Dopamine Regulates Its Own Synthesis via MdORG2 to Improve Low-Nitrogen Tolerance in Apple Plants.

Nitrogen (N) is crucial for plant growth and development. Exogenous dopamine has been shown to improve the N-deficiency tolerance of apple. However, the potential regulatory mechanisms by which dopamine mitigates low-N stress remain unclear. Our data indicated that the dopamine levels in apple (Malus domestica) were elevated by the overexpression (OE) of MdTYDC, which encodes tyrosine decarboxylase, a key enzyme in dopamine biosynthesis. The photosynthetic capacity of the OE lines was enhanced, and the root system was more extensive under low-N stress compared with the wild-type (WT) plants. This enhancement contributed to a greater net nitrate influx at the root surface in the OE lines compared with the WT. Transcriptomic and carbohydrate analyses suggested that the OE of MdTYDC in apple enhanced N-deficiency tolerance by promoting the expression of carbohydrate-related genes, which increased the content of soluble sugars and sorbitol. Both exogenous dopamine and MdTYDC OE activated the expression of MdORG2 (a bHLH transcription factor), which, in turn, directly binds to the promoter of MdTYDC, activating its expression, increasing dopamine levels, and consequently conferring strong low-N tolerance in apple. Thus, this reveals the molecular pathways by which dopamine regulates low-N tolerance in apple through pathways involving MdTYDC and MdORG2.

Severe community­acquired pneumonia caused by Legionella gormanii in combination with influenza A subtype (H1N1) virus in an immunocompetent patient detected by metagenomic next­generation sequencing: A case report.

Legionella pneumonia is an atypical form of pneumonia caused by Legionella gormanii that can also lead to multiple organ diseases, including acute respiratory distress syndrome and multiple organ dysfunction syndrome. Legionella gormanii requires a long incubation period for culture in clinical practice using BCYE medium. The specificity of serum for serological detection is low, resulting in a relatively high rate of missed Legionella diagnoses. Contracting the H1N1 virus can lead to the misdiagnosis of Legionella gormanii. Metagenomic next-generation sequencing (mNGS) is a novel tool that can rapidly and accurately identify potential Legionella gormanii strains. A severe case of community-acquired pneumonia in a 79-year-old patient was reported. The patient was diagnosed with Legionella gormanii and influenza A subtype (H1N1) virus using mNGS at The First Affiliated Hospital, Zhejiang University School of Medicine. After anti-Legionella and antiviral therapy, the number of reads identifying Legionella gormanii in bronchoalveolar lavage fluid using mNGS decreased from 665 to 112 as the patient's condition gradually improved. A search of PubMed revealed few reports of Legionella gormanii in association with the influenza A subtype (H1N1) virus. Patients with severe pneumonia caused by Legionella and influenza A subtype H1N1 virus infections should be screened early for infections using methods such as mNGS. This approach enables early and precise treatment, simplifying the administration of antibiotics and enhancing patient outcomes.

The epigenetic mechanism of metabolic risk in bipolar disorder.

Bipolar disorder (BD) is a complex and severe mental illness that causes significant suffering to patients. In addition to the burden of depressive and manic symptoms, patients with BD are at an increased risk for metabolic syndrome (MetS). MetS includes factors associated with an increased risk of atherosclerotic cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), which may increase the mortality rate of patients with BD. Several studies have suggested a link between BD and MetS, which may be explained at an epigenetic level. We have focused on epigenetic mechanisms to review the causes of metabolic risk in BD.

Diagnosis with Metagenomic Next-Generation Sequencing (mNGS) technology and real-time PCR for SARS-CoV-2 Omicron detection using various nasopharyngeal swabs in SARS-CoV-2 Omicron.

