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Background: The objective of this research was to investigate how the combination of semen coicis extract and PD-1 inhibitors can potentially work together to enhance the anti-tumor effects, with a focus on understanding the underlying mechanism. Methods: We obtained the active components and specific targets of semen coicis in the treatment of NSCLC from various databases, namely TCMSP, GeneCard, and OMIM. By utilizing the STRING database and Cytoscape software, we established a protein interaction network (PPI) for the active ingredient of semen coicis and the target genes related to NSCLC. To explore the potential pathways involved, we conducted gene ontology (GO) and biological pathway (KEGG) enrichment analyses, which were further supported by molecular docking technology. Additionally, we conducted cyto-inhibition experiments to verify the inhibitory effects of semen coicis alone or in combination with a PD-1 inhibitor on A549 cells, along with examining the associated pathways. Furthermore, we investigated the synergistic mechanism of these two drugs through cytokine release experiments and the PD-L1 expression study on A549 cells. Results: Semen coicis contains two main active components, Omaine and (S)-4-Nonanolide. Its primary targets include PIK3R1, PIK3CD, PIK3CA, AKT2, and mTOR. Molecular docking experiments confirmed that these ingredients and targets form stable bonds. In vitro experiments showed that semen coicis demonstrates inhibitory effects against A549 cells, and this effect was further enhanced when combined with PD-1 inhibitors. PCR and WB analysis confirmed that the inhibition of the PI3K-AKT-mTOR pathway may contribute to this effect. Additionally, semen coicis was observed to decrease the levels of IFN-γ, IL-6, and TNF-α, promoting the recovery of the human anti-tumor immune response. And semen coicis could inhibit the induced expression of PD‑L1 of A549 cells stimulated by IFN‑γ as well. Conclusion: Semen coicis not only has the ability to kill tumor cells directly but also alleviates the immunosuppression found in the tumor microenvironment. Additionally, it collaboratively enhances the effectiveness of PD-1 inhibitors against tumors by blocking the activation of PI3K-AKT-mTOR. [ABSTRACT FROM AUTHOR]

Summary: There is an urgent need for an oral, efficient and safe regimen for high‐risk APL under the pandemic of COVID‐19. We retrospectively analysed 60 high‐risk APL patients. For induction therapy (IT), in addition to all‐trans retinoic acid (ATRA) and oral arsenic (RIF), 22 patients received oral etoposide (VP16) as cytotoxic chemotherapy (CC), and 38 patients received intravenous CC as historical control group. The median dose of oral VP16 was 1000 mg [interquartile rage (IQR), 650–1250]. One patient died during IT in the control group, 59 evaluable patients (100%) achieved complete haematological remission (CHR) after IT and complete molecular remission (CMR) after consolidation therapy. The median time to CHR and CMR was 36 days (33.8–44) versus 35 days (32–42; p = 0.75) and 3 months (0.8–3.5) versus 3.3 months (2.4–3.7; p = 0.58) in the oral VP16 group and in the control group. Two (9.1%) and 3 (7.9%) patients experienced molecular relapse in different group respectively. The 2‐year estimated overall survival and event‐free survival were 100% versus 94.7% (p = 0.37) and 90.9% versus 89.5% (p = 0.97) respectively. A completely oral, efficient and safe induction regimen including oral VP16 as cytoreductive chemotherapy combined with ATRA and RIF is more convenient to administer for patients with high‐risk APL. [ABSTRACT FROM AUTHOR]

