Association between gut microbiota and spinal stenosis: a two-sample mendelian randomization study.

Introduction: Considerable evidence has unveiled a potential correlation between gut microbiota and spinal degenerative diseases. However, only limited studies have reported the direct association between gut microbiota and spinal stenosis. Hence, in this study, we aimed to clarify this relationship using a two-sample mendelian randomization (MR) approach. Materials and Methods: Data for two-sample MR studies was collected and summarized from genome-wide association studies (GWAS) of gut microbiota (MiBioGen, n = 13, 266) and spinal stenosis (FinnGen Biobank, 9, 169 cases and 164, 682 controls). The inverse variance-weighted meta-analysis (IVW), complemented with weighted median, MR-Egger, weighted mode, and simple mode, was used to elucidate the causality between gut microbiota and spinal stenosis. In addition, we employed mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and the MR-Egger intercept test to assess horizontal multiplicity. Cochran's Q test to evaluate heterogeneity, and "leave-one-out" sensitivity analysis to determine the reliability of causality. Finally, an inverse MR analysis was performed to assess the reverse causality. Results: The IVW results indicated that two gut microbial taxa, the genus Eubacterium fissicatena group and the genus Oxalobacter, have a potential causal relationship with spinal stenosis. Moreover, eight potential associations between genetic liability of the gut microbiota and spinal stenosis were implied. No significant heterogeneity of instrumental variables or horizontal pleiotropy were detected. In addition, "leave-one-out" sensitivity analysis confirmed the reliability of causality. Finally, the reverse MR analysis revealed that no proof to substantiate the discernible causative relationship between spinal stenosis and gut microbiota. Conclusion: This analysis demonstrated a possible causal relationship between certain particular gut microbiota and the occurrence of spinal stenosis. Further studies focused on the mechanism of gut microbiota-mediated spinal stenosis can lay the groundwork for targeted prevention, monitoring, and treatment of spinal stenosis.

Fibroblast Activation Protein Inhibitor Tracers and Their Preclinical, Translational, and Clinical Status in China.

Quinoline-based fibroblast activation protein (FAP) inhibitors (FAPIs) have recently emerged as a focal point in global nuclear medicine, underscored by their promising applications in cancer theranostics and the diagnosis of various nononcological conditions. This review offers an in-depth summary of the existing literature on the evolution and use of FAPI tracers in China, tracing their journey from preclinical to clinical research. Moreover, this review also assesses the diagnostic accuracy of FAPI PET for the most common cancers in China, analyzes its impact on oncologic management paradigms, and investigates the potential of FAP-targeted radionuclide therapy in patients with advanced or metastatic cancer. This review also summarizes studies using FAPI PET for nononcologic disorders in China. Thus, this qualitative overview presents a snapshot of China's engagement with FAPI tracers, aiming to guide future research endeavors.

Using a golf specific functional movement screen to predict golf performance in collegiate golfers.

Background: This study aims to examine the relationship between functional movements and golf performance using the Golf Specific Functional Movement Screen (GSFMS). Methods: This cross-sectional study included a total of 56 collegiate golfers (aged 20.89 ± 0.99 years, height of 174.55 ± 7.76 cm, and weight 68.48 ± 9.30 kg) who met the criteria, and were recruited from Hainan Normal University in June 2022. The participants' golf motor skills (1-yard putt, 10-yard putt, 25-yard chip, 130/100-yard set shot, driver, and 9-hole stroke play) were tested and the GSFMS (e.g., pelvic tilt, pelvic rotation, and torso rotation) was used. Results: There were significant weak or moderate correlations between the variables. Furthermore, a multiple linear regression analysis found that pelvic rotation and lower-body rotation abilities can significantly predict golf skill levels, which collectively explain 31.2% of the variance in golf skill levels among collegiate golfers (Adjusted R2 = 0.312, F = 2.663, p < 0.05). Standardised ß values indicate that pelvic rotation (ß = 0.398) has a more substantial impact on golf skill levels than lower-body rotation (ß = 0.315). Conclusions: This study found the weak to moderate correlations between the GSFMS and golf performance, and pelvic rotation and lower-body rotation abilities, thus predicting golf skills. Our findings provide novel insights into the relationship between functional abilities and comprehensive skill performance within the context of the Gray Cook's Movement Pyramid model, and provide theoretical support and practical reference for collegiate golf motor-skill learning and sports injury prevention.

