[Separation/Conversion Disorders in Functional Coma With Pseudocataplexy: Report of One Case and Literature Review].

Separation/conversion disorders in functional coma with pseudocataplexy are rare.On December 9,2021,a young female patient with separation/conversion disorders was treated in the Department of Neurology in the First Affiliated Hospital of Shandong First Medical University.The main symptoms were episodic consciousness disorders,sudden fainting,and urinary incontinence.Complete laboratory tests and cranial magnetic resonance imaging showed no obvious abnormalities.Standard multi-channel sleep monitoring and multiple sleep latency tests were performed.The patient was unable to wake up during nap and underwent stimulation tests.There was no response to orbital pressure,loud calls,or tapping,while the α rhythm in all electroencephalogram leads and the increased muscular tone in the mandibular electromyography indicated a period of wakefulness.The results of 24-hour sleep monitoring suggested that the patient had sufficient sleep at night and thus was easy to wake up in the morning.The results of daytime unrestricted sleep and wake-up test showed that the patient took one nap in the morning and one nap in the afternoon.When the lead indicated the transition from N3 to N2 sleep,a wake-up test was performed on the patient.At this time,the patient reacted to the surrounding environment and answered questions correctly.Because the level of orexin in the cerebrospinal fluid was over 110 pg/mL,episodic sleep disorder was excluded and the case was diagnosed as functional coma accompanied by pseudocataplexy.The patient did not present obvious symptom remission after taking oral medication,and thus medication withdrawl was recommended.Meanwhile,the patient was introduced to adjust the daily routine and mood.The follow-up was conducted six months later,and the patient reported that she did not experience similar symptoms after adjusting lifestyle.Up to now,no similar symptoms have appeared in multiple follow-up visits for three years.Functional coma with pseudocataplexy is prone to misdiagnosis and needs to be distinguished from true coma and episodic sleep disorders.

Structural analysis of the mitochondrial genome of Santalum album reveals a complex branched configuration.

BACKGROUND: Santalum album L. is an evergreen tree which is mainly distributes throughout tropical and temperate regions. And it has a great medicinal and economic value. RESULTS: In this study, the complete mitochondrial genome of S. album were assembled and annotated, which could be described by a complex branched structure consisting of three contigs. The lengths of these three contigs are 165,122 bp, 93,430 bp and 92,491 bp. We annotated 34 genes coding for proteins (PCGs), 26 tRNA genes, and 4 rRNA genes. The analysis of repeated elements shows that there are 89 SSRs and 242 pairs of dispersed repeats in S. album mitochondrial genome. Also we found 20 MTPTs among the chloroplast and mitochondria. The 20 MTPTs sequences span a combined length of 22,353 bp, making up 15.52 % of the plastome, 6.37 % of the mitochondrial genome. Additionally, by using the Deepred-mt tool, we found 628 RNA editing sites in 34 PCGs. Moreover, significant genomic rearrangement is observed between S. album and its associated mitochondrial genomes. Finally, based on mitochondrial genome PCGs, we deduced the phylogenetic ties between S. album and other angiosperms. CONCLUSIONS: We reported the mitochondrial genome from Santalales for the first time, which provides a crucial genetic resource for our study of the evolution of mitochondrial genome.

Major pathologic response and long-term clinical benefit in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer after neoadjuvant chemotherapy.

