First Report of Anthracnose on Wurfbainia villosa var. villosa Caused by Colletotrichum gloeosporioides in China.

Wurfbainia villosa var. villosa is a traditional Chinese herbal medicine under the family Zingiberaceae, and its ripe fruits (called Fructus Amomi) are widely used clinically for the treatment of gastrointestinal disorders (Yang et al. 2023; Chen et al. 2023). In September 2023, plants of W. villosa var. villosa exhibited anthracnose-like symptoms on leaf with a disease incidence of 35% (n = 100 investigated plants) in an approximately 90 m2 field in Guangning, China (N23°42'51.70″, E112°26'35.75″). Light yellowish-green spots (~2 mm diameter) initially appeared on the infected leaves, gradually formed sub-circular or irregular spots, then fused and expanded, resulting in wilting of the leaves. To identify the causal agent, 10 symptomatic leaves were collected and transferred to the laboratory. The symptomatic leaf samples were surface sterilized in 0.5% NaClO for 2 min, and in 70% ethanol for 30 s, then washed three times with sterile water and air-dried on sterile filter paper. The leaf tissues were placed on potato dextrose agar (PDA) medium containing 100 µg mL-1 of ampicillin (Sigma-Aldrich, St. Louis, MO) and incubated for 7 days at 28°C in darkness. Nine isolates with similar colony morphology were isolated from the 10 plated leaves. Three representative isolates (GNAF03, GNAF06, GNAF09 with approximately 3.5 cm in diameter after 3 days of incubation) appeared gray to dark brown with dense aerial hyphae at the front and gray to black colonies on the reverse of the plates. Conidia were cylindrical and measured 21.2 to 29.3 µm long × 7.1 to 9.6 µm wide (n = 50). Appressoria were formed by the tips of germ tubes or hyphae and were brown, ellipsoid, thick-walled, and smooth-margined, measuring 10.2 to 12.3 µm long × 6.4 to 8.2 µm wide (n = 50). Morphologically, the fungal isolates resembled Colletotrichum sp. (Weir et al. 2012). For molecular analysis, genomic DNA was extracted from fresh mycelia of the three isolates, and the primers ACT-512F/ACT-783R, CL1/CL2A, GDF/GDR, and ITS1/ITS4 were used to amplify partial regions of rDNA-ITS, actin (ACT), calmodulin (CAL), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) regions, respectively (Weir et al. 2012). The resulting sequences with more than 99% nucleotide identity to C. gloeosporioides were submitted to GenBank (accession numbers PP552725, PP552726, and OR827444 for ACT; PP552727, PP552728, and OR827443 for CAL; PP552729, PP552730, and OR827445 for GAPDH; PP549996, PP549999, and OR841394 for ITS). A phylogenetic tree was generated by the maximum likelihood method using the concatenated sequences of ACT, CAL, GADPH, and ITS by Polysuite software (Damm et al. 2020). Based on morphological and molecular analysis, the three isolates were characterized as C. gloeosporioides. The pathogenicity of the GNAF09 isolate was assessed on W. villosa var. villosa seedling leaves inoculated by spraying with 40 µL of conidial suspension at 106 conidia mL-1 or wounded with a sterile toothpick then inoculated with mycelial agar plugs (5 mm diameter). Control leaves were inoculated with 40 µL of sterile distilled water or agar plugs without mycelia. The inoculated plants were placed in a humid chamber at 28°C with 80% humidity and a 12 h light-dark photoperiod. Symptoms similar to those seen on naturally infected leaves were observed on all inoculated leaves after 7 days inoculation. Re-isolation was performed from 80% of the inoculated leaves and isolates were confirmed as C. gloeosporioides morphologically, confirming Koch's postulates, and by sequencing the ACT, CAL, GADPH, and ITS regions. The control groups remained asymptomatic. In previous studies, C. gloeosporioides has also caused anthracnose on Chinese medicinal plants, including Baishao (Radix paeoniae alba) (Zhang et al. 2017) and Rubia cordifolia L. (Tang et al. 2020). To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on W. villosa var. villosa in China. The results of our report serve as valuable references for further research on this disease.