BACKGROUND: The SARS-CoV-2 Omicron variant, with the main subtypes BA.5.2 and BF.7 in China, led to off-target effects on the S and N genes from December 1, 2022, to January 31, 2023. The kits used for studying and developing these agents were not adequately and independently evaluated. It is important to verify the performance of commercial Real-Time quantitative PCR (RT-qPCR) tests. OBJECTIVE: We conducted a clinical evaluation of two Real Time SARS-CoV-2 Omicron assays to verify their performance using various detection reagents and clinical specimens. METHODS: We performed clinical evaluations of two existing Chinese SARS-CoV-2 Omicron RT-qPCR kits 2019-nCoV nucleic acid diagnostic kits (Fosun Biotechnology, National instrument registration 20203400299, Shanghai, China) and COVID-19 nucleic acid detection kits (eDiagnosis Biomedicine, National instrument registration 20203400212, Wuhan, China) and using BSD (Bondson) (Guangzhou Bondson Biotechnology Co. Ltd, batch number 2022101), quality controls provided by the inspection center and a large number of clinically confirmed specimens. RESULTS: The concordance rates for the Fosun and eDiagnosis kits were 95% and 100%, respectively. The detection limit for the Fosun and eDiagnosis kits was verified to be 300 copies/mL and 500 copies/mL. The Fosun assay exhibited the largest coefficient of variation (CV) for ORF1ab and N gene at the detection limit concentration (4.80%, 3.49%), whereas eDiagnosis showed a smaller CV (0.93%, 1.10%). In the reference product from the Hangzhou Clinical Laboratory Center test, it was found that Fosun had the lowest sensitivity of 93.47% and a specificity of 100%, while eDiagnosis exhibited 100% for both sensitivity and specificity. The lowest single target gene detection rate of Fosun reagents was 68.7% for the ORF1ab gene and 87.5% for the N gene, while eDiagnosis detection rate was 100%. Among the clinical group S specimens, the missed detection rate of the Fosun reagent was 10.9%, which was higher than the 3.9% of eDiagnosis. However, there was no significant difference in the clinical diagnostic efficiency of the two reagents. CONCLUSIONS: The ORF1ab and N assays of SARS-CoV-2 Omicron on the eDiagnosis platform yielded higher values compared to those on the Fosun platform. Consequently, the eDiagnosis kit has also been used as standard detection reagents. Considering that the Fosun reagent has a relatively low detection limit and targets three single genes, it is more advantageous as a confirmatory reagent for the new museum.

[Clinical diagnosis and treatment analysis of spontaneous cerebrospinal fluid otorrhoea].

Objective:To investigate the clinical features, imaging findings, surgical methods， diagnostic and treatment experience of spontaneous cerebrospinal fluid otorrhoea. Methods:The clinical data of 11 patients with spontaneous cerebrospinal fluid otorrhoea treated surgically at our hospital from May 2018 to May 2023 were retrospectively analyzed. The medical data included medical history, imaging data, leak location, surgical repair method, treatment effect and postoperative follow-up. Results:Among the 11 surgical patients, 4 patients were initially diagnosed with secretory otitis media, 1 was initially diagnosed with purulent otitis media, and 5 patients had a history of meningitis or presented because meningitis as the initial diagnosis. There were 2 cases of cerebrospinal fluid leakage repaired through the ear canal pathway and 9 cases of cerebrospinal fluid leakage repaired through the mastoid pathway. During the operation, leaks were located in the stapes floor plate in 4 cases, sinus meningeal angle in 1 case, posterior cranial fossa combined with middle cranial fossa in 1 case, middle cranial fossa in 4 cases, and labyrinthine segment of the internal auditory canal and facial nerve canal in 1 case. Ten patient was successfully repaired, and another patient developed intracranial hypertension after surgery, with symptoms alleviated by a lateral ventriculoperitoneal shunt. Postoperative follow-up ranged from 6 months to 4 years, and there was no CSF otorrhoea and meningitis recurrence. Conclusion:The incidence of spontaneous cerebrospinal fluid otorrhea is low, the clinical symptoms are atypical, and the rate of delayed diagnosis or missed diagnosis and misdiagnosis is high. Surgery is currently the preferred treatment for spontaneous cerebrospinal fluid otorrhoea, and satisfactory results are usually achieved; During diagnosis and treatment, it is crucial to be vigilant for intracranial hypertension to prevent serious complications and irreversible damage.