BACKGROUND: The majority of HR+/HER2-breast cancer patients can also achieve long-term survival despite not attaining pCR, indicating limited prognostic value of pCR in this population. This study aimed to identify novel pathologic end points for predicting long-term outcomes in HR+/HER2-breast cancer after neoadjuvant chemotherapy. METHODS: We analyzed HR+/HER2-breast cancer patients with stage II-III tumors who underwent curative surgery after neoadjuvant chemotherapy from three hospitals. Major pathologic response (MPR), defined as the presence of Miller-Payne grades 3-5 and positive lymph node ratio of ≤10 %, was used as a pathological evaluation indicator. We assessed the association between MPR and event-free survival (EFS) and performed Multivariable Cox regression to identify independent factors associated with EFS. RESULTS: From January 2010 to December 2020, 386 patients were included in the final analysis. 28 patients (7.3 %) achieved pCR and 118 patients (30.6 %) achieved MPR. The median duration of follow-up was 54.4 months,5-year EFS was 87 % in the MPR group vs. 68 % in the non-MPR group. Multivariate analysis showed that low PR expression, high clinical stage, lower Miller-Payne grades and Positive lymph node ratio were independent poor prognostic factors for EFS (all P values < 0.05). The prognostic effect of MPR remained in multivariable models (hazard ratio (HR), 0.45; 95 % confidence interval (CI), 0.26-0.76; P = 0.008), In non-pCR patients, those who achieved MPR exhibited a similar EFS compared with pCR patients (HR, 2.25; 95 % CI, 0.51-9.84; P = 0.28). CONCLUSION: MPR may be a novel pathologic end point in HR+/HER2-breast cancer after neoadjuvant chemotherapy, holding greater applicability in the prognosis evaluation than pCR.

Solvent-Controlled Divergent Cyclization of 3-Ylideneoxindoles with Ethyl 2-Diazoacetate: Access to Spirocyclopropyl and Spiropyrazolines Oxindoles.

Herein a catalyst-free solvent-controlled method for the divergent synthesis of spirocyclopropyl and spiropyrazoline oxindoles from 3-ylideneoxindoles and ethyl diazoacetate was developed. With ClCH2CH2Cl as the solvent, spirocyclopropyl oxindoles were obtained in moderate to excellent yields, whereas the use of MeOH as solvent afforded spiropyrazoline oxindoles in moderate to good yields. The readily available substrates, simple operation and various product transformations further highlighted the utility of this method.

Tryptophan regulates the expression of IGFBP1 in bovine endometrial epithelial cells in vitro via the TDO2-AHR pathway.

BACKGROUND: This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells. RESULTS: Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1. CONCLUSIONS: The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.

Functional genomics and taxonomic insights into heavy metal tolerant novel bacterium Brevibacterium metallidurans sp. nov. NCCP-602T isolated from tannery effluent in Pakistan.

The strain designated NCCP-602T was isolated from tannery effluent, and displayed aerobic, gram-positive, rod-shaped cells that were characterized by oxidase negative, catalase positive, and non-motile features. The most favourable growth conditions were observed at a temperature of 30°C, pH 7.0, and NaCl concentration of 1% (w/v). It tolerated heavy metals at high concentrations of chromium (3600 ppm), copper (3300 ppm), cadmium (3000 ppm), arsenic (1200 ppm) and lead (1500 ppm). The results of phylogenetic analysis, derived from sequences of the 16S rRNA gene, indicated the position of strain NCCP-602T within genus Brevibacterium and showed that it was closely related to Brevibacterium ammoniilyticum JCM 17537T. Strain NCCP-602 T formed a robust branch that was clearly separate from closely related taxa. A comparison of 16S rRNA gene sequence similarity and dDDH values between the closely related type strains and strain NCCP-602T provided additional evidence supporting the classification of strain NCCP-602T as a distinct novel genospecies. The polar lipid profile included diphosphatidylglycerol, glycolipid, phospholipids and amino lipids. MK-7 and MK-8 were found as the respiratory quinones, while anteiso-C15:0, iso-C15:0, iso-C16:0, iso-C17:0, and anteiso-C17:0 were identified as the predominant cellular fatty acids (> 10%). Considering the convergence of phylogenetic, phenotypic, chemotaxonomic, and genotypic traits, it is suggested that strain NCCP-602 T be classified as a distinct species Brevibacterium metallidurans sp. nov. within genus Brevibacterium with type strain NCCP-602T (JCM 18882T = CGMCC1.62055T).

Block Copoly (Ester-Carbonate) Electrolytes for LiFePO4|Li Batteries with Stable Cycling Performance.