Dihydroorotase (DHOase) is the third enzyme in the six enzymatic reaction steps of the endogenous pyrimidine nucleotide de novo biosynthesis pathway, which is a metabolic pathway conserved in both bacteria and eukaryotes. However, research on the biological function of DHOase in plant pathogenic fungi is very limited. In this study, we identified and named MoPyr4, a homologous protein of Saccharomyces cerevisiae DHOase Ura4, in the rice blast fungus Magnaporthe oryzae and investigated its ability to regulate fungal growth, pathogenicity, and autophagy. Deletion of MoPYR4 led to defects in growth, conidiation, appressorium formation, the transfer and degradation of glycogen and lipid droplets, appressorium turgor accumulation, and invasive hypha expansion in M. oryzae, which eventually resulted in weakened fungal pathogenicity. Long-term replenishment of exogenous uridine-5'-phosphate (UMP) can effectively restore the phenotype and virulence of the ΔMopyr4 mutant. Further study revealed that MoPyr4 also participated in the regulation of the Pmk1-MAPK signaling pathway, co-localized with peroxisomes for the oxidative stress response, and was involved in the regulation of the Osm1-MAPK signaling pathway in response to hyperosmotic stress. In addition, MoPyr4 interacted with MoAtg5, the core protein involved in autophagy, and positively regulated autophagic degradation. Taken together, our results suggested that MoPyr4 for UMP biosynthesis was crucial for the development and pathogenicity of M. oryzae. We also revealed that MoPyr4 played an essential role in the external stress response and pathogenic mechanism through participation in the Pmk1-MAPK signaling pathway, peroxisome-related oxidative stress response mechanism, the Osm1-MAPK signaling pathway and the autophagy pathway. [ABSTRACT FROM AUTHOR]

Coordination polymers (CPs) with a d10-configuration containing metal cations offer interesting photoluminescent properties and hence can be employed as sensors to detect various classes of analytes. Moreover, due to their tuneable pore size they can be employed as adsorbents for various species. Herein, a new d10-configuration Cd(II)-based CP with composition {[Cd(bip)4(H2O)2]n·2NO3} (1) (bip = 3,5-bis(1-imidazol)pyridine) has been synthesized and characterized. Single-crystal X-ray analysis reveals that the Cd(II) center adopts octahedral geometry that is satisfied by four N atoms from the four bip linkers and two aqua ligands, and the resultant CP displays sql topology with the point symbol of (44·62). The CP offers prospective application as a photoluminescent sensor for dichromate anions with a limit of detection of 1.28 ppm and a Stern–Volmer constant (KSV) of 1.51 × 105. Furthermore, CP 1 was employed as an efficient adsorbent for dichromate ions, reaching an equilibrium adsorption capacity of 389.82 mg g−1 within 80 min. The effects of temperature, pH and concentration of dichromate were further investigated, which revealed that CP 1 displays the best adsorption at 30 °C and pH 4 with a dichromate concentration of 200 mg L−1. The possible adsorption mechanism has been proposed with the aid of Hirshfeld surface analysis. [ABSTRACT FROM AUTHOR]

Introduction: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. Methods: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. Results: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p <0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p <0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p <0.05). Conclusion: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD. [ABSTRACT FROM AUTHOR]

Electrochemical CO2 transformation to fuels and chemicals is an effective strategy for conversion of renewable electric energy into storable chemical energy in combination with reducing green-house gas emission. Metal–nitrogen–carbon (M–N–C) single atom catalysts (SAC) have shown great potential in the electrochemical CO2 reduction reaction (CO2RR). However, exploring advanced SACs with simultaneously high catalytic activity and high product selectivity remains a great challenge. In this study, density functional theory (DFT) calculations are combined with machine learning (ML) for rapid and high-throughput screening of high performance CO reduction catalysts. Firstly, the electrochemical properties of 99 M–N–C SACs were calculated by DFT and used as a database. By using different machine learning models with simple features, the investigated SACs were expanded from 99 to 297. Through several effective indicators of catalyst stability, inhibition of the hydrogen evolution reaction, and CO adsorption strength, 33 SACs were finally selected. The catalytic activity and selectivity of the remaining 33 SACs were explored by micro-kinetic simulation based on Marcus theory. Among all the studied SACs, Mn–NC2, Pt–NC2, and Au–NC2 deliver the best catalytic performance and can be used as potential catalysts for CO2/CO conversion to hydrocarbons with high energy density. This effective screening method using a machine learning algorithm can promote the exploration of CO2RR catalysts and significantly reduce the simulation cost. [ABSTRACT FROM AUTHOR]