The impact of impaired intrauterine growth on male fertility: A systematic review and meta-analysis.

BACKGROUND: Adverse intrauterine environment was believed to have deleterious effects on the gonadal function. However, the association between impaired intrauterine growth and fertility in adult males has not been established. OBJECTIVES: To compare the reproductive rates of males born small for gestational age (SGA), with low birth weight (LBW) or very low birth weight (VLBW) with control groups. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed to search PubMed, Web of Science, Cochrane Library, and Embase databases from inception to June 16, 2023. Cohort studies investigating the reproductive rates of males born SGA, with LBW or VLBW were included. A random or fixed effects model was used for different exposures. RESULTS: A total of 10 studies out of 3,801 records were included. Males born SGA showed a higher risk of infertility than the control group (odds ratio, OR = 0.91, 95% confidence interval, 95% CI 0.89-0.93, p = 0.000). The reproductive rates of individuals born with LBW or VLBW were lower than the control group (OR = 0.86, 95% CI 0.78-0.94, p = 0.001; OR = 0.57, 95% CI 0.40-0.81, p = 0.002, respectively). Participants were further divided into two age groups of 18-35 and 35-45 years. In both subgroups, the reproductive rates were lower in males born SGA, with LBW or VLBW compared with controls. Sensitivity analysis showed the robustness of the pooled estimates among LBW and VLBW. CONCLUSION: In summary, SGA, LBW, and VLBW were associated with a higher risk of male infertility in both early and middle adulthood. Achieving optimal intrauterine growth would be helpful to prevent male infertility.

Inadequate linear catch-up growth in children born small for gestational age: Influencing factors and underlying mechanisms.

A minority of children born small for gestational age (SGA) may experience catch-up growth failure and remain short in adulthood. However, the underlying causes and mechanisms of this phenomenon are not yet fully comprehended. We reviewed the present state of research concerning the growth hormone-insulin-like growth factor axis and growth plate in SGA children who fail to achieve catch-up growth. Additionally, we explored the factors influencing catch-up growth in SGA children and potential molecular mechanisms involved. Furthermore, we considered the potential benefits of supplementary nutrition, specific dietary patterns, probiotics and drug therapy in facilitating catch-up growth.

Stomatal evolution and plant adaptation to future climate.

Global climate change is affecting plant photosynthesis and transpiration processes, as well as increasing weather extremes impacting socio-political and environmental events and decisions for decades to come. One major research challenge in plant biology and ecology is the interaction of photosynthesis with the environment. Stomata control plant gas exchange and their evolution was a crucial innovation that facilitated the earliest land plants to colonize terrestrial environments. Stomata couple homoiohydry, together with cuticles, intercellular gas space, with the endohydric water-conducting system, enabling plants to adapt and diversify across the planet. Plants control stomatal movement in response to environmental change through regulating guard cell turgor mediated by membrane transporters and signaling transduction. However, the origin, evolution, and active control of stomata remain controversial topics. We first review stomatal evolution and diversity, providing fossil and phylogenetic evidence of their origins. We summarize functional evolution of guard cell membrane transporters in the context of climate changes and environmental stresses. Our analyses show that the core signaling elements of stomatal movement are more ancient than stomata, while genes involved in stomatal development co-evolved de novo with the earliest stomata. These results suggest that novel stomatal development-specific genes were acquired during plant evolution, whereas genes regulating stomatal movement, especially cell signaling pathways, were inherited ancestrally and co-opted by dynamic functional differentiation. These two processes reflect the different adaptation strategies during land plant evolution.

Macrophage polarization in adenomyosis: A review.

