Photosynthetic plasticity aggravates the susceptibility of magnesium-deficient leaf to high light in rapeseed plants: the importance of Rubisco and mesophyll conductance.

Plants grown under low magnesium (Mg) soils are highly susceptible to encountering light intensities that exceed the capacity of photosynthesis (A), leading to a depression of photosynthetic efficiency and eventually to photooxidation (i.e., leaf chlorosis). Yet, it remains unclear which processes play a key role in limiting the photosynthetic energy utilization of Mg-deficient leaves, and whether the plasticity of A in acclimation to irradiance could have cross-talk with Mg, hence accelerating or mitigating the photodamage. We investigated the light acclimation responses of rapeseed (Brassica napus) grown under low- and adequate-Mg conditions. Magnesium deficiency considerably decreased rapeseed growth and leaf A, to a greater extent under high than under low light, which is associated with higher level of superoxide anion radical and more severe leaf chlorosis. This difference was mainly attributable to a greater depression in dark reaction under high light, with a higher Rubisco fallover and a more limited mesophyll conductance to CO2 (gm ). Plants grown under high irradiance enhanced the content and activity of Rubisco and gm to optimally utilize more light energy absorbed. However, Mg deficiency could not fulfill the need to activate the higher level of Rubisco and Rubisco activase in leaves of high-light-grown plants, leading to lower Rubisco activation and carboxylation rate. Additionally, Mg-deficient leaves under high light invested more carbon per leaf area to construct a compact leaf structure with smaller intercellular airspaces, lower surface area of chloroplast exposed to intercellular airspaces, and CO2 diffusion conductance through cytosol. These caused a more severe decrease in within-leaf CO2 diffusion rate and substrate availability. Taken together, plant plasticity helps to improve photosynthetic energy utilization under high light but aggravates the photooxidative damage once the Mg nutrition becomes insufficient.

Mitophagy bridges DNA sensing with metabolic adaption to expand lung cancer stem-like cells.

While previous studies have identified cancer stem-like cells (CSCs) as a crucial driver for chemoresistance and tumor recurrence, the underlying mechanisms for populating the CSC pool remain unclear. Here, we identify hypermitophagy as a feature of human lung CSCs, promoting metabolic adaption via the Notch1-AMPK axis to drive CSC expansion. Specifically, mitophagy is highly active in CSCs, resulting in increased mitochondrial DNA (mtDNA) content in the lysosome. Lysosomal mtDNA acts as an endogenous ligand for Toll-like receptor 9 (TLR9) that promotes Notch1 activity. Notch1 interacts with AMPK to drive lysosomal AMPK activation by inducing metabolic stress and LKB1 phosphorylation. This TLR9-Notch1-AMPK axis supports mitochondrial metabolism to fuel CSC expansion. In patient-derived xenograft chimeras, targeting mitophagy and TLR9-dependent Notch1-AMPK pathway restricts tumor growth and CSC expansion. Taken together, mitochondrial hemostasis is interlinked with innate immune sensing and Notch1-AMPK activity to increase the CSC pool of human lung cancer.

Sufficient potassium improves inorganic phosphate-limited photosynthesis in Brassica napus by enhancing metabolic phosphorus fractions and Rubisco activity.

Crop photosynthesis (A) and productivity are often limited by a combination of nutrient stresses, such that changes in the availability of one nutrient may affect the availability of another nutrient, in turn influencing A. In this study, we examined the synergistic effects of phosphorus (P) and potassium (K) on leaf A in a nutrient amendment experiment, in which P and K were added individually or in combination to Brassica napus grown under P and K co-limitation. The data revealed that the addition of P gradually removed the dominant limiting factor (i.e. the limited availability of P) and improved leaf A. Strikingly, the addition of K synergistically improved the overall uptake of P, mainly by boosting plant growth, and compensated for the physiological demand for P by prioritizing investment in metabolic pools of P (P-containing metabolites and inorganic phosphate, Pi). The enlarged pool of metabolically active P was partially associated with the upregulation of Pi regeneration through release from triose phosphates rather than replacement of P-containing lipids. This process mitigated P restrictions on A by maintaining the ATP/NADPH and NADPH/NADP+ ratios and increasing the content and activity of Rubisco. Our findings demonstrate that sufficient K increased Pi-limited A by enhancing metabolic P fractions and Rubisco activity. Thus, ionic synergism may be exploited to mitigate nutrient-limiting factors to improve crop productivity.