To address the challenges posed by the narrow oxidation decomposition potential window and the characteristic of low ionic conductivity at room temperature of solid polymer electrolytes (SPEs), carbon dioxide (CO2), epichlorohydrin (PO), caprolactone (CL), and phthalic anhydride (PA) were employed in synthesizing di-block copolymer PCL-b-PPC and PCL-b-PPCP. The carbonate and ester bonds in PPC and PCL provide high electrochemical stability, while the polyether segments in PPC contribute to the high ion conductivity. To further improve the ion conductivity, we added succinonitrile as a plasticizer to the copolymer and used the copolymer to assemble lithium metal batteries (LMBs) with LiFePO4 as the cathode. The LiFePO4/SPE/Li battery assembled with PCL-b-PPC electrolyte exhibited an initial discharge-specific capacity of 155.5 mAh·g-1 at 0.5 C and 60 °C. After 270 cycles, the discharge-specific capacity was 140.8 mAh·g-1, with a capacity retention of 90.5% and an average coulombic efficiency of 99%, exhibiting excellent electrochemical performance. The study establishes the design strategies of di-block polymer electrolytes and provides a new strategy for the application of LMBs.

Effects of prenatal stress on reproductive function of male offspring through the KISS1 system.

Prenatal stress can lead to the programming of the neuroendocrine system in male offspring, disrupting the hypothalamic testicular axis and adversely affecting the reproductive health of male offspring. This study aimed to determine the long-term effects of prenatal stress on the KISS1 system in male offspring and the effects on reproductive function in male offspring. Sixteen pregnant females were divided into a prenatal control group (PC,n=8) and a prenatal stress group (PS,n=8). The PS group was modeled with chronic unpredictable mild stress (CUMS) from day 1 of gestation to full-term delivery. Differences between the two groups in various maternal parameters, including glucocorticoid secretion, litter size, and the effects of male offspring birth weight, the KISS1 system, and reproductive function, were determined. Male offspring of PS dams had lower birth weights compared to prenatal controls.KISS1 gene expression is reduced at birth and in adult PS offspring, and its receptor KISS1-R protein is similarly reduced in PS offspring at birth and adulthood. In adulthood, PS male offspring show significantly reduced sex hormone production, altered testicular morphology, reduced maturation of their supporting cells, and decreased expression of connexin 43 (CX43), leading to an altered sperm microenvironment and reduced sperm quality. In conclusion, prenatal stress leads to adverse changes in the KISS1 system in male offspring and decreased reproductive function.

Chitosan/rutin multifunctional hydrogel with tunable adhesion, anti-inflammatory and antibacterial properties for skin wound healing.

Effective wound care remains a significant challenge due to the need for infection prevention, inflammation reduction, and minimal tissue damage during dressing changes. To tackle these issues, we have developed a multifunctional hydrogel (CHI/CPBA/RU), composed of chitosan (CHI) modified with 4-carboxyphenylboronic acid (CPBA) and the natural flavonoid, rutin (RU). This design endows the hydrogel with body temperature-responsive adhesion and low temperature-triggered detachment, thus enabling painless removal during dressing changes. The CHI/CPBA/RU hydrogels exhibit excellent biocompatibility, maintaining over 97 % viability of L929 cells. They also demonstrate potent intracellular free radical scavenging activity, with scavenging ratios ranging from 53 % to 70 %. Additionally, these hydrogels show anti-inflammatory effects by inhibiting pro-inflammatory cytokines (TNF-α, IL-6, and iNOS) and increasing anti-inflammatory markers (Arg1 and CD206) in RAW 264.7 macrophages. Notably, they possess robust antimicrobial properties, inhibiting over 99.9 % of the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus growth. In vivo testing on a murine full-thickness skin defect model shows that the hydrogel significantly accelerates wound healing by reducing inflammation, increasing collagen deposition, and promoting angiogenesis, achieving 98 % healing by day 10 compared to 78 % in the control group. These attributes make the polysaccharide-based hydrogel a promising material for advanced wound care.

Bibliometric analysis of Mongolian medicine and medicinal materials in China since 2000.