Genome-wide evolutionary analysis of TKL_CTR1-DRK-2 gene family and functional characterization reveals that TaCTR1 positively regulates flowering time in wheat.

BACKGROUND: Flowering time has an important effect on regional adaptation and yields for crops. The tyrosine kinase-like (TKL) gene family is widely existed and participates in many biological processes in plants. Furthermore, only few TKLs have been characterized functions in controlling flowering time in wheat. RESULTS: Here, we report that TaCTR1, a tyrosine kinase-like (TKL) gene, regulates flowering time in wheat. Based on identification and evolutionary analysis of TKL_CTR1-DRK-2 subfamily in 15 plants, we proposed an evolutionary model for TaCTR1, suggesting that occurrence of some exon fusion events during evolution. The overexpression of TaCTR1 caused early flowering time in transgenic lines. Transcriptomics analysis enabled identification of mass differential expression genes including plant hormone (ET, ABA, IAA, BR) signaling, flavonoid biosynthesis, phenolamides and antioxidant, and flowering-related genes in TaCTR1 overexpression transgenic lines compared with WT plants. qRT-PCR results showed that the expression levels of ethylene (ET) signal-related genes (ETR, EIN, ERF) and flowering-related genes (FT, PPD1, CO, PRR, PHY) were altered in TaCTR1-overexpressing wheat compared with WT plants. Metabonomics analysis showed that flavonoid contents were altered. CONCLUSIONS: Thus, the results show that TaCTR1 plays a positive role in controlling flowering time by activating various signaling pathways and regulating flowering-related genes, and will provide new insights on the mechanisms of wheat flowering regulation.

Polyphenolic Nanoparticle-Modified Probiotics for Microenvironment Remodeling and Targeted Therapy of Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs) refer to multifaceted disorders in the intestinal microenvironment and microbiota homeostasis. In view of the broad bioactivity and high compatibility of polyphenols, there is considerable interest in developing a polyphenol-based collaborative platform to remodel the IBD microenvironment and regulate microbiota. Here, we demonstrated the coordination assembly of nanostructured polyphenols to modify probiotics and simultaneously deliver drugs for IBD treatment. Inspired by the distinctive structure of tannic acid (TA), we fabricated nanostructured pBDT-TA by using a self-polymerizable aromatic dithiol (BDT) and TA, which exhibited excellent antioxidant and anti-inflammatory capability in vitro. We thus coated pBDT-TA and sodium alginate (SA) to the surface of Escherichia coli Nissle 1917 layer by layer to construct the collaborative platform EcN@SA-pBDT-TA. The modified probiotics showed improved resistance to oxidative and inflammatory stress, which resulted in superior colon accumulation and retention in IBD model mice. Further, EcN@SA-pBDT-TA could alleviate dextran sulfate sodium (DSS)-induced colitis by controlling the inflammatory response, repairing intestinal barriers, and modulating gut microbiota. Importantly, EcN@SA-pBDT-TA-mediated IBD drug delivery could achieve an improved therapeutic effect in DSS model mice. Given the availability and functionality of polyphenol and prebiotics, we expected that nanostructured polyphenol-modified probiotics provided a solution to develop a collaborative platform for IBD treatment.

Repair of schneiderian membrane perforation through membrane fixation with simultaneous implant placement: a case report.

Perforation of the maxillary sinus membrane is a common complication during maxillary sinus elevation. Intraoperative perforation of the maxillary sinus membrane may complicate the procedure and indirectly lead to implant failure. Timely repair of the perforated maxillary sinus membrane can effectively improve the implant survival rate. This case describes a method of repairing a maxillary sinus membrane perforation with a suture-attached collagen membrane and shows stable repair results at a 31-month follow-up.

The complete chloroplast genome sequence and phylogenetic analysis of the Bichetii grass Chlorophytum laxum (Asparagaceae).

