancer stem-like characteristics via the JAK2/STAT3 signaling pathway. Meanwhile, the enzyme pyrroline-5-carboxylate reductase 1 (PYCR1), which catalyzes the conversion of pyrroline-5-carboxylic acid to proline, is highly expressed in PCSCs, and the inhibition of PYCR1 suppresses the stem-like characteristics of prostate cancer cells and tumor growth. In addition, carnitine and free fatty acid levels are significantly increased, indicating reprogramming of fatty acid metabolism in PCSCs. Reduced sphingolipid levels and increased triglyceride levels are also observed. Collectively, our data illustrate the comprehensive landscape of the metabolic reprogramming of PCSCs and provide potential therapeutic strategies for prostate cancer.

Enhanced osteogenesis and physicochemical properties of PMMA bone cement with SrBG/HA porous core-shell microspheres.

Artificial bone graft with osteoconductivity, angiogenesis, and immunomodulation is promising clinical therapeutics for the reluctant healing process of bone defects. Among various osteogenic substitutes, polymethyl methacrylate (PMMA) bone cement is a quit competitive platform due to its easy deployment to the bone defects with irregular shape and biomimetic mechanical properties. However, the biologically inert essence of PMMA is reliant on the passive osseointegration and cannot provide sufficient biologic cues to induce fast bone repair. Bioactive glass could serve as an efficient platform for the active osteogenesis of PMMA via ionic therapy and construction of alkaline microenvironment. However, the direct of deployment of bioactive glass into PMMA may trigger additional cytotoxicity and hinder cell growth on its surface. Hence we incorporated ionic therapy as osteogenic cue into the PMMA to enhance the biomedical properties. Specifically, we synthesized core-shell microspheres with a strontium-doped bioactive glass (SrBG) core and hydroxyapatite (HA) shell, and then composited them with PMMA to introduce multifunctional effects of HA incorporation, alkaline microenvironment construction, and functional ion release by adding microsphere. We preparedxSrBG@HA/PMMA cements (x= 30, 40, 50) with varied microsphere content and evaluated impacts on mechanical/handling properties, ion release, and investigated the impacts of different composite cements on proliferation, osteogenic differentiation, angiogenic potential, and macrophage polarization. These findings provide new perspectives and methodologies for developing advanced bone biomaterials to promote tissue regeneration.

Inhibitory Effect of Lactococcus and Enterococcus faecalis on Citrobacter Colitis in Mice.

Probiotics are beneficial for intestinal diseases. Research shows that probiotics can regulate intestinal microbiota and alleviate inflammation. Little research has been done on the effects of probiotics on colitis in mice. The purpose of this study was to investigate the inhibitory effect of the strains isolated and screened from the feces of healthy piglets on the enteritis of rocitrobacter. The compound ratio of isolated Lactobacillus L9 and Enterococcus faecalis L16 was determined, and the optimal compound ratio was selected according to acid production tests and bacteriostatic tests in vitro. The results showed that when the ratio of Lactobacillus L9 to Enterococcus faecalis L16 was 4:1, the pH value was the lowest, and the antibacterial diameter was the largest. Then, in animal experiments, flow cytometry was used to detect the number of T lymphocytes in the spleen and mesenteric lymph nodes of mice immunized with complex lactic acid bacteria. The results showed that the number of T lymphocytes in the spleen and mesenteric lymph nodes of mice immunized with complex lactic acid bacteria significantly increased, which could improve the cellular immunity of mice. The microbiota in mouse feces were sequenced and analyzed, and the results showed that compound lactic acid bacteria could increase the diversity of mouse microbiota. It stabilized the intestinal microbiota structure of mice and resisted the damage of pathogenic bacteria. The combination of lactic acid bacteria was determined to inhibit the intestinal colitis induced by Citrobacter, improve the cellular immune response of the body, and promote the growth of animals.

CRISPR/Cas9-mediated enhancement of semi-dwarf glutinous traits in elite Xiangdaowan rice (Oryza sativa L.): targeting SD1 and Wx genes for yield and quality improvement.