Objectives: To assess and compare the effectiveness of various treatment approaches for laryngeal contact granulomas (LCG). Methods: A retrospective analysis was conducted on a cohort of 45 patients diagnosed with LCG at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2017 to May 2023. Based on the treatment modalities administered, patients were categorized into three groups: acid suppression alone, hormone injection combined with acid suppression, and surgery combined with acid suppression. Subsequently, the study compared differences in treatment efficacy and average healing time among these three groups, using various indicators. Results: The findings indicate that the granuloma size in LCG patients with hoarseness (0.126, 95% CI 0.087–0.288) was significantly greater compared to LCG patients without hoarseness (0.047, 95% CI 0.014–0.083) (P = 0.001). However, there were no significant variations in age, morphology (unlobulated/lobulated), laterality ratio (left/right), sex ratio (male/female), history of tracheal intubation (non-intubation/intubation), and RFS score (RFS > 7/RFS ≤ 7) (P > 0.05), regardless of the presence of hoarseness symptoms. At the treatment observation endpoint of 3 months, the curative ratio in the group receiving hormone injection combined with acid suppression was found to be significantly higher compared to the group receiving acid suppression alone (P = 0.018). In addition, the average healing time of patients in the hormone injection combined with acid suppression group was notably shorter than that of the acid suppression alone group (P = 0.007). Conclusions: The combination of hormonal injections and acid suppression may enhance the curative ratio and expedite the healing time of LCG. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Objective To analyze the transmission of HIV-1 infections newly found in Luzhou city, Sichuan Province in 2021, and to investigate the risk factors and characteristics of HIV-1 transmission network, so as to provide data for the prevention and control of AIDS epidemic in Luzhou. Methods The blood samples and demographic information of 363 newly reported HIV-1 infections in Luzhou in 2021 were collected. The HIV-1 pol gene sequence was amplified by nested PCR, and the virus subtype and transmissible drug resistance were analyzed according to the pol gene sequence. The molecular network was constructed based on the optimal gene distance (d=1.5%) and the characteristics of molecular transmission network and its influencing factors were analyzed. Results A total of 346 valid sequences were obtained, including 113 cases of CRF07_BC subtype (32.66%), 107 cases of CRF01_AE subtype (30.92%), 99 cases of CRF08_BC subtype (28.61%), 18 cases of CRF105_0108 subtype (5.20%), and 9 cases of other subtypes (2.60%). The rate of transmitted drug resistance of HIV-1 was 15.03% (52/346), and dual drug resistance was detected in 4 samples. A total of 34 molecular clusters were formed, and the number of cases in the clusters ranged from 2 to 25, with 148 individuals (42.77%) included in the transmission network under the optimal genetic distance threshold (1.5%). There were significant differences in age, education level, infection route, genotype, and registered residence registration (P<0.05). Logistic regression found that education level and registered residence were the influencing factors of network access. Conclusion The newly reported HIV -1 infection in Luzhou city shows diversity of virus genes. CRF01_AE, CRF07_BC, and CRF08_ BC subtype have become the main subtype of epidemic virus strains, and molecular transmission network should be established for long-term monitoring in this region to take targeted measures to block its further transmission. [ABSTRACT FROM AUTHOR]

Objective: To assess the extent of recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) damage in patients with idiopathic vocal cord paralysis (IVCP) exhibiting different paralytic sides. Methods: A total of 84 IVCP cases were evaluated using stroboscopic laryngoscopy, voice analysis, and laryngeal electromyography (LEMG). The results were compared between patients with left‐sided paralysis and right‐sided paralysis based on different disease courses (less than or more than 3 months). Results: Initially, the average age and disease progression of IVCP patients were found to be similar regardless of the side of paralysis (p >.05). Additionally, there were no significant variations in voice indicators, such as MPT, DSI, and VHI, between IVCP patients with left and right vocal cord paralysis (p >.05). Furthermore, no disparities were detected in the latencies and amplitudes of the paralyzed RLN and SLN, as well as the durations and amplitudes of the action potentials in the paralyzed TM and PCM, among IVCP patients with left and right vocal cord paralysis (p >.05). Notably, the amplitudes of the left paralytic CM were significantly lower than those of the right paralytic CM (0.45 vs. 0.53, Z = −2.013, p =.044). In addition, no disparities were observed in APDs and amplitudes between the ipsilateral PCM and TM, either for patients with left or right vocal fold paralysis (p >.05). Finally, all the IVCP patients were subdivided into two subgroups according to different disease course (less than or more than 3 months), and in each subgroup, the comparison of voice indicators and LEMG results in IVCP patients with left or right vocal fold paralysis were similar with the above findings (p >.05). Conclusion: Overall, the degree of RLN and SLN damage appeared to be similar in IVCP patients with left and right vocal cord paralysis, provided that the disease course was comparable. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Rice blast is a serious threat to the safe production of grain crops such as rice and wheat. Sporulation, appressorium formation, and invasive growth of Magnaporthe oryzae are the key stages of the development and spread of rice blast epidemics. M. oryzae is a hemibiotrophic fungus that undergoes changes in available carbon sources during the infection cycle. Lipid is a major storage for M. oryzae spores and a major carbon source used in glycerol synthesis and turgor pressure generation in appressoria. The formation of a dense cell wall melanin layer is necessary for an appressorium to produce turgor and to be pathogenic. The plant cell wall is an important carbon source during the infection stage of M. oryzae. Transcription factors regulate gene expression in fungi and are key intermediates between the reception of external environmental signals and the control of development and pathogenicity in M. oryzae. The disease cycle of M. oryzae is controlled by some key transcription factors, such as sporulation by Cos1 and Hox2, appressorium formation by Sfl1, Hox7, and Vrf1, invasive growth by Mst12 and Mig1, and resistance to host basal immunity by Ap1 and Atf1. This review focuses on describing the key transcription factors of M. oryzae that regulate sporulation, appressorium formation, invasive growth, lipid metabolism, carbohydrate metabolism, melanin synthesis, oxidative response, and host basal immunity, as well as the working mechanism of the transcription factors. [ABSTRACT FROM AUTHOR]