Chlorophytum laxum of Asparagaceae is a valuable ornamental plant native to the tropical regions of Asia, Africa, and Australia. The plant also has medicinal properties and is used as source for folk medicine. Despite being commercially important, genetic studies of C. laxum are still limited. To expand the genomic information of this plant species, we sequenced, assembled, and characterized its complete chloroplast genome. The chloroplast genome was 153,678 bp in length, with a large single-copy region (83,225 bp) and a small single-copy region (18,031 bp) separated by a pair of inverted repeat regions (26,211 bp each). A total of 127 genes were predicted, including 81 protein-coding, 38 tRNA, and eight rRNA genes. The overall GC content was 37.3%. Based on current sampling size, phylogenetic analysis using the maximum likelihood based on the complete chloroplast genome sequence revealed that the relationship in Chlorophytum is well resolved; C. laxum was closely related to C. rhizopendulum.

Distribution of mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes variants associated with hearing loss in Southwestern China.

BACKGROUND: Maternally inherited hearing loss has been associated with mitochondrial genes, including MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE. Among these genes, MT-RNR1 is known to be a hotspot for pathogenic variants related to aminoglycoside ototoxicity and nonsyndromic hearing loss. However, the frequency and spectrum of variants in these genes, particularly in multi-ethnic hearing loss patients from Southwestern China, are still not fully understood. METHODS: In this study, we enrolled 460 hearing loss patients from various ethnic backgrounds (Han, Yi, Dai, Hani, etc.) in Southwestern China. Next-generation sequencing was used to analyze the mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes. Subsequently, bioinformatical methods were employed to evaluate the identified variants. RESULTS: Among the patients with hearing loss, we identified 70 variants in MT-RNR1 (78.6 %, 55/70), MT-TL1 (4.3 %, 3/70), MT-TS1 (4.3 %, 3/70), MT-TK (7.1 %, 5/70) and MT-TE (5.7 %, 4/70) genes. We found that 15 variants were associated with hearing loss, including m.1555 A > G and m.1095 T > C. Additionally, we discovered three reported mitochondrial variants (m.676 G > A, m.7465 insC, and m.7474 A > G) newly correlated with hearing loss. Notably, certain pathogenic variants, such as m.1555 A > G, displayed non-consistent distributions among the multi-ethnic patients with hearing loss. Furthermore, the number of variants associated with hearing loss was higher in the Sinitic group (n = 181) and Tibeto-Burman group (n = 215) compared to the Kra-Dai group (n = 38) and Hmong-Mien group (n = 26). CONCLUSIONS: This present study revealed the distribution of mitochondrial variants linked to hearing loss across various ethnic groups in Southwestern China. These data suggest a potential correlation between the distribution of mitochondrial variants associated with hearing loss and ethnic genetic backgrounds.

Structural and functional brain alterations in subthreshold depression: A multimodal coordinate-based meta-analysis.

Imaging studies of subthreshold depression (StD) have reported structural and functional abnormalities in a variety of spatially diverse brain regions. However, there is no consensus among different studies. In the present study, we applied a multimodal meta-analytic approach, the Activation Likelihood Estimation (ALE), to test the hypothesis that StD exhibits spatially convergent structural and functional brain abnormalities compared to healthy controls. A total of 31 articles with 25 experiments were included, collectively representing 1001 subjects with StD. We found consistent differences between StD and healthy controls mainly in the left insula across studies with various neuroimaging methods. Further exploratory analyses found structural atrophy and decreased functional activities in the right pallidum and thalamus in StD, and abnormal spontaneous activity converged to the middle frontal gyrus. Coordinate-based meta-analysis found spatially convergent structural and functional impairments in StD. These findings provide novel insights for understanding the neural underpinnings of subthreshold depression and enlighten the potential targets for its early screening and therapeutic interventions in the future.

First report of Neocosmospora pisi causing blight on Ammopiptanthus mongolicus in China.