Pulmonary microbial spectrum in late-stage SARS-CoV-2 infection: a case series.

Coronavirus disease 2019 (COVID-19), a kind of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily spreads through the respiratory tract from human to human. Its extensive and rapid spread has led to a global pandemic, causing great harm to human health and economic development all over the world. Current known evidence indicates that SARS-CoV-2 has evolved accumulating multiple mutations, with altered infectivity and viral replication capacity. A better understanding of the complications of COVID-19 and its relationship with underlying diseases is crucial for the prevention and treatment of SARS-CoV-2. This case series reviewed case data of our 4 recent patients with severe or critical COVID-19, including treatment plan, status of pulmonary infection and their microbiology workup with metagenomic next-generation sequencing with bronchoalveolar lavage fluid. This report shed light on the significance of rapid and accurate clinical diagnosis and treatment on COVID-19.

Potassium deficiency enhances imbalances in rice water relations under water deficit by decreasing leaf hydraulic conductance.

Potassium (K+) is an essential macronutrient for appropriate plant development and physiology. However, little is known about the mechanisms involved in the regulation of leaf water relations by K under water deficit. A pot experiment with two K supplies of 0.45 and 0 g K2O per pot (3 kg soil per pot) and two watering conditions (well-watered and water-deficit) was conducted to explore the effects of K deficiency on canopy transpiration characteristics, leaf water status, photosynthesis, and hydraulic traits in two rice genotypes with contrasting resistance to drought. The results showed that K deficiency reduced canopy transpiration rate by decreasing stomatal conductance, which led to higher canopy temperatures, resulting in limited water deficit tolerance in rice. In addition, K deficiency led to further substantial reductions in leaf relative water content and water potential under water deficit, which increased the imbalance in leaf water relations under water deficit. Notably, K deficiency limited leaf gas exchange by reducing leaf hydraulic conductance, but decreased the intrinsic water use efficiency under water deficit, especially for the drought-resistant cultivar. Further analysis of the underlying process of leaf hydraulic resistance revealed that the key limiting factor of leaf hydraulic conductance under K deficiency was the outside-xylem hydraulic conductance rather than the xylem hydraulic conductance. Overall, our results provide a comprehensive perspective for assessing leaf water relations under K deficiency, water deficit, and their combined stresses, which will be useful for optimal rice fertilization strategies.

Bibliometric analysis of the global trends in immune-related recurrent pregnancy loss research over the last two decades.

PROBLEM: A comprehensive analysis was conducted to explore the scientific output on immune-related recurrent pregnancy loss (RPL) and its key aspects. Despite the lack of clear explanations for most RPL cases, immune factors were found to play a significant role. METHOD OF STUDY: The study utilized a bibliometric approach, searching the Web of Science Core Collection database for relevant literature published between 2004 and 2023. RESULTS: The collected dataset consisted of 2228 articles and reviews, revealing a consistent increase in publications and citations over the past two decades. The analysis identified the United States and China as the most productive countries in terms of RPL research. Among the institutions, Fudan University in China emerged as the top contributor, followed by Shanghai Jiaotong University. Kwak-kim J was the most prolific author, while Christiansen Ob had the highest number of co-citations. The top 25 co-cited references on diagnosis, treatment, and mechanisms formed the foundation of knowledge in this field. By examining keyword co-occurrence and co-citations, the study found that antiphospholipid syndrome and natural killer cells were the primary areas of focus in immune-related RPL research. Additionally, three emerging hotspots were identified: chronic endometritis, inflammation, and decidual macrophages. These aspects demonstrated increasing interest and research activity within the field of immune-related RPL. CONCLUSIONS: Overall, this comprehensive bibliometric analysis provided valuable insights into the patterns, frontiers, and focal points of global scientific output related to immune-related RPL.