In rice cultivation, the traits of semi-dwarfism and glutinous texture are pivotal for optimizing yield potential and grain quality, respectively. Xiangdaowan (XDW) rice, renowned for its exceptional aromatic properties, has faced challenges due to its tall stature and high amylose content, resulting in poor lodging resistance and suboptimal culinary attributes. To address these issues, we employed CRISPR/Cas9 technology to precisely edit the SD1 and Wx genes in XDW rice, leading to the development of stable genetically homozygous lines with desired semi-dwarf and glutinous characteristics. The sd1-wx mutant lines exhibited reduced gibberellin content, plant height, and amylose content, while maintaining hardly changed germination rate and other key agronomic traits. Importantly, our study demonstrated that exogenous GA3 application effectively promoted growth by compensating for the deficiency of endogenous gibberellin. Based on this, a semi-dwarf glutinous elite rice (Oryza sativa L.) Lines was developed without too much effect on most agronomic traits. Furthermore, a comparative transcriptome analysis unveiled that differentially expressed genes (DEGs) were primarily associated with the anchored component of the membrane, hydrogen peroxide catabolic process, peroxidase activity, terpene synthase activity, and apoplast. Additionally, terpene synthase genes involved in catalyzing the biosynthesis of diterpenoids to gibberellins were enriched and significantly down-regulated. This comprehensive study provides an efficient method for simultaneously enhancing rice plant height and quality, paving the way for the development of lodging-resistant and high-quality rice varieties.

Quantified Metabolomics and Lipidomics Profiles Reveal Serum Metabolic Alterations and Distinguished Metabolites of Seven Chronic Metabolic Diseases.

The co-occurrence of multiple chronic metabolic diseases is highly prevalent, posing a huge health threat. Clarifying the metabolic associations between them, as well as identifying metabolites which allow discrimination between diseases, will provide new biological insights into their co-occurrence. Herein, we utilized targeted serum metabolomics and lipidomics covering over 700 metabolites to characterize metabolic alterations and associations related to seven chronic metabolic diseases (obesity, hypertension, hyperuricemia, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, fatty liver) from 1626 participants. We identified 454 metabolites were shared among at least two chronic metabolic diseases, accounting for 73.3% of all 619 significant metabolite-disease associations. We found amino acids, lactic acid, 2-hydroxybutyric acid, triacylglycerols (TGs), and diacylglycerols (DGs) showed connectivity across multiple chronic metabolic diseases. Many carnitines were specifically associated with hyperuricemia. The hypercholesterolemia group showed obvious lipid metabolism disorder. Using logistic regression models, we further identified distinguished metabolites of seven chronic metabolic diseases, which exhibited satisfactory area under curve (AUC) values ranging from 0.848 to 1 in discovery and validation sets. Overall, quantitative metabolome and lipidome data sets revealed widespread and interconnected metabolic disorders among seven chronic metabolic diseases. The distinguished metabolites are useful for diagnosing chronic metabolic diseases and provide a reference value for further clinical intervention and management based on metabolomics strategy.

Enhanced ·OH-Scavenging Activity of Cu-CeOx Nanozyme via Resurrecting Macrophage Nrf2 Transcriptional Activity Facilitates Diabetic Wound Healing.

Diabetic wounds are a prevalent and devastating complication of diabetes, which may impede their healing and regeneration. In diabetic wounds, excess reactive oxygen species (ROS) activate the nuclear factor kappa-B pathway, leading to transcriptional silencing of nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in a vicious cycle of oxidative stress and inflammation. Conventional nanozymes have limitations in preventing the continuous production of ROS, including the most oxidizing reactive hydroxyl radical (·OH), although they can remove pre-existing ROS. Herein, a novel antioxidant nanoplatform addresses this challenge by incorporating JSH-23 into the mesoporous of cupric-doped cerium oxide nanozymes. Additionally, for rapid wound adaptability and durable tissue adhesion, a nanozyme hydrogel spray consisting of oxidized sodium alginate and methacrylate gelatin is constructed, named OG@CCJs. This platform resurrects Nrf2 transcriptional activity of macrophages in vitro, curbing the production of ROS at its source, particularly ·OH, while enabling the nanozymes to scavenge previously generated ROS. OG@CCJs significantly alleviate oxidative stress in diabetic wounds in vivo, promoting wound healing. Overall, the proposed nanozyme-hydrogel spray with enhanced ·OH-scavenging activity uses a "two-track" antioxidant strategy to rebuild the antioxidant defense barrier of macrophages. This pioneering approach highlights the tremendous potential of OG@CCJs for facilitating diabetic wound healing.