The cell cycle is pivotal to cellular differentiation in plant pathogenic fungi. Cell wall integrity (CWI) signaling plays an essential role in coping with cell wall stress. Autophagy is a degradation process in which cells decompose their components to recover macromolecules and provide energy under stress conditions. However, the specific association between cell cycle, autophagy and CWI pathway remains unclear in model pathogenic fungi Magnaporthe oryzae. Here, we have identified MoSwe1 as the conserved component of the cell cycle in the rice blast fungus. We have found that MoSwe1 targets MoMps1, a conserved critical MAP kinase of the CWI pathway, through protein phosphorylation that positively regulates CWI signaling. The CWI pathway is abnormal in the ΔMoswe1 mutant with cell cycle arrest. In addition, we provided evidence that MoSwe1 positively regulates autophagy by interacting with MoAtg17 and MoAtg18, the core autophagy proteins. Moreover, the S phase initiation was earlier, the morphology of conidia and appressoria was abnormal, and septum formation and glycogen degradation were impaired in the ΔMoswe1 mutant. Our research defines that MoSWE1 regulation of G1/S transition, CWI pathway, and autophagy supports its specific requirement for appressorium development and virulence in plant pathogenic fungi. 4YLJWdgoLcEF_sT4NWF7zp Video Abstract [ABSTRACT FROM AUTHOR]

Sphingolipids are critically significant in a range of biological processes in animals, plants, and fungi. In mammalian cells, they serve as vital components of the plasma membrane (PM) in maintaining its structure, tension, and fluidity. They also play a key role in a wide variety of biological processes, such as intracellular signal transduction, cell polarization, differentiation, and migration. In plants, sphingolipids are important for cell development and for cell response to environmental stresses. In pathogenic fungi, sphingolipids are crucial for the initiation and the development of infection processes afflicting humans. However, our knowledge on the metabolism and function of the sphingolipid metabolic pathway of pathogenic fungi affecting plants is still very limited. In this review, we discuss recent developments on sphingolipid pathways of plant pathogenic fungi, highlighting their uniqueness and similarity with plants and animals. In addition, we discuss recent advances in the research and development of fungal-targeted inhibitors of the sphingolipid pathway, to gain insights on how we can better control the infection process occurring in plants to prevent or/and to treat fungal infections in crops. [ABSTRACT FROM AUTHOR]