Aim of the study: To analyze the progress in Mongolian medicine and medicinal materials and to highlight its development process, emerging trends, and hotspots. Materials and methods: Papers on Mongolian medicine and medicinal materials from January 2000 to May 2022 were retrieved from the China National Knowledge Infrastructure (CNKI) database. Using the collaboration network analysis of CiteSpace V and VOSviewer software, the cooperation among individuals and institutions in the field of scientific research was analyzed. The functions of frequency analysis, cluster analysis, and burst analysis were employed to conduct bibliometric analysis on research hotspots and trends in the field of Mongolian medicine research. Furthermore, the data visualization function was utilized to clearly display data trends and changes. Results: A total of 8362 papers on Mongolian medicine medicinal materials from CNKI were identified and analyzed.The research on Mongolian medicine has gone through three stages: the initial stage, the exploratory stage, and the developmental stage. The top two institutions in the number of papers are Inner Mongolia Medical University and Inner Mongolia University for Nationalities. Bagenna from Inner Mongolia Medical University is the author with the most papers. "clinical efficacy", "clinical research", and "quality standards" were the most frequently used keywords. Research in the field of Mongolian medicine has focused on several diseases, including skeletal system disorders, cardiovascular diseases, and digestive system disorders. Conclusion: Since 2000, there have been growing attention and efforts made in the field of Mongolian medicine and medicinal materials. The research in the field of Mongolian medicine had undergone three stages, namely the initial stage, the exploratory stage, and the developmental stage. The focus shifted from basic research such as the analysis of medicinal ingredients in Mongolian herbs to the application-oriented directions of traditional treatment techniques and advantageous diseases in Mongolian medicine. To make breakthroughs in this field, further research is needed to improve the persuasiveness and authority of Mongolian medicine and medicinal materials in terms of mechanism, standardization, and safety, to promote the development of Mongolian medicine and medicinal materials.

Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia.

OBJECTIVE: The metabolic reprogramming of acute myeloid leukemia (AML) cells is a compensatory adaptation to meet energy requirements for rapid proliferation. This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells. METHODS: SKM-1 cells (an AML cell line) were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES, a glutaminase inhibitor) or cytarabine. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell apoptosis and reactive oxygen species (ROS) by flow cytometry. Western blotting was conducted to examine the levels of apoptotic proteins, including cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP). Moreover, the human long noncoding RNA (lncRNA) microarray was used to analyze gene expression after glutamine deprivation, and results were confirmed with quantitative RT-PCR (qRT-PCR). The expression of metallothionein 2A (MT2A) was suppressed using siRNA. Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry, respectively, in cells with MT2A knockdown. RESULTS: Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells. The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation. MT2A knockdown increased apoptosis, while proliferation was not affected in SKM-1 cells. In addition, metformin inhibited cell growth and induced apoptosis in SKM-1 cells. Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine. Furthermore, the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells. CONCLUSION: Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

How Can Anomalous-Diffusion Neural Networks Under Connectomics Generate Optimized Spatiotemporal Dynamics.

Spatiotemporal dynamics in the brain have been recognized as strongly related to the formation of perceived and cognitive diseases, such as delusions and hallucinations in Alzheimer's disease. However, two practical considerations are rarely mentioned in related mechanism research: the connectomics networking and the anomalous diffusion generated by the complex medium between neurons and the complex topology of neural networks, respectively. Furthermore, how to optimize the corresponding dynamics behaviors has excellent implications for treating brain diseases. This article first realizes the networking under connectomics for an anomalous-diffusion single-neuron model and applies a nonlinear state feedback control to generate optimized dynamic behaviors, which provides a paradigm of nonequilibrium self-organization driven by anomalous diffusion. Then, by tracing the root distribution of the characteristic equation, some controlled conditions causing or inhibiting Turing instability and Hopf bifurcation are deduced, and the effects of self-diffusion and cross diffusion on Turing instability range are also revealed. At last, thorough numerical simulations are updated to illustrate the results. It is emphasized that delay, self-diffusion, cross diffusion, and fractional order occupy dominant positions in determining the network's spatiotemporal dynamics, and utilizing the control strategy can efficiently reduce Turing instability and delay Hopf bifurcation.