Adenomyosis (AM) is a common gynecological disorder characterized by the presence of endometrial glands and stroma within the uterine myometrium. It is associated with abnormal uterine bleeding (AUB), dysmenorrhea, and infertility. Although several mechanisms have been proposed to elucidate AM, the exact cause and development of the condition remain unclear. Recent studies have highlighted the significance of macrophage polarization in the microenvironment, which plays a crucial role in AM initiation and progression. However, a comprehensive review regarding the role and regulatory mechanism of macrophage polarization in AM is currently lacking. Therefore, this review aims to summarize the phenotype and function of macrophage polarization and the phenomenon of the polarization of adenomyosis-associated macrophages (AAMs). It also elaborates on the role and regulatory mechanism of AAM polarization in invasion/migration, fibrosis, angiogenesis, dysmenorrhea, and infertility. Furthermore, this review explores the underlying molecular mechanisms of AAM polarization and suggests future research directions. In conclusion, this review provides a new perspective on understanding the pathogenesis of AM and provides a theoretical foundation for developing targeted drugs through the regulation of AAM polarization.

T2T reference genome assembly and genome-wide association study reveal the genetic basis of Chinese bayberry fruit quality.

Chinese bayberry (Myrica rubra or Morella rubra; 2n = 16) produces fruit with a distinctive flavor, high nutritional, and economic value. However, previous versions of the bayberry genome lack sequence continuity. Moreover, to date, no large-scale germplasm resource association analysis has examined the allelic and genetic variations determining fruit quality traits. Therefore, in this study, we assembled a telomere-to-telomere (T2T) gap-free reference genome for the cultivar 'Zaojia' using PacBio HiFi long reads. The resulting 292.60 Mb T2T genome, revealed 8 centromeric regions, 15 telomeres, and 28 345 genes. This represents a substantial improvement in the genome continuity and integrity of Chinese bayberry. Subsequently, we re-sequenced 173 accessions, identifying 6 649 674 single nucleotide polymorphisms (SNPs). Further, the phenotypic analyses of 29 fruit quality-related traits enabled a genome-wide association study (GWAS), which identified 1937 SNPs and 1039 genes significantly associated with 28 traits. An SNP cluster pertinent to fruit color was identified on Chr6: 3407532 to 5 153 151 bp region, harboring two MYB genes (MrChr6G07650 and MrChr6G07660), exhibiting differential expression in extreme phenotype transcriptomes, linked to anthocyanin synthesis. An adjacent, closely linked gene, MrChr6G07670 (MLP-like protein), harbored an exonic missense variant and was shown to increase anthocyanin production in tobacco leaves tenfold. This SNP cluster, potentially a quantitative trait locus (QTL), collectively regulates bayberry fruit color. In conclusion, our study presented a complete reference genome, uncovered a suite of allelic variations related to fruit-quality traits, and identified functional genes that could be harnessed to enhance fruit quality and breeding efficiency of bayberries.

Increased circulating cell-free mitochondrial DNA in plasma of first-diagnosed drug-naïve bipolar disorder patients: A case-control and 4-week follow-up study.

BACKGROUND: The study of clinical biological indicators in bipolar disorder (BD) is important. In recent years, basic experiments have associated the pathophysiological mechanism of BD is related to mitochondrial dysfunction, but few clinical studies have confirmed this finding. OBJECT: The present study aimed to evaluate whether plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels, which can represent the degree of mitochondrial damage in vivo, are altered in patients with BD in early onset and during treatment compared with controls. METHOD: A total of 75 first-diagnosed drug-naive patients with BD and 60 HCs were recruited and followed up for 1 month. The clinical symptoms were assessed using HAMD, HAMA, and YMRS, and ccf-mtDNA levels were measured by qPCR before and after drug treatment in BD. RESULT: (1) The plasma ccf-mtDNA levels in first-diagnosed drug-naive patients with BD increased compared with those in HCs (p = 0.001). (2) Drug treatment for 1 month can decrease the expression of ccf-mtDNA in BD (p < 0.001). (3) No significant correlation was observed between the changes in ccf-mtDNA levels and the improvement of clinical symptoms in BD after drug treatment. CONCLUSION: The plasma ccf-mtDNA level was increased in BD, and decreased after pharmacological treatment. These outcomes suggested that plasma ccf-mtDNA level is likely to be sensitive to the drug response in BD, and mitochondrial pathway is a potential target for further therapy.

FGD1-related Aarskog-Scott syndrome: Identification of four novel variations and a literature review of clinical and molecular aspects.

Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype-phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism.   Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: • Aarskog-Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: • We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype-phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.

Cucurbitacin IIa promotes the immunogenic cell death­inducing effect of doxorubicin and modulates immune microenvironment in liver cancer.

The immunogenic cell death (ICD) has aroused great interest in cancer immunotherapy. Doxorubicin (DOX), which can induce ICD, is a widely used chemotherapeutic drug in liver cancer. However, DOX­induced ICD is not potent enough to initiate a satisfactory immune response. Cucurbitacin IIa (CUIIa), a tetracyclic triterpene, is a biologically active compound present in the Cucurbitaceae family. The present study assessed the effects of the combination of DOX and CUIIa on the viability, colony formation, apoptosis and cell cycle of HepG2 cells. In vivo anticancer effect was performed in mice bearing H22 tumor xenografts. The hallmark expression of ICD was tested using immunofluorescence and an ATP assay kit. The immune microenvironment was analyzed using flow cytometry. The combination of CUIIa and DOX displayed potent apoptosis inducing, cell cycle arresting and in vivo anticancer effects, along with attenuated cardiotoxicity in H22 mice. The combination of DOX and CUIIa also facilitated ICD as manifested by elevated high­mobility group box 1, calreticulin and ATP secretion. This combination provoked a stronger immune response in H22 mice, including dendritic cell activation, increment of cytotoxic T cells and T helper 1 cells. Moreover, the proportion of immunosuppressive cells including myeloid­derived suppressor cells, T regulatory cells and M2­polarized macrophages, decreased. These data suggested that CUIIa is a promising combination partner with DOX for liver cancer treatment, probably via triggering ICD and remolding the immune microenvironment.

Rapid detection of mexX in Pseudomonas aeruginosa based on CRISPR-Cas13a coupled with recombinase polymerase amplification.

The principal pathogen responsible for chronic urinary tract infections, immunocompromised hosts, and cystic fibrosis patients is Pseudomonas aeruginosa, which is difficult to eradicate. Due to the extensive use of antibiotics, multidrug-resistant P. aeruginosa has evolved, complicating clinical therapy. Therefore, a rapid and efficient approach for detecting P. aeruginosa strains and their resistance genes is necessary for early clinical diagnosis and appropriate treatment. This study combines recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats-association protein 13a (CRISPR-Cas13a) to establish a one-tube and two-step reaction systems for detecting the mexX gene in P. aeruginosa. The test times for one-tube and two-step RPA-Cas13a methods were 5 and 40 min (including a 30 min RPA amplification reaction), respectively. Both methods outperform Quantitative Real-time Polymerase Chain Reactions (qRT-PCR) and traditional PCR. The limit of detection (LoD) of P. aeruginosa genome in one-tube and two-step RPA-Cas13a is 10 aM and 1 aM, respectively. Meanwhile, the designed primers have a high specificity for P. aeruginosa mexX gene. These two methods were also verified with actual samples isolated from industrial settings and demonstrated great accuracy. Furthermore, the results of the two-step RPA-Cas13a assay could also be visualized using a commercial lateral flow dipstick with a LoD of 10 fM, which is a useful adjunt to the gold-standard qRT-PCR assay in field detection. Taken together, the procedure developed in this study using RPA and CRISPR-Cas13a provides a simple and fast way for detecting resistance genes.

A key mutation in magnesium chelatase I subunit leads to a chlorophyll-deficient mutant of tea (Camellia sinensis).