[Determination of 12 prohibited veterinary drug residues in pig urine by ultra high performance liquid chromatography-tandem mass spectrometry].

A method was established for the simultaneous detection of 12 prohibited veterinary drugs, including ß2-receptor agonists, nitrofuran metabolites, nitroimidazoles, chlorpromazine, and chloramphenicol, in pig urine. The sample was pretreated by enzymolysis, acid hydrolysis/derivatization, and liquid-liquid extraction combined with solid-phase extraction. Detection was performed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Ammonium acetate solution (0.2 mol/L, 4.5 mL) and ß-glucuronidase/aryl sulfatase (40 µL) were added to the sample, which was subsequently enzymolized at 37 ℃ for 2 h. Then, 1.5 mL of 1.0 mol/L hydrochloric acid solution and 100 µL of 0.1 mol/L o-nitrobenzaldehyde solution were added to the sample. The mixture was incubated at 37 ℃ for 16 h, and the analytes were extracted with 8 mL of ethyl acetate by liquid-liquid extraction. The lower aqueous phase obtained after extraction was extracted and purified using a mixed cation-exchange solid-phase extraction column. The extracts were combined, the extraction solution was blow-dried with nitrogen, and the residue was redissolved for determination. The samples were analyzed under multiple-reaction monitoring mode with both positive and negative electrospray ionization, and quantified using an isotope internal standard method. The correlation coefficients (r) of the 12 compounds were >0.99. The limits of detection (LODs) and quantification (LOQs) of chloramphenicol were 0.05 and 0.1 µg/L, respectively, and the LODs and LOQs of the other compounds were 0.25 and 0.5 µg/L, respectively. The mean recoveries and RSDs at 1, 2, and 10 times the LOQ were 83.6%-115.3% and 2.20%-12.34%, respectively. The proposed method has the advantages of high sensitivity, good stability, and accurate quantification; thus, it is suitable for the simultaneous determination of the 12 prohibited veterinary drug residues in pig urine.

Fractured vertebra antedisplacement reconstruction technique: a feasible treatment choice for posttraumatic thoracolumbar kyphosis.

OBJECTIVE: The goal of this study was to evaluate the feasibility of the fractured vertebra antedisplacement reconstruction technique for the treatment of posttraumatic thoracolumbar kyphosis (PTK). METHODS: A total of 22 patients with PTK who were treated with the fractured vertebra antedisplacement reconstruction technique were retrospectively analyzed. The radiological evaluation included global kyphosis, thoracolumbar angle, and sagittal vertical axis. The clinical evaluation included visual analog scale pain score, Oswestry Disability Index score, SF-12 Health Survey score, and American Spinal Injury Association grade. The complications were recorded. RESULTS: The mean global kyphosis was 55.0° ± 12.6° preoperatively, 8.5° ± 5.0° postoperatively, and 10.3° ± 4.8° at the latest follow-up (p < 0.001). The average total kyphosis correction achieved was 44.7° ± 14.2°, with a range of 23.4°-79.4°, indicating a mean final correction of 80.1%. The mean thoracolumbar angle was 46.2° ± 13.2° preoperatively, 6.6° ± 4.5° postoperatively, and 7.6° ± 4.2° at the latest follow-up (p < 0.001). The mean sagittal vertical axis was improved significantly, from 51.1 ± 24.2 mm preoperatively to 28.5 ± 17.4 mm at the latest follow-up (p = 0.001). One patient (4.5%) experienced single intervertebral fusion nonunion, and 1 patient (4.5%) experienced distal screw loosening. No patients experienced any neurological deterioration. The visual analog scale pain score, Oswestry Disability Index score, SF-12 Health Survey score, and American Spinal Injury Association grade achieved significant improvement at the latest follow-up. CONCLUSIONS: Fractured vertebra antedisplacement reconstruction technique can effectively correct kyphosis, reconstruct spinal stability, and improve the patient's symptoms and neurological function. This technique is safer, minimally traumatic, and less technically demanding to avoid osteotomy-related complications. It is a feasible treatment choice for PTK.