Objective: To analyze the risk factors for recurrence of laryngeal amyloidosis (LA). Methods: The clinical data of patients with LA admitted in the Otolaryngology Head and Neck Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from August 2009 to June 2022 were analyzed retrospectively; then, the risk factors for recurrence and their impacts on the recurrence time were also analyzed. Results: Of the 44 patients with LA, the majority (38 cases, 86.4%) only involved one anatomical region and the others (6 cases, 13.6%) involved two laryngeal regions concurrently. Overall, the glottic region was the most commonly affected area (28 cases, 63.6%), followed by the supraglottic region (16 cases, 36.4%) and subglottic region (6 cases, 13.6%). In addition, all the lesions were categorized as isolated nodule (31.8%), submucosal localized deposition (52.3%), and submucosal diffuse deposition (15.9%) according to their morphologies under electronic laryngoscope. Finally, six patients (13.6%) had recurrence after operation with a median recurrence time of 24.5 months, and subglottic involvement was confirmed to be an independent risk factor for recurrence of LA by univariate and multivariate logistic regression analyses (P < 0.05). Meanwhile, the patients with subglottic involvement presented as submucosal diffuse deposition had a considerable shorter recurrence time (t = 5.759, P = 0.005). Conclusion: The subglottic involvement is an independent risk factor for recurrence of LA. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Recalcitrant rice blast disease is caused by Magnaporthe oryzae, which has a significant negative economic reverberation on crop productivity. In order to induce the disease onto the host, M. oryzae positively generates many types of small secreted proteins, here named as effectors, to manipulate the host cell for the purpose of stimulating pathogenic infection. In M. oryzae, by engaging with specific receptors on the cell surface, effectors activate signaling channels which control an array of cellular activities, such as proliferation, differentiation and apoptosis. The most recent research on effector identification, classification, function, secretion, and control mechanism has been compiled in this review. In addition, the article also discusses directions and challenges for future research into an effector in M. oryzae. [ABSTRACT FROM AUTHOR]

Magnaporthe oryzae is a pathogenic fungus that seriously harms rice production. Phosphatases and carbon metabolism play crucial roles in the growth and development of eukaryotes. However, it remains unclear how serine/threonine phosphatases regulate the catabolism of triglycerides, a major form of stored lipids. In this study, we identified a serine/threonine protein phosphatase regulatory subunit, Smek1, which is required for the growth, conidiation, and virulence of M. oryzae. Deletion of SMEK1 led to defects in the utilization of lipids, arabinose, glycerol, and ethanol. In glucose medium, the expression of genes involved in lipolysis, long‐chain fatty acid degradation, β‐oxidation, and the glyoxylate cycle increased in the Δsmek1 mutant, which is consistent with ΔcreA in which a carbon catabolite repressor CREA was deleted. In lipid medium, the expression of genes involved in long‐chain fatty acid degradation, β‐oxidation, the glyoxylate cycle, and utilization of arabinose, ethanol, or glycerol decreased in the Δsmek1 mutant, which is consistent with Δcrf1 in which a transcription activator CRF1 required for carbon metabolism was deleted. Lipase activity, however, increased in the Δsmek1 mutant in both glucose and lipid media. Moreover, Smek1 directly interacted with CreA and Crf1, and dephosphorylated CreA and Crf1 in vivo. The phosphatase Smek1 is therefore a dual‐function regulator of the lipid and carbohydrate metabolism, and controls fungal development and virulence by coordinating the functions of CreA and Crf1 in carbon catabolite repression (CCR) and derepression (CCDR). [ABSTRACT FROM AUTHOR]

