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Amino acid homeostasis is interconnected with the immune network of plants. During plant-pathogen interaction, amino acid transporters (AATs) have been shown to be involved in plant immune responses. However, the molecular mechanism by which how AATs function in this process remains elusive. In this study, we identify OsMP1 that acts as a quantitative trait locus against blast fungus from a joint analysis of GWAS and QTL mapping in rice. Heterogeneous expression of OsMP1 in yeast supports its function in transporting a wide range of amino acids, including Thr, Ser, Phe, His and Glu. OsMP1 could also mediate 15N-Glu efflux and influx in Xenopus oocyte cells. The expression of OsMP1 is dramatically induced by Magnaporthe oryzae in the resistant landrace Heikezijing, while remaining unresponsive in the susceptible landrace Suyunuo. Overexpressing OsMP1 in Suyunuo enhances disease resistance to blast fungus and leaf-blight bacterium without yield penalty. Furthermore, the overexpression of OsMP1 leads to increased accumulation of Thr, Ser, Phe and His in the leaves. And the heightened levels of these amino acids contribute to reduced disease susceptibility, which is associated with upregulated jasmonic acid pathway. Thus, our results elucidate the pivotal role of OsMP1 in disease resistance and provide a potential target for breeding more resistant rice cultivars without compromising yield., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Gibberellins (GAs) play crucial roles in regulating plant architecture and grain yield of crops. In rice, the inactivation of endogenous bioactive GAs and their precursors by GA 2-oxidases (GA2oxs) regulates stem elongation and reproductive development. However, the regulatory mechanisms of GA2ox gene expression, especially in rice reproductive organs, are unknown. The BEL1-like homeodomain protein OsBLH4, a negative regulatory factor for the rice OsGA2ox1 gene, was identified in this study. Loss of OsBLH4 function results in decreased bioactive GA levels and pleiotropic phenotypes, including reduced plant height, decreased grain number per panicle, and delayed heading date, as also observed in OsGA2ox1-overexpressing plants. Consistent with the mutant phenotype, OsBLH4 was predominantly expressed in shoots and young spikelets; its encoded protein was exclusively localized in the nucleus. Molecular analysis demonstrated that OsBLH4 directly bound to the promoter region of OsGA2ox1 to repress its expression. Genetic assays revealed that OsBLH4 acts upstream of OsGA2ox1 to control rice plant height, grain number, and heading date. Taken together, these results indicate a crucial role for OsBLH4 in regulating rice plant architecture and yield potential via regulation of bioactive GA levels, and provide a potential strategy for genetic improvements of rice., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Atmospheric sulfate aerosols contribute significantly to air pollution and climate change. Sulfate formation mechanisms during winter haze events in northern China have recently received considerable attention, with more than 10 studies published in high-impact journals. However, the conclusions from in-field measurements, laboratory studies, and numerical simulations are inconsistent and even contradictory. Here, we propose a physically based yet simple method to clarify the debate on the dominant sulfate formation pathway. Based on the hazes evolving in the synoptic scale, first, a characteristic sulfate formation rate is derived using the Eulerian mass conservation equation constrained by in situ observations. Then, this characteristic value is treated as a guideline to determine the dominant sulfate formation pathway with a 0D chemical box model. Our observation-derived results establish a linkage between studies from laboratory experiments and chemical transport model simulations. A convergent understanding could therefore be reached on sulfate formation mechanisms in China's wintertime haze. This method is universal and can be applied to various haze conditions and different secondary products., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Brassinosteroids (BRs) are a class of phytohormones that regulate plant growth and development. In previous studies, we cloned and identified PROTEIN PHOSPHATASE WITH KELCH-LIKE1 (OsPPKL1) as the causal gene for the quantitative trait locus GRAIN LENGTH3 (qGL3) in rice (Oryza sativa). We also showed that qGL3/OsPPKL1 is mainly located in the cytoplasm and nucleus and negatively regulates BR signaling and grain length. Because qGL3 is a negative regulator of BR signaling, its turnover is critical for rapid response to changes in BRs. Here, we demonstrate that qGL3 interacts with the WD40-domain-containing protein WD40-REPEAT PROTEIN48 (OsWDR48), which contains a nuclear export signal (NES). The NES signal is crucial for the cytosolic localization of OsWDR48 and also functions in the self-turnover of qGL3. We show that OsWDR48 physically interacts with and genetically acts through qGL3 to modulate BR signaling. Moreover, qGL3 may indirectly promote the phosphorylation of OsWDR48 at the Ser-379 and Ser-386 sites. Substitutions of both phosphorylation sites in OsWDR48 to non-phosphorylatable alanine enhanced the strength of the OsWDR48-qGL3 interaction. Furthermore, we found that brassinolide can promote the accumulation of non-phosphorylated OsWDR48, leading to strong interaction intensity between qGL3 and OsWDR48. Taken together, our results show that OsWDR48 facilitates qGL3 retention and induces degradation of qGL3 in the cytoplasm. These findings suggest that qGL3 self-modulates its turnover by binding to OsWDR48 to regulate its cytoplasmic localization and stability, leading to efficient orchestration of BR signal transduction in rice., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Apolipoprotein E (apoE) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Microglia exhibit a substantial upregulation of apoE in AD-associated circumstances, despite astrocytes being the primary source of apoE expression and secretion in the brain. Although the role of astrocytic apoE in the brain has been extensively investigated, it remains unclear that whether and how apoE particles generated from astrocytes and microglia differ in biological characteristic and function. Here, we demonstrate the differences in size between apoE particles generated from microglia and astrocytes. Microglial apoE particles impair neurite growth and synapses, and promote neuronal senescence, whereas depletion of GPNMB (glycoprotein non-metastatic melanoma protein B) in microglial apoE particles mitigated these deleterious effects. In addition, human APOE4-expressing microglia are more neurotoxic than APOE3-bearing microglia. For the first time, these results offer concrete evidence that apoE particles produced by microglia are involved in neuronal senescence and toxicity., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Long noncoding RNAs (lncRNAs) play a role in the emergence and progression of several human tumors, including luminal B breast cancer (BC). The biological functions and potential mechanisms of lncRNA myocardial infarction-associated transcripts (MIAT) in luminal B BC, on the contrary, are unknown. In this work, we used UALCAN database analysis to find high expression of lncRNA MIAT in luminal BC tissues and also confirmed high levels of lncRNA MIAT expression in luminal B BC tissues and cells. In vitro knockdown of MIAT inhibited the proliferation, migration, and invasion of BT474 cells. In addition, we found that miR-150-5p levels were significantly reduced in luminal B BC specimens and cells, and miR-150-5p levels were significantly increased when MIAT was knocked down. And TIMER database analysis showed that MIAT was positively associated with PDL1. Through bioinformatic tools and in vitro experiments, lncRNA MIAT could function as a competitive endogenous RNA (CeRNA) to further regulate programmed cell death ligand 1 (PDL1) expression by directly sponging miR-150-5p. In conclusion, our data suggest that MIAT, an oncogene, may sponge miR-150-5p to regulate PDL1 expression and affect proliferation, migration, and invasion in luminal B BC in vitro., (© 2023. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.)