Ammopiptanthus mongolicus is the only evergreen broad-leaved shrub in the desert region of Northwest China, which is one of the dominant species in the desert vegetation of the region, playing an important role in maintaining the stability of the local desert ecosystem. A. mongolicus is also very hardy and drought resistant and can survive extreme temperatures (Liu et al. 2013; Yang et al. 2022). The large-scale death of A. mongolicus could cause desertification in the region. Two months after the discovery of Fusarium verticillioides causing blight on A. mongolicus in Etuoke county, Inner Mongolia Autonomous Region in September 2023 (Yang et al. 2024), a large number of A. mongolicus plants with symptoms of blights were found in Lingwu city, Ningxia Hui Autonomous Region, China (106.442368°E, 37.734026°N) in November 2023. The incidence of diseased plants in this field was about 30%. The field symptoms in Lingwu city were similar to those observed in Etuoke county. The diseased leaves initially turned yellow, then wilted and dehisced, eventually resulting in plant death (Figure 1). The roots of the diseased plants were cut diagonally and the central cylinder showed a brown color (Figure 2). In order to investigate whether the death of A. mongolicus was caused by the same pathogen as those identified previously, 30 roots were collected from 10 diseased plants. After rinsing and surface sterilization (70% ethanol for 3 min and 2.5% NaClO for 5 min, rinsed 3 times with sterile distilled water), diseased tissues (10×10 mm) were placed on potato dextrose agar (PDA) (3 pieces per plate) and incubated from 3 to 5 days at 25°C. The strain AmP5 was isolated and used for further study. After 3 days on PDA medium, fungal colonies were white to milky, the undersides of the cultures were yellowish to orange-brown (Figure 3). After 7 days on synthetic nutrient-poor agar (SNA), microconidia were ovoidal or with a rounded apex and truncate base, 10.5 ± 1.5 µm × 1.6 ± 0.2 µm (×400). The macroconidia were slightly curved or arcuate, 40.5 ± 3.5 µm × 5 ± 0.5 µm (×400) (Figure 4) (Sisic et al. 2018). The pathogen was confirmed to be Neocosmospora pisi by multigene phylogenetic analysis of TEF, RPB1 and RPB2 genes using primers EF1/EF2, F5/G2R and 5F2/11AR, respectively (O'Donnell et al. 2022). The sequences of PCR products were deposited in GenBank with accession numbers OR944631 (RPB1), OR988086 (TEF) and OR988087 (RPB2), respectively. The results of pairwise alignment in Fusarioid-ID database (Crous et al. 2021) showed 99.84% similarity and 83.96% overlap of the EF1-α sequence to the corresponding sequence LR583636 of ex-epitype CBS 123669 of Neocosmospora pisi (syn. Fusarium solani f. sp. pisi), 99.72% similarity and 85.66% overlap of the RPB1 sequence to the corresponding sequence MW834242 of ex-epitype CBS 123669 of N. pisi, and 99.47% similarity and 78.26% overlap of RPB2 sequence to the corresponding sequence LR583862 of ex-epitype CBS 123669 of N. pisi. Moreover, the result of polyphasic identification in the Fusarioid-ID database also showed EF1-a, RPB1, and RPB2 sequences had 99.15% similarity to the corresponding sequences of CBS 1233669. The pathogenicity of AmP5 was tested on potted 64 days old seedlings A. mongolicus plants. The roots of 3 seedlings were inoculated with conidial suspension (1×106 /ml), and another 3 used as controls were inoculated with sterile water, by gently peeling off the soil around the roots during inoculation, and pouring the conidial suspension around the roots (10 ml/seedling). All plants were placed in a growth chamber at 18-25℃ (10 h light; 14 h dark). After incubation for 3-5 days, the symptoms similar to those observed in the field (Figure 5), including brown rot of steles (Figure 6), developed on plants inoculated with conidial suspension, whereas no symptoms were observed on the control plants. The same pathogen was reisolated from inoculated roots and confirmed as N. pisi based on morphological and molecular analyses (TEF, RPB1 and RPB2). To our knowledge, this is the first report of blight on A. mongolicus caused by N. pisi in China. This study also indicates that blight on A. mongolicus can be caused by different fungal pathogens. Blight caused by different pathogens may have different in terms of control measures and pathogenic mechanisms, so the study of blight caused by different pathogens is of profound value.

Alcohol-Processable All-Polymer n-Type Thermoelectrics.