Metal-Phenolic Networks-Reinforced Extracellular Matrix Scaffold for Bone Regeneration via Combining Radical-Scavenging and Photo-Responsive Regulation of Microenvironment.

The limited regulation strategies of the regeneration microenvironment significantly hinder bone defect repair effectiveness. One potential solution is using biomaterials capable of releasing bioactive ions and biomolecules. However, most existing biomaterials lack real-time control features, failing to meet high regulation requirements. Herein, a new Strontium (Sr) and epigallocatechin-3-gallate (EGCG) based metal-phenolic network with polydopamine (PMPNs) modification is prepared. This material reinforces a biomimetic scaffold made of extracellular matrix (ECM) and hydroxyapatite nanowires (nHAW). The PMPNs@ECM/nHAW scaffold demonstrates exceptional scavenging of free radicals and reactive oxygen species (ROS), promoting HUVECs cell migration and angiogenesis, inducing stem cell osteogenic differentiation, and displaying high biocompatibility. Additionally, the PMPNs exhibit excellent photothermal properties, further enhancing the scaffold's bioactivities. In vivo studies confirm that PMPNs@ECM/nHAW with near-infrared (NIR) stimulation significantly promotes angiogenesis and osteogenesis, effectively regulating the microenvironment and facilitating bone tissue repair. This research not only provides a biomimetic scaffold for bone regeneration but also introduces a novel strategy for designing advanced biomaterials. The combination of real-time photothermal intervention and long-term chemical intervention, achieved through the release of bioactive molecules/ions, represents a promising direction for future biomaterial development.

Why do only some cohort studies find health benefits from low volume alcohol use? A systematic review and meta-analysis of study characteristics that may bias mortality risk estimates.

OBJECTIVE: Assumptions about alcohol's health benefits profoundly influence global disease burden estimates and drinking guidelines. Utilising theory and evidence, we identify and test study characteristics that may bias estimates of all-cause mortality risk associated with low volume drinking. METHOD: We identified 107 longitudinal studies by systematic review with 724 estimates of association between alcohol consumption and all-cause mortality for 4,838,825 participants with 425,564 recorded deaths. "Higher quality" studies had a mean cohort age of ≤55 years, followed-up beyond 55 years, and excluded former and occasional drinkers from abstainer reference groups. "Low volume" alcohol use was defined as between one drink per week (>1.30g ethanol/day) and two drinks per day (<25g ethanol/day). Mixed linear regression was used to model relative risks (RRs) of mortality for subgroups of higher versus lower quality studies. RESULTS: As predicted, studies with younger cohorts and separating former and occasional drinkers from abstainers estimated similar mortality risk for low volume drinkers (RR=0.98, 0.87-1.11) as abstainers. Studies not meeting these quality criteria estimated significantly lower risk for low volume drinkers (RR=0.84, 0.79-0.89). In exploratory analyses, studies controlling for smoking and/or socio-economic status had significantly reduced mortality risks for low volume drinkers. However, mean RR estimates for low volume drinkers in non-smoking cohorts were above 1.0 (RR=1.16, 0.91-1.41). CONCLUSIONS: Studies with lifetime selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks. Future research should investigate whether smoking status mediates, moderates or confounds alcohol-mortality risk relationships.

Biomimetic Targeting Nanoadjuvants for Sonodynamic and Chronological Multi-Immunotherapy against Holistic Biofilm-Related Infections.