Preharvest sprouting (PHS) is an undesirable trait that decreases yield and quality in rice production. Understanding the genes and regulatory mechanisms underlying PHS is of great significance for breeding PHS-resistant rice. In this study, we identified a mutant, preharvest sprouting 39 (phs39), that exhibited an obvious PHS phenotype in the field. MutMap + analysis and transgenic experiments demonstrated that OsAAH, which encodes allantoate amidohydrolase, is the causal gene of phs39 and is essential for PHS resistance. OsAAH was highly expressed in roots and leaves at the heading stage and gradually increased and then weakly declined in the seed developmental stage. OsAAH protein was localized to the endoplasmic reticulum, with a function of hydrolyzing allantoate in vitro. Disruption of OsAAH increased the levels of ureides (allantoate and allantoin) and activated the tricarboxylic acid (TCA) cycle, and thus increased energy levels in developing seeds. Additionally, the disruption of OsAAH significantly increased asparagine, arginine, and lysine levels, decreased tryptophan levels, and decreased levels of indole-3-acetic acid (IAA) and abscisic acid (ABA). Our findings revealed that the OsAAH of ureide catabolism is involved in the regulation of rice PHS via energy and hormone metabolisms, which will help to facilitate the breeding of rice PHS-resistant varieties., (© 2024. The Author(s).)

The hydroxyl radical (OH), as the central atmospheric oxidant, controls the removal rates of methane, a powerful greenhouse gas. It is being suggested that OH levels would decrease with reductions of nitrogen oxides and ozone levels by climate polices, but this remains unsettled. Here, we show that driven by the carbon neutrality pledge, the global-mean OH concentration, derived from multiple chemistry-climate model simulations, is projected to be significantly increasing with a trend of 0.071‒0.16% per year during 2015-2100. The leading cause of this OH enhancement is dramatic decreases in carbon monoxide and methane concentrations, which together reduce OH sinks. The OH increase shortens methane's lifetime by 0.19‒1.1 years across models and subsequently diminishes methane's radiative forcing. If following a largely unmitigated scenario, the global OH exhibits a significant decrease that would exacerbate methane's radiative forcing. Thus, we highlight that targeted emission abatement strategies for sustained oxidation capacity can benefit climate change mitigation in the Anthropocene., (© 2024. The Author(s).)

Soil salinity has a major impact on rice seed germination, severely limiting rice production. Herein, a rice germination defective mutant under salt stress (gdss) was identified by using chemical mutagenesis. The GDSS gene was detected via MutMap and shown to encode potassium transporter OsHAK9. Phenotypic analysis of complementation and mutant lines demonstrated that OsHAK9 was an essential regulator responsible for seed germination under salt stress. OsHAK9 is highly expressed in germinating seed embryos. Ion contents and non-invasive micro-test technology results showed that OsHAK9 restricted K + efflux in salt-exposed germinating seeds for the balance of K + /Na + . Disruption of OsHAK9 significantly reduced gibberellin 4 (GA 4 ) levels, and the germination defective phenotype of oshak9a was partly rescued by exogenous GA 3 treatment under salt stress. RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction analysis demonstrated that the disruption of OsHAK9 improved the GA-deactivated gene OsGA2ox7 expression in germinating seeds under salt stress, and the expression of OsGA2ox7 was significantly inhibited by salt stress. Null mutants of OsGA2ox7 created using clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 approach displayed a dramatically increased seed germination ability under salt stress. Overall, our results highlight that OsHAK9 regulates seed germination performance under salt stress involving preventing GA degradation by mediating OsGA2ox7, which provides a novel clue about the relationship between GA and OsHAKs in rice., (© 2024 The Authors. Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Staphylococcus aureus (S. aureus) is a prevalent foodborne pathogen that could cause severe food poisoning. Thus, rapid, efficient, and ultrasensitive detection of S. aureus in food samples is urgently needed. Here, we report an efficient magnetic enrichment cascade single-step recombinase polymerase amplification (RPA)-CRISPR/Cas12a assay for the ultrasensitive detection of S. aureus. Magnetic beads (MBs) functionalized with S. aureus-specific antibodies were initially used for S. aureus enrichment from the complex matrix, with 98% capture efficiency in 5 min and 100-fold sensitivity improvement compared with unenriched S. aureus. Next, a single-step RPA-CRISPR/Cas12a-based diagnostic system with optimized extraction-free bacteria lysis was constructed. This assay could detect as low as 1 copy/μL (five copies/reaction) of extracted DNA template and 10 CFU/mL of S. aureus within 40 min. Furthermore, the assay could effectively detect S. aureus in real food samples such as lake water, orange juice, pork, and lettuce, with concordant results to qPCR assays. The proposed cascade signal-amplification assay eliminates the need for lengthy bacterial culture and complex sample preparation steps. Hence, the proposed assay shows great application potential for rapid, efficient, and ultrasensitive detection of pathogens in real food samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rice blast is one of the most devastating diseases, causing a significant reduction in global rice production. Developing and utilizing resistant varieties has proven to be the most efficient and cost-effective approach to control blasts. However, due to environmental pressure and intense pathogenic selection, resistance has rapidly broken down, and more durable resistance genes are being discovered. In this paper, a novel wall-associated kinase (WAK) gene, Pb4 , which confers resistance to rice blast, was identified through a genome-wide association study (GWAS) utilizing 249 rice accessions. Pb4 comprises an N-terminal signal peptide, extracellular GUB domain, EGF domain, EGF-Ca 2+ domain, and intracellular Ser/Thr protein kinase domain. The extracellular domain (GUB domain, EGF domain, and EGF-Ca 2+ domain) of Pb4 can interact with the extracellular domain of CEBiP. Additionally, its expression is induced by chitin and polygalacturonic acid. Furthermore, transgenic plants overexpressing Pb4 enhance resistance to rice blast. In summary, this study identified a novel rice blast-resistant gene, Pb4 , and provides a theoretical basis for understanding the role of WAKs in mediating rice resistance against rice blast disease.

Accumulating experimental data have shown that endogenous hormones play important roles in regulating seed dormancy and germination. Zanthoxylum nitidum is a medicinal plant that propagates via seeds, which require a long dormancy period for normal germination, and complex changes in metabolites occur during the germination process. However, the regulatory network of endogenous hormones and metabolites during the germination of Z. nitidum seeds remains unclear. This study investigated the dynamic changes in the levels of metabolites and endogenous hormones during the germination of Z. nitidum seeds. The results revealed an increase in the levels of gibberellin 3 (GA 3 ), 12-oxophytodienoic acid (OPDA), 1-aminocyclopropane-1-carboxylic acid (ACC) and trans-zeatin (TZ) and decrease in the levels of abscisic acid (ABA), jasmonic acid (JA), N -[(-)-jasmonoyl]-(S)-isoleucine (JA-Ile) and trans-zeatin riboside (TZR). Overall, 112 differential metabolites (DAMs) were screened from 3 seed samples (Sa, Sb and Sc), most of which are related to primary metabolism. A total of 16 DAMs (including 3 monosaccharides, 3 phosphate lipids, 3 carboxylic acids, 1 amino acid, 2 pyrimidines, and 4 nucleotides) were identified in the three sample comparison pairs (Sa vs Sb, Sa vs Sc, and Sb vs Sc); these DAMs were significantly enriched in purine metabolism; glycerophospholipid metabolism, citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism and pyruvate metabolism. OPDA, ACC and GAs were significantly positively correlated with upregulated metabolites, whereas ABA and JA were significantly positively correlated with downregulated metabolites. Finally, a hypothetical metabolic network of endogenous hormones that regulate seed germination was constructed. This study deepens our understanding of the importance of endogenous hormonal profiles that mediate seed germination.