The general strategy for n-type organic thermoelectric is to blend n-type conjugated polymer hosts with small molecule dopants. In this work, all-polymer n-type thermoelectric is reported by dissolving a novel n-type conjugated polymer and a polymer dopant, poly(ethyleneimine) (PEI), in alcohol solution, followed by spin-coating to give polymer host/polymer dopant blend film. To this end, an alcohol-soluble n-type conjugated polymer is developed by attaching polar and branched oligo (ethylene glycol) (OEG) side chains to a cyano-substituted poly(thiophene-alt-co-thiazole) main chain. The main chain results in the n-type property and the OEG side chain leads to the solubility in hexafluorineisopropanol (HFIP). In the polymer host/polymer dopant blend film, the Coulombic interaction between the dopant counterions and the negatively charged polymer chains is reduced and the ordered stacking of the polymer host is preserved. As a result, the polymer host/polymer dopant blend exhibits the power factor of 36.9 µW m-1 K-1, which is one time higher than that of the control polymer host/small molecule dopant blend. Moreover, the polymer host/polymer dopant blend shows much better thermal stability than the control polymer host/small molecule dopant blend. This research demonstrates the high performance and excellent stability of all-polymer n-type thermoelectric.

Zinc finger protein 36 like 2-histone deacetylase 1 axis is involved in the bone responses to mechanical stress.

The molecular mechanism underlying the promotion of fracture healing by mechanical stimuli remains unclear. The present study aimed to investigate the role of zinc finger protein 36 like 2 (ZFP36L2)-histone deacetylase 1 (HDAC1) axis on the osteogenic responses to moderate mechanical stimulation. Appropriate stimulation of fluid shear stress (FSS) was performed on MC3T3-E1 cells transduced with ZFP36L2 and HDAC1 recombinant adenoviruses, aiming to validate the influence of mechanical stress on the expression of ZFP36L2-HDAC1 and the osteogenic differentiation and mineralization. The results showed that moderate FSS stimulation significantly upregulated the expression of ZFP36L2 in MC3T3-E1 cells (p < 0.01). The overexpression of ZFP36L1 markedly enhanced the levels of osteogenic differentiation markers, including bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), Osterix, and collagen type I alpha 1 (COL1A1) (p < 0.01). ZFP36L2 accelerated the degradation of HDAC1 by specifically binding to its 3' UTR region, thereby fulfilling its function at the post-transcriptional regulatory gene level and promoting the osteogenic differentiation and mineralization fate of cells. Mechanical unloading notably diminished/elevated the expression of ZFP36L2/HDAC1, decreased bone mineral density and bone volume fraction, hindered the release of osteogenic-related factors and vascular endothelial growth factor in callus tissue (p < 0.01), and was detrimental to fracture healing. Collectively, proper stress stimulation plays a crucial role in facilitating osteogenesis through the promotion of ZFP36L2 and subsequent degradation of HDAC1. Targeting ZFP36L2-HDAC1 axis may provide promising insights to enhance bone defect healing.

Temporal and Within-Sporophyte Variations in Triphenyltin Chloride (TPTCL) and Its Degradation Products in Cultivated Undaria pinnatifida.

Undaria pinnatifida can effectively deal with organotin pollution through its excellent accumulation and degradation capabilities found under laboratory conditions. However, nothing is known regarding its accumulation, degradation performance, and related impact factors in the wild farming area. In this study, we monitored triphenyltin chloride (TPTCL) contents and degradation products in different algal parts (blades, stipes, sporophylls, and holdfasts) of cultivated U. pinnatifida from December 2018 to May 2019. Our results showed that sporophytes had an accumulation and degradation capacity for TPTCL. The TPTCL contents and degradation products varied with the algal growth stages and algal parts. TPTCL accumulated in the blades at the growth stage and the blades, stipes, sporophylls, and holdfasts at the mature stage. The TPTCL content among algal parts was blades (74.92 ± 2.52 µg kg-1) > holdfasts (62.59 ± 1.42 µg kg-1) > sporophylls (47.24 ± 1.41 µg kg-1) > stipes (35.53 ± 0.55 µg kg-1). The primary degradation product DPTCL accumulated only in the blades at any stage, with a concentration of 69.30 ± 3.89 µg kg-1. The secondary degradation product MPTCL accumulated in the blades at the growth stage and in the blades, stipe, and sporophyll at the mature stage. The MPTCL content among algal parts was blades (52.80 ± 3.48 µg kg-1) > sporophylls (31.08 ± 1.53 µg kg-1) > stipes (20.44 ± 0.85 µg kg-1). The accumulation pattern of TPTCL and its degradation products seems closely related to nutrient allocation in U. pinnatifida. These results provide the basis for applying cultivated U. pinnatifida in the bioremediation of organotin pollution and the food safety evaluation of edible algae.