Biofilm-related infections (BRIs) present significant challenges owing to drug resistance, adverse immune responses, and implant failure; however, current approaches inadequately cater to the diverse therapeutic requirements at different stages of infection. To address this issue, a multi-immunotherapy strategy in combination with sonodynamic therapy is proposed for the chronological treatment of BRIs. Macrophage membrane-decorated targeting sonosensitive nanoadjuvants are fabricated to load cytosine-phosphate-guanine oligodeoxynucleotide (CPG-ODN) or microRNA (miR)-21-5p. In the early stages of BRI (Stage I), CPG-ODN-loaded nanoadjuvants (CPG@HMPN@M) promote the formation of neutrophil extracellular traps to capture and neutralize detached microbes. During the late stage of infection (Stage II), CPG-ODNs redirect macrophage polarization into the M1 phase to combat infections via TLR9/Myd88/TRAF6 pathway. During these stages, CPG@HMPN@M generates singlet oxygen through sonodynamic processes, eradicating the biofilms under US irradiation. Once the BRIs are eliminated, miR-21-5p-loaded nanoadjuvants (miR@HMPN@M) are delivered to the lesions to suppress excessive inflammation and promote tissue integration by evoking macrophage M2 polarization during the repair phase (Stage III) through PTEN/PI3K/Akt pathway. This innovative approach aims to provide comprehensive treatment strategies for the chronological treatment of BRI by effectively eliminating infections, promoting tissue restoration, and implementing different immune regulations at different stages, thus demonstrating promising clinical value.

Evaluation of the hygiene status of teaching environment in primary and secondary schools in Beijing City from 2016 to 2020 / 中国学校卫生

Objective@#To understand the trend of changes of hygiene status in the teaching environment among primary and secondary schools in Beijing City during 2016-2020, so as to provide basis for further improving the teaching environment and campus hygiene conditions in primary and secondary schools.@*Methods@#A proportional systematic sampling method covered over 50% of schools selected annually in Beijing from 2016 to 2019, and 34% were selected in 2020. Two representative classrooms were selected from each selected school for testing based on their structure and other factors, with 6 196 classrooms supervised, from 2016 to 2020,1 330,1 312,1 384,1 322,848 classrooms were monitored for each year.@*Results@#From 2016 to 2020, the overall lighting qualification rate of classrooms (lighting coefficient 72.8%, window to floor area ratio 41.8%, rear wall reflectance ratio 42.2%, blackboard reflection ratio 37.4%), the overall qualification rate of average blackboard illumination and uniformity (50.6%, 34.9 %), and the overall qualification rate of desk and chair allocation (58.6%) were all below 80%. The overall qualification rate of per capita classroom area (87.5%), blackboard size (83.2%), average desk illumination ( 80.1% ), average desk illumination and uniformity (82.9%), the distance between lamp and desk (99.1%), carbon dioxide ( 86.6% ), temperature (84.9%), and noise (96.6%) were all above 80%. The following indicators, blackboard size, the distance between lamp and desk, average blackboard illumination, lighting coefficient, blackboard reflectance, rear wall reflectance, carbon dioxide, temperature, and noise ( χ 2=78.38, 9.71, 11.76, 320.59, 37.63, 58.45, 236.45, 1 347.56, 101.97), had statistically significance between years. Among those indicators, the qualified rates of blackboard size, blackboard reflectance, lighting coefficient, and noise had been increasing year by year ( χ 2 trend =69.98, 15.82, 240.02, 5.77) ( P <0.05). The qualified rates of per capita classroom area, window to floor area ratio, and blackboard reflection ratio in primary schools (81.6%, 39.8%, 36.3%) were all lower than those in secondary schools (94.9%, 44.5%, 40.3%) ( χ 2=246.32, 12.03, 10.51, P <0.05). The qualified rates of blackboard size, average blackboard illumination, average blackboard illumination and uniformity, and desk and chair allocation (89.3%, 55.6% , 36.0%, and 60.2%) were all higher than those in secondary schools (75.4%, 44.1%, 33.3%, and 56.5%) ( χ 2=209.33, 78.41, 4.44, 8.22) ( P <0.05). The qualified rates of average desk illumination and uniformity, average blackboard illumination, rear wall reflectance ratio, desk and chair allocation, carbon dioxide, temperature, and noise indicators in urban area (82.9%, 84.1% , 51.9%, 45.0%, 60.9%, 91.2%, 89.5%, 97.8%) were all higher than those in suburban area (77.3%, 81.7%, 49.2%, 39.5%, 56.3%, 82.3%, 80.4%, 95.5%) ( χ 2=31.16, 6.28, 4.36, 16.40, 13.39, 105.29, 98.23, 24.66， P <0.05). The qualified rates of the distance between lamp and desk, lighting coefficient, window to floor area ratio, blackboard size, blackboard reflection ratio, average blackboard illumination and uniformity, and per capita classroom area in urban areas (98.8%, 65.2%, 34.3%, 76.7%, 35.9%, 30.1%, 84.6%) were all lower than those in suburban areas (99.4%, 81.4%, 49.8%, 89.7%, 40.2%, 39.6%, 90.3%) ( χ 2=6.80, 171.67, 132.43, 188.46 , 12.45, 60.28, 44.82) ( P <0.05).@*Conclusions@#The main problems in the teaching environment of schools in Beijing are classroom lighting, as well as desk and chair allocation. The findings suggest technical rationality and operability of relevant standard should be considered when under revision, and standard training and supervision management should be strengthened, with the aim of teaching environment improvement.