Polystyrene microplastics disturb maternal glucose homeostasis and induce adverse pregnancy outcomes.

Pregnant women are a special group that is sensitive to adverse external stimuli, causing metabolic abnormalities and adverse pregnancy outcomes. Microplastics (MPs), an environmental pollutant widely used in various fields, can induce a variety of toxic responses in mammals. Recent studies verified an association between MPs and metabolic disorders. Our research built a gestational mouse model in which polystyrene microplastics (PS-MPs) of 1 µm size were consumed at concentrations of 0.1, 1, and 10 mg/L during pregnancy. Results indicated that PS-MPs induced placental malfunction and fetal growth retardation. Significant glucose disorders, decreased liver function, hepatic inflammation, and oxidative stress were also observed after PS-MPs exposure. The hepatic SIRT1/IRS1/PI3K pathway was inhibited in the 10 mg/L PS-MPs exposure group. Our study found that PS-MPs activated inflammatory response and oxidative stress by increasing hepatic lipopolysaccharide (LPS) that inhibited the hepatic SIRT1/IRS1/PI3K pathway, ultimately leading to insulin resistance, glucose metabolism disorders, and adverse pregnancy outcomes. This study provides a basis for preventing environment-related gestational diabetes and concomitant adverse pregnancy outcomes.

Isolation of anthraquinone derivatives from Rubia cordifolia (Rubiaceae) and their bioactivities against plant pathogenic microorganisms.

BACKGROUND: The discovery of antimicrobial ingredients from natural products could be an effective way to create novel fungicides. Rubia cordifolia L., a traditional Chinese herb, may have antimicrobial effects on plant pathogens according to our previous screening study. RESULTS: Rubia cordifolia L. extracts had moderate inhibitory effects on apple Valsa canker (Valsa mali) and tomato grey mould (Botrytis cinerea) at a concentration of 10 mg mL-1. With the use of bioguided isolation methods, eight compounds (1-8) were obtained, including the new compound 2,2,6-trimethyl-6-(4-methylphenyl)-tetrahydropyrano- 3-ol (7), and seven quinone derivatives. Two compounds, mollugin (1) and 1,3,6-trihydroxy-2-methylanthraquinone (6), were found to exhibit outstanding antifungal activities against V. mali and Phytophthora capsici Leon. The half maximal effective concentration (EC50) of compound 1 and compound 6 against V. mali were 79.08 and 81.78 µg mL-1, respectively, and the EC50 of compound 6 against P. capsici was 4.86 µg mL-1. Compound 1 also showed excellent activity against tobacco mosaic virus (TMV). The inactive, inductive, protective and curative activities against TMV were 84.29%, 83.38%, 86.81%, and 60.02%, respectively, at a concentration of 500 µg mL-1, which were all close to or greater than that of the positive control (100 µg mL-1 chitosan oligosaccharide, COS). CONCLUSION: Mollugin and 1,3,6-trihydroxy-2-methylanthraquinone are potentially valuable active compounds that lay a foundation for research on botanical fungicide products derived from R. cordifolia L. and provide lead structures for quinone derivative synthesis and structural modification. © 2024 Society of Chemical Industry.

A novel NIR-II FL/ PA imaging-guided synergistic photothermal-immune therapy: Biomineralizing nanosystems integrated with anti-tumor and bone repair.

Advanced stages of breast cancer are frequently complicated by bone metastases, which cause significant cancer-related bone destruction and mortality. However, the early precise theranostics of bone metastasis remains a formidable challenge in clinical practice. Herein,a novel all-in-one nanotheranostic system (ABI NYs) combining NIR-II FL/PA dual-modal imaging with photothermal-immunity therapeutic functionalities in one component was designed to precisely localize bone metastasis microscopic lesions and achieve complete tumor ablation at an early stage. The surface modification of the nanosystem with ibandronate (IBN) facilitates both passive and active targeting, significantly improving the detection rate of bone metastasis and suppressing the bone resorption. Superior photothermal performance produces sufficient heat to kill tumor cells while stimulating the upregulation of heat shock proteins 70 (HSP70), which triggers the immunogenic cell death (ICD) effect and the anti-tumor immune response. These all-in-one nanosystems precisely demonstrated early lesion localization in bone metastases and total tumor ablation with a single integration via "one-component, multi-functions" technique. To sum up, ABI NYs, as novel biomineralizing nanosystems integrated with anti-tumor and bone repair, present a synergistic therapy strategy, providing insight into the theranostics of bone metastases and clinical research.