Dihydroartemisinin-driven TOM70 inhibition leads to mitochondrial destabilization to induce pyroptosis against lung cancer.

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

Comparison of self-efficacy among graduate teaching assistants before and after training.

BACKGROUND: Teaching assistants (TAs) play a crucial role in pedagogical practices, and the TA training has emerged as a vital strategy for enhancing teaching quality and fostering effective interactions. The self-efficacy of TAs can substantially impact their performance. Nevertheless, little research has focused on the change in TAs' self-efficacy following their training. METHODS: A self-control quasi-experiment was conducted to examine shifts in the self-efficacy of Tas at Peking University before and after their TA training. A questionnaire was used to assess the change, and the reliability and validity of the questionnaire was also calculated. A paired data rank sum test was used to analysis the changes in TA self-efficacy before and after training. RESULTS: A total of 372 TAs from School of Basic Medicine (N = 173), School of Pharmacy (N = 112), School of Public Health (N = 69), and other schools (N = 18) submitted complete questionnaires. The questionnaire showed a good performance in internal reliability and validity test (Cronbach's alpha index = 0.906, and KMO value was 0.903). Participants had a median total self-efficacy score of 88 and 85 before and after the TA training, respectively, which shows a lack in the total TA self-efficacy score following the TA training (P < 0.001). TAs who have no desire to becoming a college instructor have a higher self-efficacy when compared to TAs who have expressed neutral attitudes in becoming college instructors. CONCLUSION: The participated TAs display a lack of self-efficacy after attending the TA training at Peking University. Therefore, it is necessary to establish and strengthen TA's self-efficacy beyond academic skills when designing and delivering TA training programs at Peking University.

Chicken Interferon-Alpha and -Lambda Exhibit Antiviral Effects against Fowl Adenovirus Serotype 4 in Leghorn Male Hepatocellular Cells.

Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens.

Predictive model for assessing malnutrition in elderly hospitalized cancer patients: A machine learning approach.

BACKGROUND: Malnutrition is prevalent among elderly cancer patients. This study aims to develop a predictive model for malnutrition in hospitalized elderly cancer patients. METHODS: Data from January 2022 to January 2023 on cancer patients aged 60+ were collected, involving 22 variables. Key variables were identified using the LASSO (Least Absolute Shrinkage and Selection Operator) method, and nine machine learning models were tested. SHAP was used to interpret the XGBoost model. Malnutrition prevalence was assessed. RESULTS: Among 450 participants, 46.4 % were malnourished. Key predictors identified were ADL (Activities of Daily Living), ALB (Albumin), BMI (Body Mass Index) and age. XGBoost had the highest AUC of 0.945, accuracy of 0.872, and sensitivity of 0.968. Higher ADL and age increased malnutrition risk, while lower ALB and BMI reduced it. CONCLUSIONS: The XGBoost model is highly effective in detecting malnutrition in elderly cancer patients, enabling early and rapid nutritional assessments.

Ubiquitination on Lysine 247 of Newcastle Disease Virus Matrix Protein Enhances Viral Replication and Virulence by Driving Nuclear-Cytoplasmic Trafficking.