A 71-year-old male patient presented to our emergency department with a 1-day history of abdominal pain after an accidental fall. Laboratory test results were as follows: a white blood cell count of 2.32 × 109/L, blood lactate of 3.0 mmol/L, pH 7.30, calcitonin precursor level of 71.09 ng/ml, and creatinine of 115 umol/L. The abdominal CT revealed: portal vein gas accumulation (PVGA) accompanied by a fluid-air level; pneumatosis cystoides intestinalis (PCI) manifested as multiple gas collections within the wall of the lower small intestine. Based on lowered blood pH and elevated lactate levels, there was a high suspicion of small intestinal ischemic necrosis. Subsequent emergency laparotomy and pathological examination confirmed necrosis of the small intestine.

Summary: In recent years, phased small interfering RNA has been found to play crucial roles in many biological processes in plants. However, efficiently predicting phasiRNA regulatory cascades with computational methods is still challenging. Here, we introduce PhasiHunter, a phasiRNA regulatory network prediction tool that has several distinctive features compared to existing tools: (i) PhasiHunter employs two major phasiRNA prediction algorithms, namely phase score and hypergeometric distribution-based methods, to ensure the integrity and accuracy of prediction; (ii) PhasiHunter can identify phasiRNAs and their regulatory networks based on multiple reference sequences and the predicted results can be automatically integrated; (iii) PhasiHunter can efficiently identify the phasiRNAs generated through alternative splicing events; and (iv) the excellent data structure and parallel computing architecture allow PhasiHunter to predict phasiRNAs and their regulatory pathways with high efficiency., Availability and Implementation: PhasiHunter is an open-source tool that is available at https://github.com/HuangLab-CBI/PhasiHunter., (© The Author(s) 2023. Published by Oxford University Press.)

Aims: Despite shared pathophysiological mechanisms, patients with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) have a poorer prognosis than those with PAH after congenital heart defect repair. Ventricular adaption remains unclear and could provide a basis for explaining differences in clinical outcomes. The aim of this prospective study was to assess clinical status, haemodynamic profile, and biventricular adaptation to PAH in children with various forms of PAH., Methods and Results: Consecutive patients with IPAH/HPAH or post-operative PAH were prospectively recruited (n = 64). All patients underwent a comprehensive, protocolized assessment including functional assessment, measurement of brain natriuretic peptide (BNP) levels, invasive measurements, and a cardiac magnetic resonance (CMR) assessment. A cohort of age- and sex-matched healthy subjects served as controls. Patients with post-operative PAH had a better functional class (61.5 vs. 26.3% in Class I/II, P = 0.02) and a longer 6-min walk distance (320 ± 193 vs. 239 ± 156 m, P = 0.008) than IPAH/HPAH. While haemodynamic parameters were not significantly different between IPAH/HPAH and post-operative patients, post-operative patients with PAH presented with higher left ventricular volumes and better right ventricular function compared with patients with IPAH/HPAH (P < 0.05). On correlation analyses, left ventricular volumetric parameters were highly correlated with BNP and 6-min walk test distance in this population., Conclusion: Despite comparable haemodynamic profiles, patients with post-operative PAH had less functional limitation than their IPAH/HPAH counterparts. This is potentially related to the differential biventricular adaptation pattern evident on CMR with better myocardial contractility and higher left ventricular volumes in post-operative patients with PAH, highlighting the importance of ventriculo-ventricular interaction in the setting of PAH., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The diagnostic efficacy of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) is limited in breast cancer (BC), highlighting the necessity of exploring novel biomarkers to improve for BC diagnosis. Therefore, we assessed the diagnostic value of fat mass and obesity-associated protein (FTO), phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit β (PIK3CB) as a potential complementary biomarker to CEA and CA153 in breast cancer by measuring serum FTO,PIK3CB levels. FTO, PIK3CB, CEA and CA15-3 levels were measured in 112 BC patients and 64 healthy controls using enzyme-linked immunosorbent assay or electrochemiluminescence immunoassay. Spearman's rank correlation analysis was conducted to assess the correlation between the levels of the 2 markers. The relationships between FTO, PIK3CB, CEA, CA15-3 and clinical characteristics were evaluated. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic value of FTO, PIK3CB, CEA and CA15-3 of BC. Serum FTO, PIK3CB, CEA and CA15-3 levels were significantly increased in BC. There was no correlation between FTO, PIK3CB and CEA, CA15-3. FTO and PIK3CB demonstrated significant diagnostic performance for breast cancer, with FTO achieving a specificity of 90.63%. The diagnostic performance of 2-four biomarker combinations was significantly superior to individual CEA or CA153, with a combined panel of 4 biomarkers yielding an area under the curve (AUC) of 0.918, sensitivity of 81.25% and specificity of 85.94%. In early-stage breast cancer (I + II), the combination of FTO, PIK3CB, CEA and CA153 yielded an AUC of 0.895, sensitivity of 77.22% and specificity of 85.71%. FTO and PIK3CB can be served as potential biomarkers to complement CEA and CA15-3 for BC diagnosis. Combining FTO, PIK3CB, CEA and CA15-3 improves the diagnostic efficiency of breast cancer., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The characteristics of turbulent CO 2 transport and its dissimilarity with heat and water vapor are investigated over both natural and urban areas. A novel index TS is proposed to effectively quantify the transport similarity between two scalars. By comparison, it is found that the transport of CO 2 shows great complexity in urban areas. It is ideal in natural areas that heat, water vapor, and CO 2 are efficiently transported by thermal plumes (i.e., the dominant coherent structures under unstable conditions), and that the transport similarity among them becomes increasingly evident with the increase of atmospheric instability. However, in urban areas, the transport of CO 2 shows significant dissimilarity from that of heat and water vapor, and it is hard to detect the role of thermal plumes. Furthermore, it is observed that the sector-average CO 2 flux in urban areas changes largely with the wind blowing from different urban functional areas. Specially, for a given direction, there might be contrasting characteristics in CO 2 transport under different unstable conditions. These features can be explained by the flux footprint. Since the CO 2 sources and sinks are distributed heterogeneously in urban areas, the variation of footprint areas with wind direction or atmospheric instability, causes the alternation between source-dominated (i.e., upward) and sink-dominated (i.e., downward) CO 2 transport. Therefore, the role of coherent structures in CO 2 transport is substantially confused by spatially-confined sources/sinks in urban areas, leading to significant transport dissimilarity between CO 2 and heat or water vapor and thus the great complexity in CO 2 transport. The findings in this study are helpful to promote the understanding of the global carbon cycle in depth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Pulmonary hypertension (PH) is a fatal disease caused by progressive pulmonary vascular remodeling (PVR). Currently, the mechanisms underlying the occurrence and progression of PVR remain unclear, and effective therapeutic approaches to reverse PVR and PH are lacking. Since the beginning of the 21st century, the endogenous sulfur dioxide (SO 2 )/aspartate transaminase system has emerged as a novel research focus in the fields of PH and PVR. As a gaseous signaling molecule, SO 2 metabolism is tightly regulated in the pulmonary vasculature and is associated with the development of PH as it is involved in the regulation of pathological and physiological activities, such as pulmonary vascular cellular inflammation, proliferation and collagen metabolism, to exert a protective effect against PH. In this review, we present an overview of the studies conducted to date that have provided a theoretical basis for the development of SO 2 -related drug to inhibit or reverse PVR and effectively treat PH-related diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhou, Zhang, Jin and He.)