First Report of Powdery Mildew Caused by Podosphaera xanthii on Youngia japonica subsp. elstonii in Hainan Province, China.

Youngia japonica (L.) DC. is a polymorphic annual herb of the Asteraceae family. Although this plant originated in Asia, it is now world-widely distributed. In China, Y. japonica is used for edible or folk medicine to treat viral infections and various kinds of inflammation (Yu et al. 2021). As a traditional Chinese medicinal herb, Y. japonica used for the treatment of inflammatory diseases, such as angina, leucorrhea, mastitis, conjunctivitis, and rheumatoid arthritis (Chen et al. 2006). During the spring of 2023, powdery mildew symptoms were observed on 60% of Y. japonica subsp. elstonii plants in a greenhouse on the Hainan Medical University campus (19° 58' 53″ N; 110° 19' 47″ E) in Haikou, Hainan Province, China. Powdery mildew colonies covered the leaf surfaces and stems of affected plants, causing discoloration and defoliation. Mycelia were superficial and hyphal appressoria were nipple-shaped. Conidiophores (n =30) were unbranched, cylindrical, 99 to 166 × 11 to 16 µm, and produced three to five immature conidia in chains with a crenate outline. Foot cells (n =30) were cylindrical, straight or sometimes curved at the base, and 35 to 61 µm long. Conidia (n =100) were ellipsoid-ovoid to doliiform, 21 to 40 ×13 to 21 µm (length/width ratio = 1.4 to 2.3), with well-developed fibrosin bodies, and produced germ tubes from the lateral position. Based on these morphological characteristics, the pathogen was provisionally identified as Podosphaera xanthii (Braun and Cook 2012). The teleomorph was not observed. A specimen was deposited in the Hainan Medical University Plant Pathology Herbarium as HMYJ-23. To confirm the genus identification and ascertain a putative species, genomic DNA was extracted from mycelium, conidiophores, and conidia using a fungal DNA kit (Omega Bio-Tek, USA). The rDNA internal transcribed spacer (ITS) region was amplified with primers ITS1/ITS4 (White et al. 1990) and sequenced directly. The resulting 575-bp sequence was deposited in GenBank (accession no. OR229712). A BLASTn search in GenBank of this sequence showed 99% similarity with the ITS sequences of P. xanthii isolates from China (MT260063, OP765400, MW422608, and MT739423), Thailand (LC270778, LC270779, and LC270780), and Argentina (AB525914). Additionally, the 613-bp 28S rDNA region was amplified using the primer pairs NL1 and NL4 (O'Donnell 1993; accession no. OR240257). This region shared 100% similarity with P. xanthii isolates (MK357436, LC371333, LC270780, OP765401, and AB936277) as well. To confirm pathogenicity, five healthy potted plants of Y. japonica subsp. elstonii were inoculated by gently pressing a powdery mildew-infected leaf onto the young leaves. Five non-inoculated plants served as controls. All plants were maintained in a greenhouse at 24 to 30°C, 70% relative humidity, with a 16-h photoperiod. After 7 days, inoculated leaves showed powdery mildew symptoms whereas no symptoms were observed on control plants. The fungal colonies observed on inoculated plants were morphologically identical to those found on the originally infected leaves collected from Hainan Province. Based on the morphological characteristics and molecular identification, the fungus was identified as P. xanthii. To our knowledge, this is the first record of P. xanthii infecting Y. japonica subsp. elstonii in Hainan province, China. We are concerned that the pathogen could become a threat to the widespread planting of Y. japonica subsp. elstonii in the future.

MSC-derived mitochondria promote axonal regeneration via Atf3 gene up-regulation by ROS induced DNA double strand breaks at transcription initiation region.