The Newcastle disease virus (NDV) matrix (M) protein is the pivotal element for viral assembly, budding, and proliferation. It traffics through the cellular nucleus but performs its primary function in the cytoplasm. To investigate the biological importance of M protein nuclear-cytoplasmic trafficking and the mechanism involved, the regulatory motif nuclear export signal (NES) and nuclear localization signal (NLS) were analyzed. Here, two types of combined NLSs and NESs were identified within the NDV-M protein. The Herts/33-type M protein was found to mediate efficient nuclear export and stable virus-like particle (VLP) release, while the LaSota-type M protein was retained mostly in the nuclei and showed retarded VLP production. Two critical residues, namely, 247 and 263, within the motif were identified and associated with nuclear export efficiency. We identified, for the first time, residue 247 as an important monoubiquitination site, of which its modification regulates the nuclear-cytoplasmic trafficking of NDV-M. Subsequently, mutant LaSota strains were rescued via reverse genetics, which contained either single or double amino acid substitutions that were similar to the M of Herts/33. The rescued LaSota (rLaSota) strains rLaSota-R247K, -S263R, and -double mutation (DM) showed about 2-fold higher hemagglutination (HA) titers and 10-fold higher 50% egg infective dose (EID50) titers than wild-type (wt) rLaSota. Furthermore, the mean death time (MDT) and intracerebral pathogenicity index (ICPI) values of those recombinant viruses were slightly higher than those of wt rLaSota probably due to their higher proliferation rates. Our findings contribute to a better understanding of the molecular mechanism of the replication and pathogenicity of NDV and even those of all other paramyxoviruses. This information is beneficial for the development of vaccines and therapies for paramyxoviruses. IMPORTANCE Newcastle disease virus (NDV) is a pathogen that is lethal to birds and causes heavy losses in the poultry industry worldwide. The World Organization for Animal Health (OIE) ranked Newcastle disease (ND) as the third most significant poultry disease and the eighth most important wildlife disease in the World Livestock Disease Atlas in 2011. The matrix (M) protein of NDV is very important for viral assembly and maturation. It is interesting that M proteins enter the cellular nucleus before performing their primary function in the cytoplasm. We found that NDV-M has a combined nuclear import and export signal. The ubiquitin modification of a lysine residue within this signal is critical for quick, efficient nuclear export and subsequent viral production. Our findings shed new light on viral replication and open up new possibilities for therapeutics against NDV and other paramyxoviruses; furthermore, we demonstrate a novel approach for improving paramyxovirus vaccines.

METTL3-mediated m6A RNA methylation induces the differentiation of lung resident mesenchymal stem cells into myofibroblasts via the miR-21/PTEN pathway.

BACKGROUND: The accumulation of myofibroblasts is the key pathological feature of pulmonary fibrosis (PF). Aberrant differentiation of lung-resident mesenchymal stem cells (LR-MSCs) has been identified as a critical source of myofibroblasts, but the molecular mechanisms underlying this process remain largely unknown. In recent years, N6-methyladenosine (m6A) RNA modification has been implicated in fibrosis development across diverse organs; however, its specific role in promoting the differentiation of LR-MSCs into myofibroblasts in PF is not well defined. METHODS: In this study, we examined the levels of m6A RNA methylation and the expression of its regulatory enzymes in both TGF-ß1-treated LR-MSCs and fibrotic mouse lung tissues. The downstream target genes of m6A and their related pathways were identified according to a literature review, bioinformatic analysis and experimental verification. We also assessed the expression levels of myofibroblast markers in treated LR-MSCs and confirmed the involvement of the above-described pathway in the aberrant differentiation direction of LR-MSCs under TGF-ß1 stimulation by overexpressing or knocking down key genes within the pathway. RESULTS: Our results revealed that METTL3-mediated m6A RNA methylation was significantly upregulated in both TGF-ß1-treated LR-MSCs and fibrotic mouse lung tissues. This process directly led to the aberrant differentiation of LR-MSCs into myofibroblasts by targeting the miR-21/PTEN pathway. Moreover, inhibition of METTL3 or miR-21 and overexpression of PTEN could rescue this abnormal differentiation. CONCLUSION: Our study demonstrated that m6A RNA methylation induced aberrant LR-MSC differentiation into myofibroblasts via the METTL3/miR-21/PTEN signaling pathway. We indicated a novel mechanism to promote PF progression. Targeting METTL3-mediated m6A RNA methylation and its downstream targets may present innovative therapeutic approaches for the prevention and treatment of PF.

Fan beam CT-guided online adaptive external radiotherapy of uterine cervical cancer: a dosimetric evaluation.