Analysis of associated factors of attempting e-cigarettes use among senior high school students in Beijing City between 2019 and 2023 / 中国学校卫生

Objective@#To analyze prevalence and associated factors of attempting e cigarettes use among senior high school students in Beijing City between 2019 and 2023, in order to providing references for the construction of smoke free senior high schools environments.@*Methods@#In 2019, 9 137 students from 44 senior high schools in Beijing City were monitored, including 27 general senior high schools and 17 vocational senior high schools. In 2023, the study included 6 709 students from 30 senior high schools comprising 21 general senior high schools and 9 vocational senior high schools. On site investigations using anonymous questionnaires were conducted. The monitoring content included demographic information, second hand smoke exposure, tobacco product use and tobacco awareness. Chi square test was used to compare the differences of various indicators in different groups, and multivariate Logistic regression analysis was adopted to analysis the influencing factors among senior high school students attempting to use e cigarettes between 2019 and 2023.@*Results@#In 2019, the rates of vocational senior high school and general senior high school students attempting to use e-cigarettes were 22.57% and 9.78%, respectively. In 2023, it decreased to 14.39% and 6.43%, respectively. In 2019 ( OR =1.59,95% CI =1.35-1.88) and 2023 ( OR =1.71,95% CI =1.38-2.11), vocational senior high school students both hold higher risk of attempting to use e-cigarettes,compared with general senior high school students. In 2019, non-indigenous senior high school students attempting to use e cigarettes were more than indigenous senior high school students ( OR = 1.28 , 95% CI =1.05-1.56). In 2019 ( OR =1.62, 95% CI =1.34-1.95) and 2023 ( OR =1.77, 95% CI =1.35-2.31), smoking anywhere in households increased the risk of attempting to use e-cigarettes among senior high school students. In both 2019 and 2023, not attempting to smoke cigarettes ( OR =0.24,95% CI =0.21-0.29; OR =0.15,95% CI =0.11-0.19), not currently smoking cigarettes ( OR =0.29,95% CI =0.22-0.40; OR =0.30,95% CI =0.17-0.53), not being exposed to secondhand smoke in school ( OR =0.62, 95% CI = 0.53 -0.72; OR =0.51, 95% CI =0.41-0.64) or in outdoor public places ( OR =0.74, 95% CI =0.63-0.86; OR = 0.62 , 95% CI =0.50-0.78) all reduced the risk of attempting to use e-cigarettes among senior hgih school students( P <0.05).@*Conclusion@#The influencing factors of attempts by senior high school students in Beijing City to use e-cigarettes are generally consistent between 2023 and 2019, with a focus on vocational senior high schools to ensure the continuity of intervention measures and promote the construction of smoke free senior high schools.

Z-Ligustilide Combined with Cisplatin Reduces PLPP1-Mediated Phospholipid Synthesis to Impair Cisplatin Resistance in Lung Cancer.