Breast cancer is characterized by a high incidence rate and its treatment challenges, particularly in certain subtypes. Consequently, there is an urgent need for the development of novel therapeutic approaches. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) is currently gaining momentum for the treatment of breast cancer. Substantial progress has been made in clinical studies employing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors for breast cancer, but the cure rates are relatively low. To improve the efficacy of CTLA-4-based therapy for breast cancer, further research is imperative to explore more effective immune-based treatment strategies. In addition to monotherapy, CTLA-4 inhibitors are also being investigated in combination with other ICIs or alternative medications. However, it should be noted that immune-based treatments may cause adverse events. This review focuses on the mechanisms of CTLA-4 inhibitor monotherapy or combination therapy in breast cancer. We systematically summarize the latest research and clinical advances in CTLA-4-based immunotherapy for breast cancer, providing new perspectives on the treatment of breast cancer. In addition, this review highlights the immune-related adverse events (irAEs) associated with CTLA-4 inhibitors, providing insights into the development of appropriate clinical tumor immunotherapy regimens and intervention strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Mi, Xin, Cao, Song, Zhang and Yuan.)

Trehalose may improve plant stress tolerance by regulating gene expression under different abiotic stresses. DNA methylation is involved in plant growth and development, but also in response to abiotic stresses. 5-azacytidine is a widely used inhibitor of DNA methylation. In this study, tomato (Solanum lycopersicum L. 'Ailsa Craig') was used as experimental material to explore the effects of trehalose and DNA methylation on the growth and development in tomato seedlings under salt stress. 10 mM trehalose, 50 μM 5-azacytidine, and their combined treatments could significantly increase growth parameters in tomato under salt stress, indicating trehalose and 5-azacytidine might play crucial roles in alleviating salt stress both synergistically and independently. Additionally, trehalose significantly down-regulated the expression of DNA methylase genes (SlDRM5, SlDRM1L1, SlCMT3 and SlCMT2) and up-regulated the expression of DNA demethylases genes under salt stress, suggesting that trehalose might regulate DNA methylation under salt stress condition. Under salt stress, trehalose and 5-azacytidine treatments enhanced antioxidant enzyme activity and induced antioxidant enzyme gene expression in tomato seedlings. Meanwhile, trehalose and 5-azacytidine increased ABA content by regulating the expression of ABA metabolism-related genes, thereby enhancing salt tolerance in tomato. Altogether, these results suggest that trehalose conferred salt tolerance in tomato seedlings probably by DNA demethylation and enhancing antioxidant capability and ABA accumulation., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Brassinosteroids (BRs) are a class of polyhydroxylated steroidal phytohormones that are essential for plant growth and development. Rice BRASSINOSTEROID-INSENSITIVE1 (BRI1)-ASSOCIATED RECEPTOR KINASES (OsBAKs) are plasma membrane-localized receptor kinases belonging to the subfamily of leucine-rich repeat receptor kinases. It has been found that in Arabidopsis, BRs induce the formation of a BRI1-BAK1 heterodimer complex and transmit the cascade signal to BRASSINAZOLE RESISTANT1/bri1-EMS-SUPPRESSOR1 (BZR1/BES1) to regulate BR signaling. Here, in rice (Oryza sativa ssp. japonica), we found that OsBZR1 binds directly to the promoter of OsBAK2, but not OsBAK1, and represses the expression of OsBAK2 to form a BR feedback inhibition loop. Additionally, the phosphorylation of OsBZR1 by OsGSK3 reduced its binding to the OsBAK2 promoter. The osbak2 mutant displays a typical BR-deficiency phenotype and negative modulates the accumulation of OsBZR1. Interestingly, the grain length of the osbak2 mutant was increased whereas in the cr-osbak2/cr-osbzr1 double mutant, the reduced grain length of the cr-osbzr1 mutant was restored, implying that the increased grain length of osbak2 may be due to the rice somatic embryogenesis receptor kinase-dependent pathway. Our study reveals a novel mechanism by which OsBAK2 and OsBZR1 engage in a negative feedback loop to maintain rice BR homeostasis, facilitating a deeper understanding of the BR signaling network and grain length regulation in rice., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1310/coif). The authors have no conflicts of interest to declare.

Talaromyces purpurogenus , an endophytic fungus, exhibits beneficial effects on plants during plant-fungus interactions. However, the molecular mechanisms underlying plants' responses to T. purpurogenus under low-phosphorous (P) stress are not fully understood. In this study, we investigated the transcriptomic changes in maize with low-P-sensitive (31778) and -tolerant (CCM454) genotypes under low-P stress and its symbiotic interaction with T. purpurogenus . Its colonization enhanced plant growth and facilitated P uptake, particularly in 31778. Transcriptome sequencing revealed that 135 DEGs from CCM454 and 389 from 31778 were identified, and that only 6 DEGs were common. This suggested that CCM454 and 31778 exhibited distinct molecular responses to T. purpurogenus inoculation. GO and KEGG analysis revealed that DEGs in 31778 were associated with nicotianamine biosynthesis, organic acid metabolic process, inorganic anion transport, biosynthesis of various secondary metabolites and nitrogen metabolism. In CCM454, DEGs were associated with anthocyanin biosynthesis, diterpenoid biosynthesis and metabolic process. After T. purpurogenus inoculation, the genes associated with phosphate transporter, phosphatase, peroxidase and high-affinity nitrate transporter were upregulated in 31778, whereas AP2-EREBP-transcription factors were detected at significantly higher levels in CCM454. This study provided insights on the molecular mechanisms underlying plant-endophytic fungus symbiosis and low-P stress in maize with low-P-sensitive and -tolerant genotypes.