PURPOSE: To discuss the dosimetric advantages and reliability of the accurate delivery of online adaptive radiotherapy(online ART) for uterine cervical cancer(UCC). METHODS AND MATERIALS: Six UCC patients were enrolled in this study. 95% of the planning target volume (PTV) reached 100% of the prescription dose (50.4 Gy/28fractions/6weeks) was required. The patients were scanned with uRT-Linac 506c KV-FBCT then the target volume (TV) and organs at risk (OARs) were delineated by doctors. The dosimeters designed and obtained a routine plan (Plan0). KV-FBCT was used for image guidance before subsequent fractional treatment. The online ART was processed after registration, which acquired a virtual nonadaptive radiotherapy plan (VPlan) and an adaptive plan (APlan). VPlan was the direct calculation of Plan0 on the fractional image, while APlan required adaptive optimization and calculation. In vivo dose monitoring and three-dimensional dose reconstruction were required during the implementation of APlan. RESULTS: The inter-fractional volumes of the bladder and rectum changed greatly among the treatments. These changes influenced the primary gross tumor volume (GTVp) and the position deviation of GTVp and PTV and positively affected the prescription dose coverage of TV. GTVp decreased gradually along with dose accumulation. The Dmax, D98, D95, D50, and D2 of APlan were superior to those of VPlan in target dose distribution. APlan had good conformal index, homogeneity index and target coverage. The rectum V40 and Dmax, bladder V40, the small bowel V40 and Dmax of APlan were better than that of VPlan. The APlan's fractional mean γ passing rate was significantly higher than the international standard and the mean γ passing rate of all cases after the three-dimensional reconstruction was higher than 97.0%. CONCLUSION: Online ART in external radiotherapy of UCC significantly improved the dose distribution and can become an ideal technology to achieve individualized precise radiotherapy.

Safety of early cumulus cell removal combined with early rescue ICSI in the prevention of fertilization failure.

RESEARCH QUESTION: What are the clinical outcomes and safety implications of early cumulus cell removal after short-term insemination combined with early rescue intracytoplasmic sperm injection (ICSI) in preventing fertilization failure? DESIGN: In this retrospective study, a total of 14,360 cycles were divided into four groups based on insemination method and fertilization ability: conventional IVF group (n = 5519); early cumulus cell removal group (n = 4107); conventional ICSI group (n = 4215); and early rescue ICSI group (where failed or low fertilization was predicted, n = 519). Fertilization outcomes, pregnancy outcomes, neonatal outcomes and birth defects were analysed by comparing the early cumulus cell removal group with the conventional IVF group, and the early rescue ICSI group with the conventional ICSI group. RESULTS: There were no significant differences in the outcomes of fertilization, pregnancy, neonates or birth defects between the conventional IVF group and the early cumulus cell removal group (P > 0.05). When compared with the conventional ICSI group, the early rescue ICSI group had similar rates of two pronuclei (2PN) at fertilization, clinical pregnancy, miscarriage, ectopic pregnancy, live birth, sex, mean gestational age, very low birthweight, macrosomia and birth defects (P > 0.05) but a higher polyploidy rate, lower high-quality embryo rate (both P < 0.001), lower twin pregnancy rate (P < 0.01), lower rate of low birthweight, and a higher rate of normal birthweight (both P = 0.024). CONCLUSIONS: Early cumulus cell removal combined with early rescue ICSI led to good pregnancy and neonatal outcomes without an increase in birth defects. This approach could therefore be an effective and safe method for patients with fertilization failure in conventional IVF.