Lung cancer is a malignant tumor with one of the highest morbidity and mortality rates in the world. Approximately 80-85% of lung cancer is diagnosed as non-small lung cancer (NSCLC), and its 5-year survival rate is only 21%. Cisplatin is a commonly used chemotherapy drug for the treatment of NSCLC. Its efficacy is often limited by the development of drug resistance after long-term treatment. Therefore, determining how to overcome cisplatin resistance, enhancing the sensitivity of cancer cells to cisplatin, and developing new therapeutic strategies are urgent clinical problems. Z-ligustilide is the main active ingredient of the Chinese medicine Angelica sinensis, and has anti-tumor activity. In the present study, we investigated the effect of the combination of Z-ligustilide and cisplatin (Z-ligustilide+cisplatin) on the resistance of cisplatin-resistant lung cancer cells and its mechanism of action. We found that Z-ligustilide+cisplatin decreased the cell viability, induced cell cycle arrest, and promoted the cell apoptosis of cisplatin-resistant lung cancer cells. Metabolomics combined with transcriptomics revealed that Z-ligustilide+cisplatin inhibited phospholipid synthesis by upregulating the expression of phospholipid phosphatase 1 (PLPP1). A further study showed that PLPP1 expression was positively correlated with good prognosis, whereas the knockdown of PLPP1 abolished the effects of Z-ligustilide+cisplatin on cell cycle and apoptosis. Specifically, Z-ligustilide+cisplatin inhibited the activation of protein kinase B (AKT) by reducing the levels of phosphatidylinositol 3,4,5-trisphosphate (PIP3). Z-ligustilide+cisplatin induced cell cycle arrest and promoted the cell apoptosis of cisplatin-resistant lung cancer cells by inhibiting PLPP1-mediated phospholipid synthesis. Our findings demonstrate that the combination of Z-Ligustilide and cisplatin is a promising approach to the chemotherapy of malignant tumors that are resistant to cisplatin.

OsNAC74 affects grain protein content and various biological traits by regulating OsAAP6 expression in rice.

The grain protein content is an important quality trait in cereals, and the expression level of the OsAAP6 can significantly affect the grain protein content in rice. Through site-directed mutagenesis, we found that the position from -7 to -12 bp upstream of the transcription start site of the OsAAP6 was the functional variation site. By using the yeast single hybrid test, point-to-point in yeast, and the local surface plasmon resonance test, the OsNAC74 was screened and verified to be a regulator upstream of OsAAP6. The OsNAC74 is a constitutively expressed gene whose product is located on the cell membrane. The OsAAP6 and the genes related to the seed storage in the Osnac74 mutants were downregulated, and grain protein content was significantly reduced. In addition, OsNAC74 had a significant impact on quality traits such as grain chalkiness and gel consistency in rice. Although the Osnac74 mutant seeds were relatively small, the individual plant yield was not decreased. Therefore, OsNAC74 is an important regulatory factor with multiple biological functions. This study provides important information for the later use of OsNAC74 gene for molecular design and breeding in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01433-w.

Efficacy and Safety of PD-1/PD-L1 Inhibitor and Chemotherapy in Treatment of Advanced Small Cell Lung Cancer.

Context: SCLC has had few drugs for treatment and a high malignancy rate. About two-thirds of SCLC patients have distant metastasis by the time they receive a diagnosis, and once it occurs, patient's survival time is short. Immunotherapy treatments can block immunosuppression and increase the body's antitumor ability. PD-1 is the main immune checkpoint of tumors' immune response, and PD-L1 is one of the ligands of PD-1. Objective: The study intended to analyze the therapeutic effects of inhibitors of programmed death-1 (PD-1)/ programmed cell death 1 ligand 1 (PD-L1) combined with chemotherapy for patients with advanced small cell lung cancer (SCLC), evaluate the safety of that treatment, and compare it with chemotherapy alone. Design: The research team performed a retrospective randomized controlled study. Setting: The study took place at Cangzhou Central Hospital. Participants: Participants were 72 patients with advanced SCLC who received treatment at the hospital between December 2021 and December 2022. Intervention: The research team divided participants into two groups, each with 36 participants, using the random number method: (1) the control group, which received platinum-etoposide chemotherapy, and (2) the intervention group, which received a PD-1/PD-L1 inhibitor combined with the same chemotherapy that the control group received. Outcome Measures: The research team examined: (1) short-term efficacy; (2) long-term efficacy; (3) tumor-marker levels-neuron-specific enolase (NSE), progastrin releasing peptide (ProGRP), cytokeratin-19-fragment (CYFRA21-1), and squamous cell carcinoma antigen (SCCA); (4) T lymphocyte-subset levels-cluster of differentiation 3+ (CD3+), CD4+, and CD8+; (5) adverse reactions, and (6) Karnofsky performance status (KPS) scores. Results: Compared with the control group, the intervention group's: (1) overall response rate (ORR), with P = .002, and disease control rate (DCR), with P = .041, were significantly higher; (2) median survival time was significantly longer (P = .035); (3) levels of NSE, ProGRP, CYFRA21-1, and SCCA were significantly lower (all P < .001); (4) levels of CD3+ (P = .043) and CD4+ (P < .001) levels were significantly higher; and (5) Karnofsky performance status (KPS) scores were significantly higher than those of the control group (P = .018). No difference existed in the number of adverse reactions between the groups (P > .05). Conclusions: The PD-1/PD-L1 inhibitor combined with chemotherapy can benefit advanced SCLC patients, controlling patients' conditions and improving their quality of life, with good safety.