Tea (Camellia sinensis) is a highly important beverage crop renowned for its unique flavour and health benefits. Chlorotic mutants of tea, known worldwide for their umami taste and economic value, have gained global popularity. However, the genetic basis of this chlorosis trait remains unclear. In this study, we identified a major-effect quantitative trait locus (QTL), qChl-3, responsible for the chlorosis trait in tea leaves, linked to a non-synonymous polymorphism (G1199A) in the magnesium chelatase I subunit (CsCHLI). Homozygous CsCHLIA plants exhibited an albino phenotype due to defects in magnesium protoporphyrin IX and chlorophylls in the leaves. Biochemical assays revealed that CsCHLI mutations did not affect subcellular localization or interactions with CsCHLIG and CsCHLD. However, combining CsCHLIA with CsCHLIG significantly reduced ATPase activity. RNA-seq analysis tentatively indicated that CsCHLI inhibited photosynthesis and enhanced photoinhibition, which in turn promoted protein degradation and increased the amino acid levels in chlorotic leaves. RT-qPCR and enzyme activity assays confirmed the crucial role of asparagine synthetase and arginase in asparagine and arginine accumulation, with levels increasing over 90-fold in chlorotic leaves. Therefore, this study provides insights into the genetic mechanism underlying tea chlorosis and the relationship between chlorophyll biosynthesis and amino acid metabolism.

Molecular Genetic Analysis and Growth Hormone Treatment in a Three-Generation Chinese Family with Tricho-Rhino-Phalangeal Syndrome I.

INTRODUCTION: Tricho-rhino-phalangeal syndrome (TRPS) is a rare genetic disorder characterized by craniofacial and skeletal abnormalities, which is caused by variants in the TRPS1 gene. METHODS: Clinical information and follow-up data were collected. Whole-exome sequencing (WES) was performed for variants and validated by Sanger sequencing. Bioinformatic analysis was performed to predict the pathogenicity of the identified variant. Moreover, wild-type and mutated TRPS1 vectors were constructed and transfected into human embryonic kidney (HEK) 293T cells. Immunofluorescence experiments were performed to assess the localization and expression of the mutated protein. Western blot analysis and RT-qPCR were used to detect the expression of downstream genes. RESULTS: The affected family members had typical craniofacial phenotype including sparse lateral eyebrows, pear-shaped nasal tip, and large prominent ears, plus skeletal abnormalities including short stature and brachydactyly. WES and Sanger sequencing identified the TRPS1 c.880_882delAAG variant in affected family members. In vitro functional studies showed that the TRPS1 variant did not affect the cellular localization and the expression of TRPS1, but the transcriptional repression effect of the TRPS1 on the RUNX2 and STAT3 was disturbed. The proband and his brother have been treated with growth hormone (GH) for 2 years until now, and we have observed the improvement of the linear growth in both. CONCLUSIONS: The variant of c.880_882delAAG in TRPS1 was responsible for the pathogenesis of the Chinese family with TRPS I. The treatment of GH could be beneficial for the height outcome in TRPS I patients, and earlier initiation and longer duration of the therapy in prepubertal or early pubertal stage could be associated with better height outcomes.

Osteoporosis and low bone mass among schizophrenia and bipolar disorder: A cross-sectional study with newly diagnosed, drug-naïve subjects.

BACKGROUND: A growing body of data shows that schizophrenia (SCZ) and bipolar disorder (BD) have substantial metabolic risks; however, few studies have focused on bone metabolism. This study aimed to assess the prevalence and associated influencing factors of low bone mass and osteoporosis in SCZ and BD before pharmacological effects occur. METHODS: 108 healthy controls (HCs) and drug-naïve individuals with SCZ (n = 56) and BD (n = 130) had their lumbar spine (L1-L4) and left femur (Neck/Trochanter/Ward's triangle) bone mineral density (BMD) determined using dual-energy X-ray absorptiometry. Besides, we measured bone turnover markers (BTMs) levels, including procollagen I N-terminal propeptide, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen in different groups. RESULTS: Individuals with SCZ and BD had significantly lower BMD and significantly higher prevalence of low bone mass and osteoporosis compared with HCs. In the main observation regions of the total lumbar (F = 18.368, p < 0.001) and left femur (F = 14.790, p < 0.001), BMD was lower in individuals with SCZ and BD than HCs, with SCZ showing lower BMD than BD. The osteocalcin (H = 11.421, p = 0.003) levels were significantly higher in SCZ and BD than HCs. Binary regression analysis showed that SCZ or BD was an independent risk factor for low bone mass and osteoporosis. In addition, sex, age, and BTMs also influenced the occurrence of low bone mass and osteoporosis. LIMITATIONS: Cross-sectional study. CONCLUSION: The results findings of the study might contribute to our understanding of the increased risk of bone metabolism in SCZ and BD. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR1900021379.