Novel PLCZ1 mutation caused polyspermy during in vitro fertilization.

ABSTRACT: Failure of oocyte activation, including polyspermy and defects in pronuclear (PN) formation, triggers early embryonic developmental arrest. Many studies have shown that phospholipase C zeta 1 ( PLCZ1 ) mutations cause failure of PN formation following intracytoplasmic sperm injection (ICSI); however, whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization (IVF) remains unknown. Whole-exome sequencing (WES) was performed to identify candidate mutations in couples with primary infertility. Sanger sequencing was used to validate the mutations. Multiple PLCZ1 -mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced. Assisted oocyte activation (AOA) after ICSI was performed to overcome the failure of oocyte activation. We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles, including a novel missense mutation c.1154C>T, p.R385Q. PN formation failure was observed during the ICSI cycle. However, injection of multiple PLCZ1 -mutated sperm induced PN formation, suggesting that the Ca 2+ oscillations induced by the sperm exceeded the necessary threshold for PN formation. AOA after ICSI enabled normal fertilization, and all patients achieved successful pregnancies. These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy. Furthermore, this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

Image detection of aortic dissection complications based on multi-scale feature fusion.

Background: Aortic dissection refers to the true and false two-lumen separation of the aortic wall, in which the blood in the aortic lumen enters the aortic mesomembrane from the tear of the aortic intima to separate the mesomembrane and expand along the long axis of the aorta. Purpose: In view of the problems of individual differences, complex complications and many small targets in clinical aortic dissection detection, this paper proposes a convolution neural network MFF-FPN (Multi-scale Feature Fusion based Feature Pyramid Network) for the detection of aortic dissection complications. Methods: The proposed model uses Resnet50 as the backbone for feature extraction and builds a pyramid structure to fuse low-level and high-level feature information. We add an attention mechanism to the backbone network, which can establish inter-dependencies between feature graph channels and enhance the representation quality of CNN. Results: The proposed method has a mean average precision (MAP) of 99.40% in the task of multi object detection for aortic dissection and complications, which is higher than the accuracy of 96.3% on SSD model and 99.05% on YoloV7 model. It greatly improves the accuracy of small target detection such as cysts, making it more suitable for clinical focus detection. Conclusions: The proposed deep learning model achieves feature reuse and focuses on local important information. By adding only a small number of model parameters, we are able to greatly improve the detection accuracy, which is effective in detecting small target lesions commonly found in clinical settings, and also performs well on other medical and natural datasets.

Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction.

Novel CHCHD2 mutations causing C-terminal truncation and interrupted CHCHD2 protein stability in Parkinson's disease (PD) patients were previously found. However, there is limited understanding of the underlying mechanism and impact of subsequent CHCHD2 loss-of-function on PD pathogenesis. The current study further identified the crucial motif (aa125-133) responsible for diminished CHCHD2 expression and the molecular interplay within the C1QBP/CHCHD2/CHCHD10 complex to regulate mitochondrial functions. Specifically, CHCHD2 deficiency led to decreased neural cell viability and mitochondrial structural and functional impairments, paralleling the upregulation of autophagy under cellular stresses. Meanwhile, as a binding partner of CHCHD2, C1QBP was found to regulate the stability of CHCHD2 and CHCHD10 proteins to maintain the integrity of the C1QBP/CHCHD2/CHCHD10 complex. Moreover, C1QBP-silenced neural cells displayed severe cell death phenotype along with mitochondrial damage that initiated a significant mitophagy process. Taken together, the evidence obtained from our in vitro and in vivo studies emphasized the critical role of CHCHD2 in regulating mitochondria functions via coordination among CHCHD2, CHCHD10, and C1QBP, suggesting the potential mechanism by which CHCHD2 function loss takes part in the progression of neurodegenerative diseases.

Extensive Stage Small-Cell Lung Cancer with Cystic Brain Metastases: A Report of Two Cases.