The Intelligent Earth (iEarth) framework, composed of four major themes: iEarth data, science, analytics, and decision, is proposed to define and build an interdisciplinary and synergistic framework for research, practice, and education that simultaneously safeguards the sustainable development of our living planet., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

A thin Silicon-On-Insulator (SOI) LDMOS with ultralow Specific On-Resistance ( R on,sp ) is proposed, and the physical mechanism is investigated by Sentaurus. It features a FIN gate and an extended superjunction trench gate to obtain a Bulk Electron Accumulation (BEA) effect. The BEA consists of two p-regions and two integrated back-to-back diodes, then the gate potential V GS is extended through the whole p-region. Additionally, the gate oxide W oxide is inserted between the extended superjunction trench gate and N-drift. In the on-state, the 3D electron channel is produced at the P-well by the FIN gate, and the high-density electron accumulation layer formed in the drift region surface provides an extremely low-resistance current path, which dramatically decreases the R on,sp and eases the dependence of R on,sp on the drift doping concentration ( N drift ). In the off-state, the two p-regions and N-drift deplete from each other through the gate oxide W oxide like the conventional SJ. Meanwhile, the Extended Drain (ED) increases the interface charge and reduces the R on,sp . The 3D simulation results show that the BV and R on,sp are 314 V and 1.84 mΩ∙cm -2 , respectively. Consequently, the FOM is high, reaching up to 53.49 MW/cm 2 , which breaks through the silicon limit of the RESURF.

Key Message: Two causal OsTTL and OsSAPK1 genes of the key locus qNL3.1 significantly associated with seed germination under salt stress were identified via a genome-wide association study, which could improve rice seed germination under salt stress. Rice is a salt-sensitive crop, and its seed germination determines subsequent seedling establishment and yields. In this study, 168 accessions were investigated for the genetic control of seed germination under salt stress based on the germination rate (GR), germination index (GI), time at which 50% germination was achieved (T 50 ) and mean level (ML). Extensive natural variation in seed germination was observed among accessions under salt stress. Correlation analysis showed significantly positive correlations among GR, GI and ML and a negative correlation with T 50 during seed germination under salt stress. Forty-nine loci significantly associated with seed germination under salt stress were identified, and seven of these were identified in both years. By comparison, 16 loci were colocated with the previous QTLs, and the remaining 33 loci might be novel. qNL3.1, colocated with qLTG-3, was simultaneously identified with the four indices in two years and might be a key locus for seed germination under salt stress. Analysis of candidate genes showed that two genes, the similar to transthyretin-like protein OsTTL and the serine/threonine protein kinase OsSAPK1, were the causal genes of qNL3.1. Germination tests indicated that both Osttl and Ossapk1 mutants significantly reduced seed germination under salt stress compared to the wild type. Haplotype analysis showed that Hap.1 of OsTTL and Hap.1 of OsSAPK1 genes were excellent alleles, and their combination resulted in high seed germination under salt stress. Eight accessions with elite performance of seed germination under salt stress were identified, which could improve rice seed germination under salt stress., (© 2023. The Author(s).)

A novel Cu-assisted photoelectron-chemical etching is proposed to fabricate GaN nanowires. The functional mechanism of assisted metals, etchant concentrations, and the addition of H 2 O 2 was investigated based on theoretical analysis and experiments. The low-cost metal-assisted etchant (CuSO 4 ) proved more favorable than the conventional noble one (AgNO 3 ) for the preparation of GaN nanowires in this work. The formed Ag dendrite blocked the etching when adopting the Ag-assisted etchant, while the Cu-assisted one did not. Moreover, the etchant consisting of 0.01 M CuSO 4 and 5 M HF was demonstrated to realize a relatively good surface morphology and fast etching rate. In addition, the common oxidant H 2 O 2 introduced a quasi-stable configuration between the Cu deposition and dissolution, slowing down the formation of the GaN nanowires. The proposed Cu-assisted photoelectron-chemical etching with the advantages of low cost, room temperature, and controllability could offer a new way to fabricate GaN nano-devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Wheat coleoptile is a sheath-like structure that helps to deliver the first leaf from embryo to the soil surface. Here, a RIL population consisting of 245 lines derived from Zhou 8425B × Chinese Spring cross was genotyped by the high-density Illumina iSelect 90K assay for coleoptile length (CL) QTL mapping. Three QTL for CL were mapped on chromosomes 2BL, 4BS and 4DS. Of them, two major QTL QCL.qau-4BS and QCL.qau-4DS were detected, which could explain 9.1%-22.2% of the phenotypic variances across environments on Rht-B1 and Rht-D1 loci, respectively. Several studies have reported that Rht-B1b may reduce the length of wheat CL but no study has been carried out at molecular level. In order to verify that the Rht-B1 gene is the functional gene for the 4B QTL, an overexpression line Rht-B1b -OE and a CRISPR/SpCas9 line Rht-B1b -KO were studied. The results showed that Rht-B1b overexpression could reduce the CL, while loss-of-function of Rht-B1b would increase the CL relative to that of the null transgenic plants (TNL). To dissect the underlying regulatory mechanism of Rht-B1b on CL, comparative RNA-Seq was conducted between Rht-B1b -OE and TNL. Transcriptome profiles revealed a few key pathways involving the function of Rht-B1b in coleoptile development, including phytohormones, circadian rhythm and starch and sucrose metabolism. Our findings may facilitate wheat breeding for longer coleoptiles to improve seedling early vigor for better penetration through the soil crust in arid regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Hao, Yang, Lv, Qin, Wang, Jia, Liu, Dai, Zeng, Zhang, He, Xia, Cao and Ma.)

Dopamine (DA) neurons in the ventral tegmental area (VTA) are critical to coping with stress. However, molecular mechanisms regulating their activity and stress-induced depression were not well understood. We found that the receptor tyrosine kinase ErbB4 in VTA was activated in stress-susceptible mice. Deleting ErbB4 in VTA or in DA neurons, or chemical genetic inhibition of ErbB4 kinase activity in VTA suppressed the development of chronic social defeat stress (CSDS)-induced depression-like behaviors. ErbB4 activation required the expression of NRG1 in the laterodorsal tegmentum (LDTg); LDTg-specific deletion of NRG1 inhibited depression-like behaviors. NRG1 and ErbB4 suppressed potassium currents of VTA DA neurons and increased their firing activity. Finally, we showed that acute inhibition of ErbB4 after stress attenuated DA neuron hyperactivity and expression of depression-like behaviors. Together, these observations demonstrate a critical role of NRG1-ErbB4 signaling in regulating depression-like behaviors and identify an unexpected mechanism by which the LDTg-VTA circuit regulates the activity of DA neurons., (© 2021. The Author(s).)

Hydrogen gas (H 2 ) is an important molecular messenger in animal and plant cells and is involved in various aspects of plant processes, including root organogenesis induction, stress tolerance and postharvest senescence. This study investigated the effect of H 2 fumigation on the quality of Lanzhou lily scales. The results indicated the H 2 remarkably declined the color variation and browning degree in Lanzhou lily scales by suppressing the activity of phenylalanine ammonia-lyase (PAL), peroxidase (POD) and polyphenol oxidase (PPO). Moreover, H 2 significantly alleviated the degradation of soluble proteins and soluble sugars in Lanzhou lily scales during postharvest storage, mitigating the decline in nutritional quality. This alleviating effect of H 2 might be achieved by increasing the endogenous H 2 concentration. Collectively, our data provide new insights into the postharvest quality reduction of Lanzhou lily scales mitigated by H 2 fumigation.