Evaluation of bioequivalence and pharmacokinetic profiles for topical desonide cream using Chinese skin.

INTRODUCTION: Skin blanching assay has been established as a surrogate method for assessing bioequivalence of topical corticosteroids. This study aimed to apply the skin blanching assay to evaluate the bioequivalence of a test desonide cream (T) compared with the reference Desonide® (R) using Chinese skins. Additionally, the pharmacokinetics and safety profiles were also assessed. METHODS: By detecting the degree of skin blanching under different dose duration in a pilot dose-duration-response study, the area under the observed effect-time curve (AUEC) and half of the maximum effect (ED50) was calculated. Based on this, the skin color of different time points after a dose duration of ED50, D1 (0.5×ED50) and D2 (2×ED50) were detected as a pharmacodynamic indicator to compare between test and reference creams. A single-center, single-dose, randomized, open-label, two-cycle crossover pharmacokinetic studies were designed to make sure the exposure of tested formulations was not higher than that of the reference formulations. Subjects experiencing adverse events (AEs) were monitored and utilized for safety analysis. RESULTS: These studies involved twelve subjects for the dose-duration-response study, 100 subjects for the bioequivalence study, and twelve subjects for pharmacokinetic study. The results showed that the population ED50 was 0.88±0.45 h, the mean ratio of area under effective curve (AUEC0-24h) of test and reference preparations was 0.95, with a 90% confidence interval as 88.09%-101.72%, indicating the bioequivalence of the test formulation and Desonide®. The maximum concentration (Cmax) and exposure (AUC0-t) of T and R were 20.8 ± 11.5 pg/mL versus 19.7 ± 10.1 pg/mL, respectively, and 451.04 ± 363.65 pg∙h/mL versus 541.47 ± 581.41 pg∙h/mL, respectively. The systemic exposure of a single dose of the test cream was not higher than that of the reference preparation. All of the volunteers experienced grade 1 adverse events (AEs), suggesting that single administration of the test desonide cream is well tolerated in the Chinese healthy population. CONCLUSIONS: This study demonstrated the applicability of skin blanching assay in Chinese skins and established the bioequivalence of test and reference desonide creams.

Thermoplastic Polyurethane Derived from CO2 for the Cathode Binder in Li-CO2 Battery.

High-energy-density Li-CO2 batteries are promising candidates for large-capacity energy storage systems. However, the development of Li-CO2 batteries has been hindered by low cycle life and high overpotential. In this study, we propose a CO2-based thermoplastic polyurethane (CO2-based TPU) with CO2 adsorption properties and excellent self-healing performance to replace traditional polyvinylidene fluoride (PVDF) as the cathode binder. The CO2-based TPU enhances the interfacial concentration of CO2 at the cathode/electrolyte interfaces, effectively increasing the discharge voltage and lowering the charge voltage of Li-CO2 batteries. Moreover, the CO2 fixed by urethane groups (-NH-COO-) in the CO2-based TPU are difficult to shuttle to and corrode the Li anode, minimizing CO2 side reactions with lithium metal and improving the cycling performance of Li-CO2 batteries. In this work, Li-CO2 batteries with CO2-based TPU as the multifunctional binders exhibit stable cycling performance for 52 cycles at a current density of 0.2 A g-1, with a distinctly lower polarization voltage than PVDF bound Li-CO2 batteries.

An ultrastable 1397-nm laser stabilized by a crystalline-coated room-temperature cavity.

State-of-the-art optical cavities are pivotal in pushing the envelope of laser frequency stability below 10-16. This is often achieved by extending the cavity length or cooling the system to cryogenic temperatures to reduce the thermal noise floor. In our study, we present a 30-cm-long cavity that operates at room temperature and is outfitted with crystalline coatings. The system has a predicted ultralow thermal noise floor of 4.4 × 10-17, comparable to what is observed in cryogenic silicon cavities. A 1397-nm laser is stabilized in this advanced cavity, and the stable frequency is then transferred to the clock transition in strontium optical lattice clocks via a frequency-doubling process. We have meticulously minimized and assessed the technical noise contributions through comparisons with an ultrastable reference laser that is locked to a commercially available 30-cm cavity. The frequency instability of the system is rigorously evaluated using a three-cornered-hat method. The results demonstrate that the laser frequency instability remains below 2 × 10-16 for averaging times ranging from 1 to 50 s. These findings underscore the significant potential of room-temperature cavities with crystalline coatings in high-precision metrology and pave the way for further improvements in optical lattice clocks.