Objective: Cystic brain metastases (BMs) are rare in small cell lung cancer (SCLC), and there are limited data on the treatment and prognosis of cystic BMs. Whole brain radiotherapy has been the mainstay for BMs since several years. Immune checkpoint inhibitors in extensive stage small cell lung cancer (ES-SCLC) have been shown to be suitable for patients who experienced better overall survival and progress-free survival and have been approved as the first-line treatment for ES-SCLC. In this report, we described two ES-SCLC patients developed cystic BMs after immunotherapy, after which the patients continued to treat the primary lesion with immune checkpoint inhibitors and the cystic BMs with radiotherapy. Case Description: Two male patients were diagnosed with ES-SCLC at the first admission and were subsequently treated with immunotherapy plus platinum therapy, during which cystic BMs developed. One patient received whole brain radiotherapy and the other received whole brain radiotherapy and Gamma knife radiosurgery (GKRS). Immunotherapy was continued after the brain lesions were controlled. It has been 33 months since the first patient was diagnosed and is now in stable condition. The other patient achieved an overall survival of 30 months. Conclusion: This report describes two patients with cystic brain metastases in ES-SCLC. Whole brain radiotherapy has a good effect on local control of cystic brain metastases in small cell lung cancer and can significantly improve the symptoms of patients. At the same time, we treat immunotherapy as the first-line treatment, and then perform cross-immunotherapy after disease progression, combined with anti-vascular targeting drugs. The patient did not develop severe iRAEs.

PLD1 promotes spindle assembly and migration through regulating autophagy in mouse oocyte meiosis.

PLD1 has been implicated in cytoskeletal reorganization and vesicle trafficking in somatic cells; however, its function remains unclear in oocyte meiosis. Herein, we found PLD1 stably expresses in mouse oocytes meiosis, with direct interaction with spindle, RAB11A+ vesicles and macroautophagic/autophagic vacuoles. The genetic or chemical inhibition of PLD1 disturbed MTOC clustering, spindle assembly and its cortical migration, also decreased PtdIns(4,5)P2, phosphorylated CFL1 (p-CFL1 [Ser3]) and ACTR2, and their local distribution on MTOC, spindle and vesicles. Furthermore in PLD1-suppressed oocytes, vesicle size was significantly reduced while F-actin density was dramatically increased in the cytoplasm, the asymmetric distribution of autophagic vacuoles was broken and the whole autophagic process was substantially enhanced, as illustrated with characteristic changes in autophagosomes, autolysosome formation and levels of ATG5, BECN1, LC3-II, SQSTM1 and UB. Exogenous administration of PtdIns(4,5)P2 or overexpression of CFL1 hyperphosphorylation mutant (CFL1S3E) could significantly improve polar MTOC focusing and spindle structure in PLD1-depleted oocytes, whereas overexpression of ACTR2 could rescue not only MTOC clustering, and spindle assembly but also its asymmetric positioning. Interestingly, autophagy activation induced similar defects in spindle structure and positioning; instead, its inhibition alleviated the alterations in PLD1-depleted oocytes, and this was highly attributed to the restored levels of PtdIns(4,5)P2, ACTR2 and p-CFL1 (Ser3). Together, PLD1 promotes spindle assembly and migration in oocyte meiosis, by maintaining rational levels of ACTR2, PtdIns(4,5)P2 and p-CFL1 (Ser3) in a manner of modulating autophagy flux. This study for the first time introduces a unique perspective on autophagic activity and function in oocyte meiotic development.Abbreviations: ACTR2/ARP2: actin related protein 2; ACTR3/ARP3: actin related protein 3; ATG5: autophagy related 5; Baf-A1: bafilomycin A1; BFA: brefeldin A; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GOLGA2/GM130: golgin A2; GV: germinal vesicle; GVBD: germinal vesicle breakdown; IVM: in vitro maturation; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MI: metaphase of meiosis I; MII: metaphase of meiosis II; MO: morpholino; MTOC: microtubule-organizing center; MTOR: mechanistic target of rapamycin kinase; PB1: first polar body; PLA: proximity ligation assay; PLD1: phospholipase D1; PtdIns(4,5)P2/PIP2: phosphatidylinositol 4,5-bisphosphate; RAB11A: RAB11A, member RAS oncogene family; RPS6KB1/S6K1: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TUBA/α-tubulin: tubulin alpha; TUBG/γ-tubulin: tubulin gamma; UB: ubiquitin; WASL/N-WASP: WASP like actin nucleation promoting factor.