Targeting CDH17 with Chimeric Antigen Receptor-Redirected T Cells in Small Cell Lung Cancer.

BACKGROUND: Chimeric antigen receptor T cell (CAR-T) therapy stands as a precise and targeted approach in the treatment of malignancies. In this study, we investigated the feasibility of targeting Cadherin 17 (CDH17) with CDH17 CAR-T cells as a therapeutic modality for small cell lung cancer (SCLC). METHODS: CDH17 expression levels were assessed in human SCLC tumor tissues and cell lines using qPCR and Western blot. Subsequently, we established CDH17 CAR-T cells and assessed their cytotoxicity by co-culturing them with various SCLC cell lines at different effector-to-target (E:T) ratios, complemented by ELISA assays. To ascertain the specificity of CDH17 CAR-T cells, we conducted experiments on SCLC cells with and without CDH17 expression (shRNAs). Furthermore, we employed an SCLC xenograft model to evaluate the in vivo efficacy of CDH17 CAR-T cells. RESULTS: Our results revealed a significant upregulation of CDH17 in both SCLC tissues and cell lines. CDH17 CAR-T cells exhibited robust cytotoxic activity against SCLC cells in vitro, while demonstrating no cytotoxicity towards CDH17-deficient SCLC cells and HEK293 cells that lack CDH17 expression. Importantly, the production of IFN-γ and TNF-α by CDH17 CAR-T cells correlated with their cytotoxic potency. Additionally, treatment with CDH17 CAR-T cells significantly decelerated the growth rate of SCLC-derived xenograft tumors in vivo. Remarkably, no significant difference in body weight was observed between the control group and the group treated with CDH17 CAR-T cells. CONCLUSIONS: The preclinical data open further venues for the clinical use of CDH17 CAR-T cells as an immunotherapeutic strategy for SCLC treatment.

Biofilm electrode reactor coupled manganese ore substrate up-flow microbial fuel cell-constructed wetland system: High removal efficiencies of antibiotic, zinc (II), and the corresponding antibiotic resistance genes.

A coupled system comprised of a biofilm electrode reactor (BER) and a manganese ore substrate microbial fuel cell-constructed wetland (MFC-CW) system was used to remove co-exposed antibiotic and Zn (II), as well as simultaneously reduce copies of antibiotic resistance genes (ARGs) in the current study. In this system, BER primarily reduced the concentrations of antibiotics and Zn (II), and the effluent was used as the input to the MFC-CW, thereby providing electricity to BER. Co-exposure to a high concentration of Zn (II) decreased the relative abundances (RAs) of ARGs in the BER effluent, whereas the remaining sub-lethal concentration of Zn (II) increased the RAs of ARGs in the MFC-CW effluent. Even though the absolute copies of ARGs in the effluents increased during co-exposure, the total number of target ARG copies in the effluent of MFC-CW was significantly lower than that of BER. Moreover, BER pre-treatment eliminated most of Zn (II), which improved the electrical power generation characteristic of the MFC-CW unit. Correspondingly, the bacterial community and the ARGs hosts were analyzed to demonstrate the mechanism. In conclusion, the coupled system demonstrates significant potential to reduce antibiotics, Zn (II) and environmental risks posed by ARGs.