Proprioception is sensed by muscle spindles for precise locomotion and body posture. Unlike the neuromuscular junction (NMJ) for muscle contraction which has been well studied, mechanisms of spindle formation are not well understood. Here we show that sensory nerve terminals are disrupted by the mutation of Lrp4, a gene required for NMJ formation; inducible knockout of Lrp4 in adult mice impairs sensory synapses and movement coordination, suggesting that LRP4 is required for spindle formation and maintenance. LRP4 is critical to the expression of Egr3 during development; in adult mice, it interacts in trans with APP and APLP2 on sensory terminals. Finally, spindle sensory endings and function are impaired in aged mice, deficits that could be diminished by LRP4 expression. These observations uncovered LRP4 as an unexpected regulator of muscle spindle formation and maintenance in adult and aged animals and shed light on potential pathological mechanisms of abnormal muscle proprioception., (© 2023. The Author(s).)

Variation of the turbulence barrier effect caused by the turbulence intermittency have a strong impact on the vertical distribution and variation of pollutants, which limits the accuracy of pollution process simulation. Turbulence observation data from the five layers of the 255 m meteorological tower in Tianjin during two severe haze pollution periods were used to discuss energy changes during the enhancement and break of the turbulence barrier. Results showed that a sharp decrease in turbulence kinetic energy contributed to barrier enhancement and the kinetic energy transfer from sub-mesoscale motion to turbulence triggered the barrier break. The barrier break point tends to occur after Δ KE < 0 (the kinetic energy difference between turbulence and sub-mesoscale motion), subsequently followed by a significant increase in Δ KE. Due to the significant reduction in wind speed during severe haze pollution, type-B intermittency events occurred more frequently and existed at five heights. Type-A intermittency events were more likely to occur at the heights of 40 and 80 m, and type-C intermittency events were more likely to occur at heights above 80 m. Wind speed thresholds at different heights (2.5 m s -1 for 40 m, 4 m s -1 for 80 m, 4 m s -1 for 120 m, 4 m s -1 for 160 m, 4.5 m s -1 for 200 m) can be used to determine whether turbulent barrier effects occurred. This study provides an important research basis for solving the theoretical problem of the stable boundary layer that currently limits the accurate prediction of severe haze pollution processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Methane (CH 4 ) and brassinosteroids (BRs) are important signaling molecules involved in a variety of biological processes in plants., Results: Here, marigold (Tagetes erecta L. 'Marvel') was used to investigate the role and relationship between CH 4 and BRs during adventitious root (AR) formation. The results showed a dose-dependent effect of CH 4 and BRs on rooting, with the greatest biological effects of methane-rich water (MRW, CH 4 donor) and 2,4-epibrassinolide (EBL) at 20% and 1 μmol L - 1 , respectively. The positive effect of MRW on AR formation was blocked by brassinoazole (Brz, a synthetic inhibitor of EBL), indicating that BRs might be involved in MRW-regulated AR formation. MRW promoted EBL accumulation during rooting by up-regulating the content of campestanol (CN), cathasterone (CT), and castasterone (CS) and the activity of Steroid 5α-reductase (DET2), 22α-hydroxylase (DWF4), and BR-6-oxidase (BR6ox), indicating that CH 4 could induce endogenous brassinolide (BR) production during rooting. Further results showed that MRW and EBL significantly down-regulated the content of cellulose, hemicellulose and lignin during rooting and significantly up-regulated the hydrolase activity, i.e. cmcase, xylanase and laccase. In addition, MRW and EBL also significantly promoted the activity of two major cell wall relaxing factors, xyloglucan endotransglucosylase/hydrolase (XTH) and peroxidase, which in turn promoted AR formation. While, Brz inhibited the role of MRW on these substances., Conclusions: BR might be involved in CH 4 -promoted AR formation by increasing cell wall relaxation., (© 2022. The Author(s).)

Background: Paediatric-onset idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) is partially linked to genetic factors that may also affect treatment response and outcome. The relation between clinical characteristics and pathogenicity of gene variants in childhood IPAH/HPAH is still not well understood., Methods: We retrospectively analyzed IPAH/HPAH paediatric patients aged between 3 months and 18 years under follow-up at a large tertiary referral center. Whole-exome sequencing focused on PAH high-risk genes was performed in all patients. Pathogenicity grading of gene variant sites was assessed using ClinVar and population frequencies. The association between gene variants and death was studied using Cox proportional multivariate models., Results: Overall, 129 patients (54.3% females; 91.5% on PAH therapy) with a median age at diagnosis of 6.8 (IQR 3.4-10.7) years were included. A relevant PAH gene variant was detected in 95 patients (73.6%). The most common variants were in the BMPR2 ( n = 43, 3%) gene. Over a median follow-up period of 27.6 months, 26 children died. The presence of a likely pathogenic genetic variant was significantly associated with survival (HR: 3.56, p = 0.005) on multivariable Cox analysis. The number of PAH-specific drugs at presentation was associated with better survival in the cohort with pathogenic variants ( p = 0.02)., Conclusions: Pathogenic/likely pathogenic genetic variants are prevalent in children with PAH and are related to a worse prognosis irrespective of other recognized risk factors in this population. Combination PAH therapy was associated with superior prognosis in children with pathogenic variants or BMPR2 variants. Therefore, proactive medical therapy should be employed in this population.

Rice blast is a worldwide fungal disease that seriously affects the yield and quality of rice. Identification of resistance genes against rice blast disease is one of the effective ways to control this disease. However, panicle blast resistance genes, which are useful in the fields, have rarely been studied due to the difficulty in phenotypic identification and the environmental influences. Here, panicle blast resistance-3 ( Pb3 ) was identified by a genome-wide association study (GWAS) based on the panicle blast resistance phenotypes of 230 Rice Diversity Panel I (RDP-I) accessions with 700,000 single-nucleotide polymorphism (SNP) markers. A total of 16 panicle blast resistance loci (PBRLs) within three years including one repeated locus PBRL3 located in chromosome 11 were identified. In addition, 7 genes in PBRL3 were identified as candidate genes by haplotype analysis, which showed significant differences between resistant and susceptible varieties. Among them, one nucleotide-binding domain and Leucine-rich Repeat (NLR) gene Pb3 was highly conserved in multiple resistant rice cultivars, and its expression was significantly induced after rice blast inoculation. Evolutionary analysis showed that Pb3 was a typical disease resistance gene containing coiled-coil, NB-ARC, and LRR domains. T-DNA insertion mutants and CRISPR lines of Pb3 showed significantly reduced panicle blast resistance. These results indicate that Pb3 is a panicle blast resistance gene and GWAS is a rapid method for identifying panicle blast resistance in rice.