How to achieve carbon neutrality and low-carbon economic development-evidence from provincial data in China.

"Carbon Peaking and Carbon Neutrality" is a major strategy for China to cope with climate change at present. We define the carbon neutrality capability (CNC) to reflect the current situation of regional carbon neutrality, and propose a new coupling model to explore the coupling relationship between regional economic development and carbon neutrality capability (CNC). Finally, the influence mechanism of the energy consumption structure on CNC was further discussed by using STRIPAT model. The results show that: during we study period, the national average carbon sink was about 77.89 Mt, and the carbon sinks in Inner Mongolia, Heilongjiang, Sichuan and Yunnan were as high as 164 Mt, mainly concentrated in the western region. The national average carbon source is 222.12 Mt, which is about three times that of carbon sink. The carbon source in Shandong, Hebei and Jiangsu are as high as 400 Mt or more, mainly concentrated in the eastern region. In addition, the growth rate of carbon source is much faster than that of carbon sink, especially the carbon emission caused by energy consumption, which leads to a general decline in CNC, and the development of CNC in various provinces is not optimistic. CNC and economic development level of most provinces are in a state of recession decoupling, and the coupling state of the provinces studied in certain years is significantly different. The spatial distribution of CNC and GDP has shown a northeast-southwest pattern. In addition, the influence of coal consumption structure on CNC is significantly negative, so we should optimize the energy consumption structure and increase the proportion of clean energy consumption. This study can make clear the current carbon neutrality capability of provinces in China, facilitate the formulation and adjustment of emission reduction strategies of provinces and cities, and help China to achieve carbon neutrality as soon as possible.

Development and validation of functional kompetitive allele-specific PCR markers for herbicide resistance in Brassica napus.

Effective weed control in the field is essential for maintaining favorable growing conditions and rapeseed yields. Sulfonylurea herbicides are one kind of most widely used herbicides worldwide, which control weeds by inhibiting acetolactate synthase (ALS). Molecular markers have been designed from polymorphic sites within the sequences of ALS genes, aiding marker-assisted selection in breeding herbicide-resistant rapeseed cultivars. However, most of them are not breeder friendly and have relatively limited application due to higher costs and lower throughput in the breeding projects. The aims of this study were to develop high throughput kompetitive allele-specific PCR (KASP) assays for herbicide resistance. We first cloned and sequenced BnALS1 and BnALS3 genes from susceptible cultivars and resistant 5N (als1als1/als3als3 double mutant). Sequence alignments of BnALS1 and BnALS3 genes for cultivars and 5N showed single nucleotide polymorphisms (SNPs) at positions 1676 and 1667 respectively. These two SNPs for BnALS1 and BnALS3 resulted in amino acid substitutions and were used to develop a KASP assay. These functional markers were validated in three distinct BC1F2 populations. The KASP assay developed in this study will be valuable for the high-throughput selection of elite materials with high herbicide resistance in rapeseed breeding programs.

Single-cell immune profiling reveals broad anti-inflammation response in bipolar disorder patients with quetiapine and valproate treatment.

Bipolar disorder (BD) is a common mental disorder characterized by manic and depressive episodes. Mood disorders have been associated with immune dysfunction. The combination of quetiapine and valproate has shown positive effects in treating BD, but the impact on immune dynamics remains less understood. Using single-cell RNA sequencing, we observed that B cells exhibited downregulation of inflammation-related genes, while pro-inflammatory mast and eosinophil cells decreased following treatment. Ribosomal peptide production genes were found to be reduced in both B and T cells after treatment. Additionally, our findings suggest that the combined therapy effectively alleviates inflammation by reducing myloid-mediated immune signaling pathways. This study provides valuable insights into the immune atlas and uncovers a potential mechanism for immune disorder alleviation in patients with BD treated with quetiapine and valproate.