Nr5a2 ensures inner cell mass formation in mouse blastocyst.

Recent studies have elucidated Nr5a2's role in activating zygotic genes during early mouse embryonic development. Subsequent research, however, reveals that Nr5a2 is not critical for zygotic genome activation but is vital for the gene program between the 4- and 8-cell stages. A significant gap exists in experimental evidence regarding its function during the first lineage differentiation's pivotal period. In this study, we observed that approximately 20% of embryos developed to the blastocyst stage following Nr5a2 ablation. However, these blastocysts lacked inner cell mass (ICM), highlighting Nr5a2's importance in first lineage differentiation. Mechanistically, using RNA sequencing and CUT&Tag, we found that Nr5a2 transcriptionally regulates ICM-specific genes, such as Oct4, to establish the pluripotent network. Interference with or overexpression of Nr5a2 in single blastomeres of 2-cell embryos can alter the fate of daughter cells. Our results indicate that Nr5a2 works as a doorkeeper to ensure ICM formation in mouse blastocyst.

Microbial diversity and their extracellular enzyme activities among different soil particle sizes in mossy biocrust under N limitation in the southeastern Tengger Desert, China.

Introduction: Mossy biocrust represents a stable stage in the succession of biological soil crust in arid and semi-arid areas, providing a microhabitat that maintains microbial diversity. However, the impact of mossy biocrust rhizoid soil and different particle sizes within the mossy biocrust layer and sublayer on microbial diversity and soil enzyme activities remains unclear. Methods: This study utilized Illumina MiSeq sequencing and high-throughput fluorometric technique to assess the differences in microbial diversity and soil extracellular enzymes between mossy biocrust rhizoid soil and different particle sizes within the mossy biocrust sifting and sublayer soil. Results: The results revealed that the total organic carbon (TOC), total nitrogen (TN), ammonium (NH4+) and nitrate (NO3-) in mossy biocrust rhizoid soil were the highest, with significantly higher TOC, TN, and total phosphorus (TP) in mossy biocrust sifting soil than those in mossy biocrust sublayer soil. Extracellular enzyme activities (EAAs) exhibited different responses to various soil particle sizes in mossy biocrust. Biocrust rhizoid soil (BRS) showed higher C-degrading enzyme activity and lower P-degrading enzyme activity, leading to a significant increase in enzyme C: P and N: P ratios. Mossy biocrust soils were all limited by microbial relative nitrogen while pronounced relative nitrogen limitation and microbial maximum relative carbon limitation in BRS. The diversity and richness of the bacterial community in the 0.2 mm mossy biocrust soil (BSS0.2) were notably lower than those in mossy biocrust sublayer, whereas the diversity and richness of the fungal community in the rhizoid soil were significantly higher than those in mossy biocrust sublayer. The predominant bacterial phyla in mossy biocrust were Actinobacteriota, Protebacteria, Chloroflexi, and Acidobacteriota, whereas in BSS0.2, the predominant bacterial phyla were Actinobacteriota, Protebacteria, and Cyanobacteria. Ascomycota and Basidiomycota were dominant phyla in mossy biocrust. The bacterial and fungal community species composition exhibited significant differences. The mean proportions of Actinobacteriota, Protebacteria, Chloroflexi, Acidobacteriota, Acidobacteria, Cyanobacteria, and Bacteroidota varied significantly between mossy biocrust rhizoid and different particle sizes of mossy biocrust sifting and sublayer soil (p < 0.05). Similarly, significant differences (p < 0.05) were observed in the mean proportions of Ascomycota, Basidiomycota, and Glomeromycota between mossy biocrust rhizoid and different particle sizes within the mossy biocrust sifting and sublayer soil. The complexity and connectivity of bacterial and fungal networks were higher in mossy biocrust rhizoid soil compared with different particle sizes within the mossy biocrust sifting and sublayer soil. Discussion: These results offer valuable insights to enhance our understanding of the involvement of mossy biocrust in the biogeochemical cycle of desert ecosystems.