BACKGROUND: The repair of peripheral nerve injury poses a clinical challenge, necessitating further investigation into novel therapeutic approaches. In recent years, bone marrow mesenchymal stromal cell (MSC)-derived mitochondrial transfer has emerged as a promising therapy for cellular injury, with reported applications in central nerve injury. However, its potential therapeutic effect on peripheral nerve injury remains unclear. METHODS: We established a mouse sciatic nerve crush injury model. Mitochondria extracted from MSCs were intraneurally injected into the injured sciatic nerves. Axonal regeneration was observed through whole-mount nerve imaging. The dorsal root ganglions (DRGs) corresponding to the injured nerve were harvested to test the gene expression, reactive oxygen species (ROS) levels, as well as the degree and location of DNA double strand breaks (DSBs). RESULTS: The in vivo experiments showed that the mitochondrial injection therapy effectively promoted axon regeneration in injured sciatic nerves. Four days after injection of fluorescently labeled mitochondria into the injured nerves, fluorescently labeled mitochondria were detected in the corresponding DRGs. RNA-seq and qPCR results showed that the mitochondrial injection therapy enhanced the expression of Atf3 and other regeneration-associated genes in DRG neurons. Knocking down of Atf3 in DRGs by siRNA could diminish the therapeutic effect of mitochondrial injection. Subsequent experiments showed that mitochondrial injection therapy could increase the levels of ROS and DSBs in injury-associated DRG neurons, with this increase being correlated with Atf3 expression. ChIP and Co-IP experiments revealed an elevation of DSB levels within the transcription initiation region of the Atf3 gene following mitochondrial injection therapy, while also demonstrating a spatial proximity between mitochondria-induced DSBs and CTCF binding sites. CONCLUSION: These findings suggest that MSC-derived mitochondria injected into the injured nerves can be retrogradely transferred to DRG neuron somas via axoplasmic transport, and increase the DSBs at the transcription initiation regions of the Atf3 gene through ROS accumulation, which rapidly release the CTCF-mediated topological constraints on chromatin interactions. This process may enhance spatial interactions between the Atf3 promoter and enhancer, ultimately promoting Atf3 expression. The up-regulation of Atf3 induced by mitochondria further promotes the expression of downstream regeneration-associated genes and facilitates axon regeneration.

CircBCL2L13 attenuates cardiomyocyte oxidative stress and apoptosis in cardiac ischemia‒reperfusion injury via miR-1246/PEG3 signaling.

Ischemia‒reperfusion (I/R) is a common complication in the clinical treatment of acute myocardial infarction (MI), in which cardiomyocytes play a pivotal role in the recovery of cardiac function after reperfusion injury. The expression of numerous circular ribonucleic acids (circRNAs) is disrupted in I/R-induced cardiac damage, but the potential role of circRNAs in I/R damage has not been fully elucidated. The purpose of the present study was to clarify the biological action and molecular mechanism of circRNA 002166 (also termed circCL2L13) in postmyocardial I/R. Oxygen-glucose deprivation/reoxygenation (OGD/R) in an in vivo model was performed to simulate I/R damage. real-time polymerase chain reaction analysis was also conducted to evaluate the relationships of the SOD1, SOD2, NRF2, HO1 and GPX4 indicators with oxidative stress injury. TUNEL immunofluorescence was used to evaluate the degree of cardiomyocyte apoptosis in the different treatment groups. The circBCL2L13 level was markedly upregulated in myocardial tissues from a mouse I/R model. Overexpression of circBCL2L13 markedly attenuated the expression of oxidative stress-related genes and apoptosis in OGD/R-induced cardiomyocytes. A mechanistic study revealed that circBCL2L13 functions as a ceRNA for miR-1246 and modulates paternally expressed gene 3 (PEG3). Eventually, circBCL2L13 was proven to regulate PEG3 by targeting miR-1246, thereby protecting against OGD/R-induced cardiomyocyte oxidative damage and apoptosis. In conclusion, our study confirmed that the circBCL2L13/miR-1246/PEG3 axis suppressed the progression of OGD/R injury in cardiomyocytes, which might lead to new therapeutic strategies for cardiac I/R injury.