PD-L1 upregulation promotes drug-induced pulmonary fibrosis by inhibiting vimentin degradation.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and limited therapeutic options. The immune checkpoint PD1/PD-L1 axis is related to the pathogenesis of pulmonary fibrosis, and upregulated expression levels of PD-L1 have been demonstrated in IPF patients. However, the mechanism of PD-L1 in pulmonary fibrosis is not fully understood. Here, we demonstrated upregulated expression of PD-L1 in fibrotic lung tissues and sera of IPF patients. Bleomycin (BLM) treatment induced PD-L1 upregulation, EMT (Epithelial-Mesenchymal Transition) and fibrosis-like morphology changes in human pulmonary alveolar epithelial cells (HPAEpiCs). Silencing PD-L1 attenuated BLM-induced EMT and fibrosis-like morphology changes in HPAEpiCs. In addition, we identified that PD-L1 directly binds to vimentin and inhibits vimentin ubiquitination, thereby increasing vimentin levels in HPAEpiCs. Silencing of vimentin inhibited BLM- and PD-L1-induced fibrosis in HPAEpiCs. The correlation between PD-L1 and EMT or vimentin expression was further confirmed in clinical samples and animal models. Finally, we used BLM- and paraquat-induced pulmonary fibrosis animal models to confirm the anti-pulmonary fibrosis effects of PD-L1 silencing. Taken together, our findings suggest that upregulated PD-L1 stimulates EMT of alveolar epithelial cells by increasing vimentin levels by inhibiting vimentin ubiquitination, thereby contributing to pulmonary fibrosis.

NDV-induced autophagy enhances inflammation through NLRP3/Caspase-1 inflammasomes and the p38/MAPK pathway.

Newcastle disease (ND), caused by the Newcastle disease virus (NDV), is a highly virulent infectious disease of poultry. Virulent NDV can cause severe autophagy and inflammation in host cells. While studies have shown a mutual regulatory relationship between autophagy and inflammation, this relationship in NDV infection remains unclear. This study confirmed that NDV infection could trigger autophagy in DF-1 cells to promote cytopathic and viral replication. NDV-induced autophagy was positively correlated with the mRNA levels of inflammatory cytokines such as IL-1ß, IL-8, IL-18, CCL-5, and TNF-α, suggesting that NDV-induced autophagy promotes the expression of inflammatory cytokines. Further investigation demonstrated that NLRP3 protein expression, Caspase-1 activity, and p38 phosphorylation level positively correlated with autophagy, suggesting that NDV-induced autophagy could promote the expression of inflammatory cytokines through NLRP3/Caspase-1 inflammasomes and p38/MAPK pathway. In addition, NDV infection also triggered mitochondrial damage and mitophagy in DF-1 cells, but did not result in a large leakage of reactive oxygen species (ROS) and mitochondrial DNA (mtDNA), indicating that mitochondrial damage and mitophagy do not contribute to the inflammation response during NDV infection.

High diffraction efficiency varied-line-space concave gratings for the Lyman ultraviolet explorer.

In this paper we present the design and fabrication of the reflection varied-line-space concave grating (VLSCG) for the project of CAFE (the Census of warm-hot intergalactic medium, Accretion, and Feedback Explorer), which aims to detect and map the warm-hot circumgalactic medium via OVI emission at 103.2 nm and 103.8 nm, using two off-Rowland-circle spectrograph channels. High diffraction efficiency at LUV is supposed for the VLSCG and an aperture ratio as small as $F/3.6$ is desired for a compact design. The gratings are fabricated by holographic lithography and ion beam etching techniques. We introduce an additional lens into the normal holographic exposing system to generate the varied-line-space grating patterns. Grooves with triangle profiles are obtained to increase the diffraction efficiency by oblique ion beam bombardment during the etching process. Finally, several VLSCGs with a central line density of 3300 lines/mm have been fabricated successfully. The measured results show that the groove efficiency reaches 51% at 106.4 nm and 31% at 127.4 nm. We imitated the working optical path of the spectrometer and used the ${-}{1}$ order of the VLSCG to measure the image near the exit slit. The results showed that the image of the point source has a vertical extent of 0.68 mm, and the aberrations have been corrected.

Insight into autophagy in platinum resistance of cancer.