During heavy haze episodes, especially the cumulative stage (CS) of pollutants, strong turbulence intermittency and the resulting turbulence barrier effect (i.e., a phenomenon that turbulence at certain heights may disappear forming a laminar flow as if there is a barrier layer impeding the vertical turbulent exchange) suppress the vertical diffusion of pollutants, leading to high PM 2.5 concentrations. However, there are still some short-time removal processes of pollutants occurring at different heights in the CS, accompanied with interesting non-simultaneous drop or opposite variation of PM 2.5 concentrations at different heights. The ubiquitous internal gravity waves (IGWs) in the stable boundary layer (SBL) may play a critical role in the above situation, as they are closely related to the intermittent turbulence bursts appearing in the persistent weak turbulent motions. In this study, two representative heavy haze pollution cases were chosen to demonstrate the above speculation using five layers of turbulence data, two layers of pressure fluctuations and three layers of PM 2.5 concentrations. Results showed that the non-simultaneous drop or opposite variation of PM 2.5 concentrations was associated with the destruction of turbulence barrier by the vertical propagation of IGWs. IGWs generated by some certain mechanisms, such as nonhomogeneous terrain and wind shear around the low-level jet (LLJ), can propagate upward or downward with the upward or downward development of the temperature inversion layer. The vertically propagating IGWs then triggered intermittent increasing turbulence layer by layer. Turbulence between layers reconnected sequentially and turbulence barriers were broken in turn. The enhanced turbulent exchange expedited the pollutant diffusion, thus the PM 2.5 concentrations at different heights varied non-simultaneously even inversely. This study provides a good explanation for the positive effects of sub-mesoscale motions such as IGWs on triggering intermittent increasing turbulence and facilitating the diffusion of pollutants during heavy haze pollution events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Non-coding RNAs (ncRNAs) play important roles in regulating expression of protein-coding genes. Although gene expression databases have emerged in a timely manner, a comprehensive expression database for ncRNAs is still lacking. Herein, we constructed a rice ncRNA co-expression atlas (RiceNCexp), based on 491 RNA-seq and 274 small RNA (sRNA)-seq datasets. RiceNCexp hosts four types of ncRNAs, namely lncRNAs, PHAS genes, miRNAs, and phasiRNAs. RiceNCexp provides comprehensive expression information for rice ncRNAs in 22 tissues/organs, an efficient tau-based mining tool for tissue-specific ncRNAs, and the robust co-expression analysis among ncRNAs or between ncRNAs and protein-coding genes, based on 116 pairs of RNA-seq and sRNA-seq libraries from the same experiments. In summary, RiceNCexp is a user-friendly and comprehensive rice ncRNA co-expression atlas and can be freely accessed at https://cbi.njau.edu.cn/RiceNCexp/., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

There are plenty of mesoscale meteorological discontinuities in the atmosphere, acting as atmospheric internal boundaries (AIBs). In conjunction with the atmospheric boundary layer in the vertical direction, they form confined three-dimensional structures that significantly affect air pollution. However, the role of AIBs in regional pollution has not been systematically elucidated. Based on surface observations, this study investigates PM 2.5 pollution distributions under the forcing of various AIBs in the North China Plain. A total of 98 regional pollution episodes are identified during the autumn and winter of 2014-2020, and are further classified according to the impact of AIBs. In the pollution formation-maintenance stage, there are three categories. The frontal category (with a frequency of 41%), including the frontal trough type and frontal inverted trough type, displays the most polluted air masses along the mountains. The frontal AIB defines the lateral border of the pollution zone and forms a frontal inversion above, creating a closed and stable structure wherein the highest concentration of PM 2.5 accumulates. The wind shear category (29%) is decided by the dynamic convergence AIB, which causes lighter PM 2.5 pollution with diverse spatial patterns corresponding to west-southwest shear, southeast-east shear, and south-north shear. The topographic obstruction category (14%) presents as a narrow arc-shaped pollution belt at the foot of the windward mountains, resulting from the cold air damming AIB with dynamical obstruction and thermal stratification. Pollution diffuses in three ways: northwest, west, and northeast, respectively. The first one is the strongest and most frequent (42%), with both strong horizontal wind and vertical mixing. The second category is relatively rare (17%), characterized by foehn-induced active vertical ventilation. The last one is frequent (41%), but relatively weak, mainly relying on horizontal diffusion. Some evolution details of the AIB affecting PM 2.5 pollution are also illustrated by a typical case., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nitrogen-use efficiency (NUE) in rice is a complex quantitative trait involved in multiple biological processes and agronomic traits; however, the genetic basis and regulatory network of NUE remain largely unknown. We constructed a high-resolution microarray-based genetic map for 261 recombinant inbred lines derived from two indica parents. Using 2,345 bin markers, comprehensive analyses of quantitative trait loci (QTLs) of seven key agronomic traits under two different N levels were performed. A total of 11 non-redundant QTLs for effective panicle number (EPN), 7 for grain number per panicle, 13 for thousand-grain weight, 2 for seed-setting percentage, 15 for plant height, 12 for panicle length, and 6 for grain yield per plant were identified. The QTL regions were as small as 512 kb on average, and more than half spanned an interval smaller than 100 kb. Using this advantage, we identified possible candidate genes of two major EPN-related QTLs. One QTL detected under both N levels possibly encodes a DELLA protein SLR1, which is known to regulate NUE, although the natural variations of this protein have not been reported. The other QTL detected only under a high N level could encode the transcription factor OsbZIP59. We also predicted the possible candidate genes for another three of the NUE-related QTLs. Our results provide a reference for improving NUE-related QTL cloning and promote our understanding of NUE regulation in indica rice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Jiang, Yang, Han, Jin, Zhang, Chen, Chen and Teng.)

Aim: To define the clinical characteristics, hemodynamics, and adverse events for pediatric patients with pulmonary arterial hypertension (PAH) undergoing right heart catheterization (RHC). Methods: The large referral single center data of 591 diagnostic RHC procedures performed between 2005 and 2020 on pediatric PAH patients was retrospectively collected and analyzed. Results: A total of 591 RHC procedures performed on 469 patients with congenital heart disease (CHD)-PAH (median age 8.8 years, 7.9% New York Heart Association (NYHA) class > II, 1.5% with syncope) and 122 patients with idiopathic PAH (median age of 9.0 years, 27.0% NYHA class > II, 27.0% with syncope) were included. Of those, 373 (63.1%) procedures were performed under general anesthesia. Eighteen patients (18/591, 3.0%) suffered adverse events (mainly pulmonary hypertensive crisis, PHC, n = 17) during the RHC procedure, including 14 idiopathic pulmonary arterial hypertension (IPAH) patients and 4 CHD-PAH patients, and one IPAH patient died in hospital 63 hours after RHC. The risk of developing PHC was significantly increased in patients with IPAH (OR = 14.02, 95%CI: 4.49−43.85, p < 0.001), atrial blood gas pH < 7.35 (OR = 12.504, 95%CI: 3.545−44.102, p < 0.001) and RAP > 14 mmHg (OR = 10.636, 95%CI: 3.668−30.847, p < 0.001). Conclusions: RHC is generally a low-risk procedure in pediatric patients with PAH. However, PHC occur in approximately 3% of patients. Therefore, RHC should be performed in a large, experienced referral pediatric cardiology center, especially in pediatric patients with IPAH requiring general anesthesia., Competing Interests: The authors declare no conflict of interest.