Interleukin-6 signaling pathway in Mendelian randomization: A 10-year bibliometric analysis.

Interleukin 6 (IL-6), a pleiotropic cytokine, is crucial in a variety of inflammatory and immunological disorders. In recent years, mendelian randomization, which is a widely used and successful method of analyzing causality, has recently been investigated for the relationship between the IL-6 pathway and related diseases. However, no studies have been conducted to review the research hotspots and trends in the field of IL-6 signaling pathway in Mendelian randomization. In this study, the Web of Science Core Collection (WoSCC) served as our literature source database to gather articles about the IL-6 signaling pathway in Mendelian randomization from 2013 to 2023. VOSviewer (version 1.6.18), Microsoft Excel 2021, and Scimago Graphica were employed for bibliometric and visualization analysis. A total of 164 documents that were written by 981 authors coming from 407 institutions across 41 countries and published in 107 journals were located from January 2013 to August 2023. With 64 and 25, respectively, England and the University of Bristol had the highest number of publications. Frontiers in Immunology is the most prolific journal, and Golam M Khandaker has published the highest number of significant articles. The most co-cited article was an article entitled the interleukin-6 receptor as a target for prevention of coronary-heart-disease: a Mendelian randomization analysis, written by Daniel I Swerdlow. The most popular keywords were "mendelian randomization," "interleukin-6," "il-6," "c-reactive protein," "association," "coronary-heart-disease," "inflammation," "instruments," "risk," "rheumatoid arthritis," "depression." The full extent of the existing literature over the last 10 years is systematically revealed in this study, which can provide readers with a valuable reference for fully comprehending the research hotspots and trends in the field of IL-6 signaling pathway in Mendelian randomization.

Voacangine mitigates oxidative stress and neuroinflammation in middle cerebral artery occlusion-induced cerebral ischemia/reperfusion injury by averting the NF-κBp65/MAPK signaling pathways in rats.

Ischemic stroke is a leading cause of human mortality. Cerebral ischemia-reperfusion injury (CI/RI) is a primary cause of stroke. Ischemia-reperfusion (I/R) resulting in oxidative stress and inflammatory events may lead to severe neuronal impairments. Thus, anti-oxidative and anti-inflammatory mediators that can alleviate post-I/R neuronal injuries are required for the treatment of CI/RI. An alkaloid, voacangine (VCG) is a recognized antioxidant, anti-inflammatory, and anticancer agent. Hence, the current study intended to explore the neuroprotective potential and the principal mechanisms of VCG in CI/RI. The experimental rats were divided into four sets: control, I/R-induced, I/R + VCG (2.5 mg/kg), I/R + VCG (5 mg/kg). CI/RI was induced by implanting a thread into the middle cerebral artery occlusion (MCAO) model. Brain damages were assessed on the basis of brain edema, brain infarct volume, neurological deficit score, histopathology, oxidative stress, and neuroinflammation. Results revealed that VCG inhibited the triggering of NLRP3 inflammasome, pro-inflammatory cytokines, lipid peroxidation, but enhanced the antioxidant status in MCAO rats. Furthermore, VCG treatment averted brain damage by I/R, neuroinflammation, and oxidative stress by suppressing NF-κBp65/MAPK pathways. The results of the study provide pertinent insights pertaining to the role of VCG as a potential neuroprotective agent against ischemic stroke.

Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy.

Background: Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti-inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro. Methods: In vitro, western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin-1 beta (IL-1ß)-induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture-induced IVDD rat models. Results: In vitro, API played a crucial role in anti-inflammation and autophagy enhancement in IL-1ß-induced NPCs. API improved inflammation by inhibiting the nuclear factor-kappaB and mitogen-activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3-kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture-induced IVDD model. Conclusions: API inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.

Catalytic Asymmetric Cyclizative Rearrangement of Anilines and Vicinal Diketones to Access 2,2-Disubstituted Indolin-3-ones.