Platinum drugs, as a class of widely used chemotherapy agents, frequently appear in the treatment of cancer at different phrases. However, platinum resistance is the major bottleneck of platinum drugs for exerting anti-tumor effect. At present, the mechanism of platinum resistance has been thoroughly explored in terms of drug delivery methods, DNA damage repair function, etc., but it has not yet been translated into an effective weapon for reversing platinum resistance. Recently, autophagy has been proved to be closely related to platinum resistance, and the involved molecular mechanism may provide a new perspective on platinum resistance. The aim of this review is to sort out the studies related to autophagy and platinum resistance, and to focus on summarizing the relevant molecular mechanisms, so as to provide clues for future studies related to autophagy and platinum resistance.

Pathogen detection in suspected spinal infection: metagenomic next-generation sequencing versus culture.

PURPOSE: The aim is to compare the pathogen detection performance of metagenomic next-generation sequencing (mNGS) and the culturing of percutaneous needle biopsy samples obtained from an individual with a suspected spinal infection. METHODS: A retrospective study of 141 individuals with a suspected spinal infection was conducted, and mNGS was performed. The microbial spectra and detection performance between mNGS and the culturing-based method were compared, and the effects of antibiotic intervention and biopsy on the detection performance were assessed. RESULTS: The microorganisms isolated most commonly via the culturing-based method were Mycobacterium tuberculosis (n = 21), followed by Staphylococcus epidermidis (n = 13). The most common microorganisms detected via mNGS were Mycobacterium tuberculosis complex (MTBC) (n = 39), followed by Staphylococcus aureus (n = 15). The difference in the type of detected microorganisms between culturing and mNGS was observed only in Mycobacterium (P = 0.001). mNGS helped identify potential pathogens in 80.9% of cases, which was significantly higher than the positivity rate of 59.6% observed for the culturing-based method (P < 0.001). Moreover, mNGS had a sensitivity of 85.7% (95% CI, 78.4% to 91.3%), a specificity of 86.7% (95% CI, 59.5% to 98.3%), and sensitivity gains of 35% (85.7% vs. 50.8%; P < 0.001) during culturing, while no differences were observed in the specificity (86.7% vs. 93.3%; P = 0.543). In addition, antibiotic interventions significantly lowered the positivity rate of the culturing-based method (66.0% vs. 45.5%, P = 0.021) but had no effects on the results of mNGS (82.5% vs. 77.3%, P = 0.467). CONCLUSION: The use of mNGS could result in a higher detection rate compared to that observed with the culturing-based method in an individual with spinal infection and is particularly valuable for evaluating the effects of a mycobacterial infection or previous antibiotic intervention.

Effects of optimized nitrogen fertilizer management on the yield, nitrogen uptake, and ammonia volatilization of direct-seeded rice.

BACKGROUND: Direct-seeded rice has been developed rapidly because of labor savings. Changes in rice cultivation methods put forward new requirements for nitrogen (N) fertilizer management practices. Field experiments with five different fertilizer ratios of basal, tillering and panicle fertilizer, namely N1 (10:0:0), N2 (6:2:2), N3 (4:3:3), N4 (2:4:4) and N5 (0:5:5), were conducted to investigate the effects of different N fertilizer management practices on yield formation, N uptakes, and ammonia (NH3 ) volatilization from paddy fields in direct-seeded rice. RESULTS: The results showed that the N4 treatment improved grain yield by 5.1% while decreasing NH3 volatilization by 20.4% compared with that of conventional fertilizer treatment (N2). The panicle number per unit area was the key factor to determine the yield of direct-seeded rice (72%). Excessive N application of basal fertilizer (N1) reduced seedling emergence, N use efficiency, and yield by 45.3%, 160.6%, and 6.9% respectively and increased NH3 volatilization by 28.1% compared with that of the N4 treatment. Removal of basal N fertilizer (N5) N reduced spike number and yield by 13.0% and 6.9% respectively, minimizing NH3 volatilization while affecting the construction of high-yielding populations compared with that of the N4 treatment. CONCLUSION: Optimized N fertilizer management achieved delayed senescence (maintenance of higher leaf Soil Plant Analysis Development meter values in late reproduction), higher canopy photoassimilation (suitable leaf area), higher N fertilizer use efficiency, and less N loss (lower cumulative NH3 volatilization). © 2023 Society of Chemical Industry.