Clinical efficacy and safety of secukinumab in the treatment of generalized pustular psoriasis in the pediatric population: a systematic review of the literature.

Background: Generalized pustular psoriasis (GPP) is a severe type of psoriasis. The current treatment primarily relies on corticosteroids and immunosuppressants. In recent years, biologics have been increasingly utilized in the treatment of this disease, and have demonstrated good clinical efficacy. However, children and adolescents are primarily treated with immunosuppressants, which have limited clinical application due to the serious side effects they may cause. At the same time, the effectiveness of current treatments is unsatisfactory. Secukinumab has been widely reported to be effective and safe in treating this disease. However, there are still insufficient data on its use in treating GPP in children. Objective: To conduct a systematic review of the existing literature on the use of secukinumab for treating generalized pustular psoriasis in children and adolescents, and to evaluate its clinical effectiveness and safety. Methods: We conducted a systematic review of all the literature reporting on the treatment of GPP in children and adolescents with secukinumab. Results: A total of 7 papers (46 patients) were included in this study. After 12 weeks of treatment, all 46 participants were able to achieve a GPPASI score of 90 or higher, with approximately 96% of patients achieving complete clearing of the lesions (GPPASI 100 or JDA0). Adverse events were reported in 8 patients, the rate of adverse reactions was approximately 17%. Conclusion: The treatment of GPP in children and adolescents with secukinumab has a rapid onset of action and a high safety profile. However, the results of the literature may be influenced by publication bias.

Design and Fabrication of Continuous Surface Optical Field Modulator for Angular Spectrum Discreteness Compensation.

The light homogenizing element is a crucial component of the illumination system of the lithography machine. Its primary purpose is to realize the uniform distribution of energy. However, it suffers from a common issue, which is angular spectrum discreteness, which significantly impacts light uniformity. To address this, we design and fabricate random micro-cylindrical lens arrays to obtain a small-angle Gaussian optical field, which can compensate for the angular spectrum discreteness. By adjusting the pitches and curvature radii of the micro-cylindrical lenses separately, we are able to manipulate the divergence angle of the emitted sub-beams, enabling precise angular spectrum modulation. By using mask-moving technology, the angular spectrum modulator is fabricated to generate a Gaussian illumination field. The surface profile is measured and determined with a structural roughness below 10 nm. Furthermore, optical test experiments on the modulator have been conducted, achieving an angle error of less than 0.02° and a balance better than 0.5%.

First Report of Colletotrichum queenslandicum Causing Leaf Anthracnose on Jatropha curcas L in China.