The efficient synthesis of chiral 2,2-disubstituted indolin-3-ones is of great importance due to its significant synthetic and biological applications. However, catalytic enantioselective methods for de novo synthesis of such heterocycles remain scarce. Herein, a novel cyclizative rearrangement of readily available anilines and vicinal diketones for the one-step construction of enantioenriched 2,2-disubstituted indolin-3-ones is presented. The reaction proceeds through a self-sorted [3+2] heteroannulation/regioselective dehydration/1,2-ester shift process. Only chiral phosphoric acid is employed to promote the entire sequence and simplify the manipulation of this protocol. Various common aniline derivatives are successfully applied to asymmetric synthesis as 1,3-binuclephiles for the first time. Remarkably, the observed stereoselectivity is proposed to originate from an amine-directed regio- and enantioselective ortho-Csp2-H addition of the anilines to the ketones. A range of synthetic transformations of the resulting products are demonstrated as well.

Secular changes in eruption of primary teeth in Chinese infants and young children from three national cross-sectional surveys.

The eruption of primary teeth is a basic event during physical development of children, which is affected by heredity and environment. This study aimed to analyze the changes in primary teeth eruption among Chinese children with social development. A total of 249,264 healthy children under 2 years were extracted from the 1995, 2005, and 2015 National Survey on the Physical Growth and Development of Children in Nine Cities of China. Their primary teeth were examined and percentiles of primary teeth eruption age were calculated by probit analysis. The median primary teeth eruption age were 6.8 months, 6.7 months, 6.6 months in 1995, 2005 and 2015. Primary teeth eruption age of boys was 0.2 months, 0.3 months, 0.3 months earlier than that of girls in 1995, 2005 and 2015. Primary teeth eruption age was the earliest in children from northern region and was the latest in children from southern region, and this regional difference did not change over time. These findings suggest that primary teeth eruption age slightly advanced with social development, and their gender difference and regional difference have always existed, which supplied some data for understanding the secular trend of primary teeth development in stomatology, pediatrics, anthropology, and other related fields.

First Report of Powdery Mildew Caused by Podosphaera xanthii on Acalypha indica in China.

Acalypha indica L. is an annual erect herb of the Euphorbiaceae family. This plant is found widely in the tropics and parts of Africa and Asia (Chakraborty et al. 2023). In China, A. indica is a vegetable and also used as a folk medicine due to its antipyretic and hemostatic, antibacterial and anti-inflammatory properties. In February 2022 and 2023, powdery mildew symptoms were observed on 70% of A. indica plants on the Hainan Medical University campus (19° 58' 53″ N; 110° 19' 47″ E) in Haikou, Hainan Province, China. Powdery mildew colonies covered the leaf surfaces and stems of affected plants, causing discoloration and defoliation. Mycelia were superficial and hyphal appressoria were nipple-shaped. Conidiophores (n =30) were unbranched, cylindrical, 66 to 150 × 10 to 15 µm, and produced three to five immature conidia in chains with a crenate outline. Foot cells (n =30) were cylindrical, straight or sometimes curved at the base, and 31 to 59 µm long. Conidia (n =100) were ellipsoid-ovoid to doliiform, 20 to 33 ×12 to 20 µm (length/width ratio = 1.3 to 2.4), with well-developed fibrosin bodies, and produced germ tubes from the lateral position. Based on these morphological characteristics, the pathogen was provisionally identified as Podosphaera xanthii (Braun and Cook 2012). The teleomorph was not observed. A specimen was deposited in the Hainan Medical University Plant Pathology Herbarium as HMAI-23. To confirm the genus identification and ascertain a putative species, genomic DNA was extracted from mycelium, conidiophores, and conidia using a fungal DNA kit (Omega Bio-Tek, USA). The rDNA internal transcribed spacer (ITS) region was amplified with primers ITS1/ITS4 (White et al. 1990) and sequenced directly. The resulting 575-bp sequence was deposited in GenBank (accession no. OR775733). A BLASTn search in GenBank of this sequence showed 99% similarity with the ITS sequences of P. xanthii on plants of Fabaceae, Malvaceae and Cucurbitaceae family from China (MH143485, MT242593, MK439611 and MH143483), Thailand (LC270779 and LC270778), Korea (MG754404), Vietnam (KM260704), and Puerto Rico (OP882310). Additionally, the 28S rDNA region was amplified using the primer pairs NL1 and NL4 (O´Donnell 1993; accession no. OR784547). This region shared 99% similarity with P. xanthii isolates (LC371333, LC270780, AB936277, and OP765401) as well. To confirm pathogenicity, five healthy potted plants of A. indica were inoculated by gently pressing a powdery mildew-infected leaf onto 15 young leaves. Five non-inoculated plants served as controls. All plants were maintained in a greenhouse at 24 to 30°C, 70% relative humidity, with a 16-h photoperiod. After 7 days, inoculated leaves showed powdery mildew symptoms whereas no symptoms were observed on control plants. The fungal colonies observed on inoculated plants were morphologically identical to those found on the originally infected leaves collected from Hainan Province. Based on the morphological characteristics and molecular identification, the fungus was identified as P. xanthii. In different countries and regions, P. xanthii has been previously reported on A. indica from Sudan and India (Amano 1986). To our knowledge, this is the first record of P. xanthii infecting A. indica in China. We are concerned that the pathogen could become a threat to the widespread planting of A. indica in the future.