Sodium (Na+) and potassium (K+) homeostasis is essential for plant survival in saline soils. A member of the High-Affinity K+ Transporter (HKT) family in rice (Oryza sativa), OsHKT1;1, is a vital regulator of Na+ exclusion from shoots and is bound by a MYB transcription factor (OsMYBc). Here, we generated transgenic rice lines in the oshkt1;1 mutant background for genetic complementation using genomic OsHKT1;1 containing a native (Com) or mutated (mCom) promoter that cannot be bound by OsMYBc. In contrast to wild-type (WT) or Com lines, the mCom lines were not able to recover the salt-sensitive phenotype of oshkt1;1. The OsMYBc-overexpressing plants were more tolerant to salt stress than WT plants. A yeast two-hybrid screen using the OsMYBc N-terminus as bait identified a rice MYBc stress-related RING finger protein (OsMSRFP). OsMSRFP is an active E3 ligase that ubiquitinated OsMYBc in vitro and mediated 26S proteasome-mediated degradation of OsMYBc under semi-in vitro and in vivo conditions. OsMSRFP attenuated OsMYBc-mediated OsHKT1;1 expression, and knockout of OsMSRFP led to rice salt tolerance. These findings uncover a regulatory mechanism of salt response that fine-tunes OsHKT1;1 transcription by ubiquitination of OsMYBc., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The turbulent transport of particles is normally assumed to be similar to the momentum (or heat) transport, both in observations and simulations. However, observations from the boundary layer reinforcement experiment conducted at the Pingyuan County Meteorological Bureau, Shandong Province, China, showed dissimilar turbulent transports for momentum, heat, and particles. Our results reveal the prevalence of ejection and sweep motions in the transport of momentum and heat but not in that of particles. For momentum transport, sweep motion is more efficient, and the contribution of ejection (sweeps) motion is higher during the day (night) for heat transport. Momentum transport may be affected by pollutants during heavy pollution episodes (HPEs), whereas heat transport is affected by pollutants at night during HPEs. The sink/source differences lead to differences in particle transport for different HPEs. Furthermore, the momentum motion does not transport heat and particles in the same manner, particularly during HPEs. Compared to heat and momentum transport, the transport of particles is not significantly affected by stability. The turbulent transport of momentum is often smaller than that of particles and heat. Therefore, certain dissimilarities exist in the turbulent transport of momentum, heat, and particles. Overall, these findings found by the observations shed some light on the turbulent transport of particles in mesoscale models, and the turbulent transport dissimilarities between momentum, heat, and particles have an important impact on correcting and obtaining an accurate particle flux., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Apolipoprotein E (APOE) plays a pivotal role in lipid including cholesterol metabolism. The APOE ε4 (APOE4) allele is a major genetic risk factor for Alzheimer's and cardiovascular diseases. Although APOE has recently been associated with increased susceptibility to infections of several viruses, whether and how APOE and its isoforms affect SARS-CoV-2 infection remains unclear. Here, we show that serum concentrations of APOE correlate inversely with levels of cytokine/chemokine in 73 COVID-19 patients. Utilizing multiple protein interaction assays, we demonstrate that APOE3 and APOE4 interact with the SARS-CoV-2 receptor ACE2; and APOE/ACE2 interactions require zinc metallopeptidase domain of ACE2, a key docking site for SARS-CoV-2 Spike protein. In addition, immuno-imaging assays using confocal, super-resolution, and transmission electron microscopies reveal that both APOE3 and APOE4 reduce ACE2/Spike-mediated viral entry into cells. Interestingly, while having a comparable binding affinity to ACE2, APOE4 inhibits viral entry to a lesser extent compared to APOE3, which is likely due to APOE4's more compact structure and smaller spatial obstacle to compete against Spike binding to ACE2. Furthermore, APOE ε4 carriers clinically correlate with increased SARS-CoV-2 infection and elevated serum inflammatory factors in 142 COVID-19 patients assessed. Our study suggests a regulatory mechanism underlying SARS-CoV-2 infection through APOE interactions with ACE2, which may explain in part increased COVID-19 infection and disease severity in APOE ε4 carriers., (© 2022. The Author(s).)

Heat perception enables acute avoidance responses to prevent tissue damage and maintain body thermal homeostasis. Unlike other modalities, how heat signals are processed in the spinal cord remains unclear. By single-cell gene profiling, we identified ErbB4, a transmembrane tyrosine kinase, as a novel marker of heat-sensitive spinal neurons in mice. Ablating spinal ErbB4+ neurons attenuates heat sensation. These neurons receive monosynaptic inputs from TRPV1+ nociceptors and form excitatory synapses onto target neurons. Activation of ErbB4+ neurons enhances the heat response, while inhibition reduces the heat response. We showed that heat sensation is regulated by NRG1, an activator of ErbB4, and it involves dynamic activity of the tyrosine kinase that promotes glutamatergic transmission. Evidence indicates that the NRG1-ErbB4 signaling is also engaged in hypersensitivity of pathological pain. Together, these results identify a spinal neuron connection consisting of ErbB4+ neurons for heat sensation and reveal a regulatory mechanism by the NRG1-ErbB4 signaling., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The cultivation of rice varieties with high seed vigour is vital for the direct seeding of rice, and the molecular basis of regulation of seed vigour remains elusive. Here, we cloned a new gene OsHIPL1, which encodes hedgehog-interacting protein-like 1 protein as a causal gene of the major QTL qSV3 for rice seed vigour. OsHIPL1 was mainly localized in the plasma membrane and nucleus. RNA sequencing (RNA-seq) revealed that the ABA-related genes were involved in the OsHIPL1 regulation of seed vigour in rice. The higher levels of endogenous ABA were measured in germinating seeds of OsHIPL1 mutants and NIL-qsv3 line compared to IR26 plants, with two up-regulated ABA biosynthesis genes (OsZEP and OsNCED4) and one down-regulated ABA catabolism gene OsABA8ox3. The expression of abscisic acid-insensitive 3 (OsABI3), OsABI4 and OsABI5 was significantly up-regulated in germinating seeds of OsHIPL1 mutants and NIL-qsv3 line compared to IR26 plants. These results indicate that the regulation of seed vigour of OsHIPL1 may be through modulating endogenous ABA levels and altering OsABIs expression during seed germination in rice. Meanwhile, we found that OsHIPL1 interacted with the aquaporin OsPIP1;1, then affected water uptake to promote rice seed germination. Based on analysis of single-nucleotide polymorphism data of rice accessions, we identified a Hap1 haplotype of OsHIPL1 that was positively correlated with seed germination. Our findings showed novel insights into the molecular mechanism of OsHIPL1 on seed vigour., (© 2022 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Terrestrial ecosystems in China receive the world's largest amount of reactive nitrogen (N) deposition. Recent controls on nitrogen oxides (NO x  = NO + NO 2 ) emissions in China to tackle air pollution are expected to decrease N deposition, yet the observed N deposition fluxes remain almost stagnant. Here we show that the effectiveness of NO x emission controls for reducing oxidized N (NO y  = NO x  + its oxidation products) deposition is unforeseen in Eastern China, with one-unit reduction in NO x emission leading to only 55‒76% reductions in NO y -N deposition, as opposed to the high effectiveness (around 100%) in both Southern China and the United States. Using an atmospheric chemical transport model, we demonstrate that this unexpected weakened response of N deposition is attributable to the enhanced atmospheric oxidizing capacity by NO x emissions reductions. The decline in N deposition could bear a penalty on terrestrial carbon sinks and should be taken into account when developing pathways for China's carbon neutrality., (© 2022. The Author(s).)