Jatropha curcas L. (Euphorbiaceae), is a valuable multi-purpose crop, previously used for disease treatment and environmental restoration, recently is attention to use jatropha oil for produce biodiese. In June 2023, the leaf disease of approximately 60% of J. curcas was observed in Mazhang, Zhanjiang, Guangdong Province (E110°27'26.8'' N22°6'14.7''). Diseased leaves showed typical anthracnose symptoms of chlorotic regions with brownish sunken necrotic lesions (Figure 1). Sections from the junction of disease were surface disinfected in 75% ethanol and 3% hydrogen peroxide solution for 1 minute each. Four small pieces of infected tissue were removed from the lesion and placed on potato dextrose agar (PDA), and incubated at 25 to 28℃ in the dark. Hyphal tips from the inoculated tissues were subcultured on PDA and two isolates were purified by single spore method. The colonies on PDA were 7.8 cm diam after 10 d at 25 to 28 ℃, covered with dense, cottony, grayish-white aerial mycelium and small dark-based acervuli with orange ooze and dark brown straight setae. Conidia were hyaline, smooth-walled, aseptate, the apex and base rounded, slightly constricted near centre, 12.9 - 13.8 × 3.9 - 4.6 um (av.13.6 × 4.3 µm, n = 50). Appressoria were variable in shape, mostly simple, subglobose or irregular lobes, 5.8-9.6 × 5.7-11.2 um (Figure 2). Perithecia were not observed. These characteristics were consistent with Colletotrichum sp. (Weir, B. S., et al. 2012). Sequences of isolates ACCC 35630 and ACCC 35631 stored in Agricultural Culture Collection of China including internal transcribed spacer (ITS), actin (ACT), beta-tubulin (tub2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and chitin synthase (chs). were amplified (Weir et al, 2012), sequenced and submitted to GenBank (ITS: PP474979 and PP474984; ACT: PP505487 and PP505488; TUB: PP505493 and PP505494; GAPDH: PP505491 and PP505492; CHS: PP505489 and PP505490). The amplicon sizes of ITS, ACT, TUB, GAPDH, and CHS were 550, 652, 500, 264, and 301 bp, respectively. Phylogenetic analyses showed that Isolates 35630 & 35631 were clustered closely association with RHCOL1 and RHCOL3. Phylogenetic analysis with MEGA 7 using the combined ITS-ACT-CHS-GAPDH-TUB2 sequences showed that the two isolates clustered with C. queenslandicum (Figure 3). To test the pathogenicity, ten healthy leaves on plants in the field were wiped with 75% alcohol and sterile water, punctured with a sterile needle and inoculated by adding 10 uL of spore suspension (1 × 105 conidia/ml) to the wounded sites. And two other leaves were added sterile water as controls. Symptoms of anthracnose were observed on leaves similar to the disease described above after 7 days of inoculation, whereas the leaves from the controls remained asymptomatic. C. queenslandicum was reisolated from the inoculated leaves. C. queenslandicum has been reported as a pathogen causing leaf and fruit anthracnose on papaya, coffee, rambutan, avocado and Persian lime etc. in tropical and temperate regions (Kunta, M., et al. 2018), and this is the first report on J. curcas in China as well as worldwide. This disease may have a significant negative impact on J. curcas cultivation.

Melatonin alleviates hyperoxia-induced lung injury through elevating MSC exosomal miR-18a-5p expression to repress PUM2 signaling.

Mesenchymal stem cells (MSC)-derived exosomes (Exo) are a possible option for hyperoxia-induced lung injury (HLI). We wanted to see if melatonin (MT)-pretreated MSC-derived exosomes (MT-Exo) were more effective against HLI, and we also tried to figure out the underlying mechanism. HLI models were established by hyperoxia exposure. HE staining was adopted to analyze lung pathological changes. MTT and flow cytometry were used to determine cell viability and apoptosis, respectively. The mitochondrial membrane potential (MMP) was analyzed using the JC-1 probe. LDH, ROS, SOD, and GSH-Px levels were examined by the corresponding kits. The interactions between miR-18a-5p, PUM2, and DUB3 were analyzed by molecular interaction experiments. MT-Exo could effectively inhibit hyperoxia-induced oxidative stress, inflammatory injury, and apoptosis in lung epithelial cells, while these effects of MT-Exo were weakened by miR-18a-5p knockdown in MSCs. miR-18a-5p reduced PUM2 expression in MLE-12 cells by directly targeting PUM2. In addition, PUM2 inactivated the Nrf2/HO-1 signaling pathway by promoting DUB3 mRNA decay post-transcriptionally. As expected, PUM2 overexpression or DUB3 knockdown abolished the protective effect of MT-Exo on hyperoxia-induced lung epithelial cell injury. MT-Exo carrying miR-18a-5p reduced hyperoxia-mediated lung injury in mice through activating Nrf2/HO-1 pathway. MT reduced PUM2 expression and subsequently activated the DUB3/Nrf2/HO-1 signal axis by increasing miR-18a-5p expression in MSC-derived exosomes to alleviate HLI.