The RNA-binding domain of DCL3 is required for long-distance RNAi signaling.

Small RNA (sRNA)-mediated RNA silencing (also known as RNA interference, or RNAi) is a conserved mechanism in eukaryotes that includes RNA degradation, DNA methylation, heterochromatin formation and protein translation repression. In plants, sRNAs can move either cell-to-cell or systemically, thereby acting as mobile silencing signals to trigger noncell autonomous silencing. However, whether and what proteins are also involved in noncell autonomous silencing have not been elucidated. In this study, we utilized a previously reported inducible RNAi plant, PDSi, which can induce systemic silencing of the endogenous PDS gene, and we demonstrated that DCL3 is involved in systemic PDS silencing through its RNA binding activity. We confirmed that the C-terminus of DCL3, including the predicted RNA-binding domain, is capable of binding short RNAs. Mutations affecting RNA binding, but not processing activity, reduced systemic PDS silencing, indicating that DCL3 binding to RNAs is required for the induction of systemic silencing. Cucumber mosaic virus infection assays showed that the RNA-binding activity of DCL3 is required for antiviral RNAi in systemically noninoculated leaves. Our findings demonstrate that DCL3 acts as a signaling agent involved in noncell autonomous silencing and an antiviral effect in addition to its previously known function in the generation of 24-nucleotide sRNAs. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00124-6.

Autosomal recessive primary microcephaly type 2 associated with a novel WDR62 splicing variant that disrupts the expression of the functional transcript.

Background: Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized primarily by congenital microcephaly and intellectual disability but without extra-central nervous system malformations. This investigation aimed to elucidate the genetic underpinnings of microcephaly in a patient from a Chinese consanguineous family. Methods: A comprehensive clinical assessment, including brain magnetic resonance imaging (MRI), electroencephalogram (EEG), and genetic analyses, was conducted to evaluate the patient's condition. Whole-exome sequencing (WES) was employed to identify the causative gene, followed by Sanger sequencing, to confirm the mutation and its segregation within the family. Reverse transcript polymerase chain reaction (RT-PCR) was utilized to detect changes in splicing. Western blot was employed to reveal the difference of protein expression level between the wild-type and mutant WDR62 in vitro. Results: The patient exhibited classic MCPH symptoms, including microcephaly, recurrent epilepsy, delayed psychomotor development, and intellectual disability. Additionally, asymmetrical limb length was noted as a prominent feature. MRI findings indicated reduced brain volume with cortical malformations, while EEG demonstrated heightened sharp wave activity. A molecular analysis uncovered a novel homozygous variant c.4154-6 C > G in the WDR62 intron, and a functional analysis confirmed the pathogenicity of this mutation, resulting in the formation of an abnormal transcript with premature termination codons. Conclusion: This study enhances our understanding of the genetic heterogeneity associated with MCPH and highlights the pivotal role of genetic testing in the diagnosing and managing of rare neurodevelopmental disorders. Furthermore, it highlights the potential of emerging genetic therapies in treating conditions such as MCPH2.