Background: Recently, Sigma nonopioid intracellular receptor 1 (SIGMAR1) variants have been shown harboring C9orf72 pathogenic repeat expansions in some frontotemporal dementia (FTD) cases. However, no SIGMAR1 genotype analysis has been reported in a cohort absent of C9orf72 pathogenic repeat expansions to date. Objective: The present study investigated the contribution of SIGMAR1 independent of C9orf72 gene status to FTD spectrum syndromes. Methods: We directly sequencing the entire coding region and a minimum of 50 bp from each of the flanking introns of SIGMAR1 gene in 82 sporadic FTD patients (female: male = 42 : 40) and 417 controls. For the patient carrying SIGMAR1 variant, a follow-up 3T MR imaging was performed in the study. Results: Gene sequencing of SIGMAR1 revealed a rare 3′UTR nucleotide variation rs192856872 in a male patient with semantic dementia independent of C9orf72 gene status. The MR imaging showed asymmetrical atrophy in the anterior temporal lobes and the degeneration extends caudally into the posterior temporal lobes as the disease progresses. ESEFinder analysis showed new SRSF1 and SRSF1-IgM-BRCA1 binding sites with significant scores, which is predicted to affect normal splicing. Conclusion: We found a novel SIGMAR1 variant independent of C9orf72 gene status associated with semantic dementia phenotype. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy is an evolutionarily conserved biological process among eukaryotes that degrades unwanted materials such as protein aggregates, damaged mitochondria and even viruses to maintain cell survival. Our previous studies have demonstrated that MoVast1 acts as an autophagy regulator regulating autophagy, membrane tension, and sterol homeostasis in rice blast fungus. However, the detailed regulatory relationships between autophagy and VASt domain proteins remain unsolved. Here, we identified another VASt domain-containing protein, MoVast2, and further uncovered the regulatory mechanism of MoVast2 in M. oryzae. MoVast2 interacted with MoVast1 and MoAtg8, and colocalized at the PAS and deletion of MoVAST2 results in inappropriate autophagy progress. Through TOR activity analysis, sterols and sphingolipid content detection, we found high sterol accumulation in the ΔMovast2 mutant, whereas this mutant showed low sphingolipids and low activity of both TORC1 and TORC2. In addition, MoVast2 colocalized with MoVast1. The localization of MoVast2 in the MoVAST1 deletion mutant was normal; however, deletion of MoVAST2 leads to mislocalization of MoVast1. Notably, the wide-target lipidomic analyses revealed significant changes in sterols and sphingolipids, the major PM components, in the ΔMovast2 mutant, which was involved in lipid metabolism and autophagic pathways. These findings confirmed that the functions of MoVast1 were regulated by MoVast2, revealing that MoVast2 combined with MoVast1 maintained lipid homeostasis and autophagy balance by regulating TOR activity in M. oryzae. [ABSTRACT FROM AUTHOR]

Calcineurin, a key regulator of the calcium signaling pathway, is involved in calcium signal transduction and calcium ion homeostasis. Magnaporthe oryzae is a devastating filamentous phytopathogenic fungus in rice, yet little is known about the function of the calcium signaling system. Here, we identified a novel calcineurin regulatory-subunit-binding protein, MoCbp7, which is highly conserved in filamentous fungi and was found to localize in the cytoplasm. Phenotypic analysis of the MoCBP7 gene deletion mutant (ΔMocbp7) showed that MoCbp7 influenced the growth, conidiation, appressorium formation, invasive growth, and virulence of M. oryzae. Some calcium-signaling-related genes, such as YVC1, VCX1, and RCN1, are expressed in a calcineurin/MoCbp7-dependent manner. Furthermore, MoCbp7 synergizes with calcineurin to regulate endoplasmic reticulum homeostasis. Our research indicated that M. oryzae may have evolved a new calcium signaling regulatory network to adapt to its environment compared to the fungal model organism Saccharomyces cerevisiae. [ABSTRACT FROM AUTHOR]

Based on the panel data of China's industrial carbon emissions from 2015 to 2022, the S-SBM model is scientifically used to measure the industrial carbon emission efficiency, and a spatial model is constructed to empirically analyze the spatial effect of industrial digitalization on carbon emission efficiency. From the regional perspective, it is interesting to find that industrial digitization has shown an overall downward trend of the central, western and northeastern regions showing a roughly N-shaped trend of change. From an industry perspective, we also find that industrial digitization has a relatively high overall impact on the carbon emissions performance of the mining industry with significant changes in the performance of electricity and heat and gas and water production and supply industries. Therefore, the experimental results effectively provide the substantive empirical evidence for policy makers on how to best promote the development of industrial digitization and strengthen the effective application of digital technology affecting carbon emission control in China. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the characteristics of laryngopharyngeal reflux (LPR) by using narrow band imaging (NBI) endoscopy. Study Design: A prospective study. Setting: A large‐volume practice with tertiary care providers. Methods: A total of 67 patients with suspected LPR who underwent 24‐hour multichannel intraluminal impedance–pH monitoring were included from June 2020 to March 2022. Manifestations of NBI endoscopy included submucosal clustered brownish microvessels (CBMs), spotted brownish microvessels, and no special microvessels; the latter 2 formed the non‐CBM group. The manifestations of all patients and their changes were observed after 8 weeks of proton pump inhibitor and symptomatic treatment for patients with LPR, and symptomatic treatment for patients without LPR. Results: According to the results of 24‐hour multichannel intraluminal impedance–pH monitoring, the incidence of submucosal CBMs was significantly higher in patients with LPR (30 cases) than in those without LPR (37 cases, P <.001), particularly in the posterior cricoid area (P <.001). Besides Reflux Finding Score, the incidence of signs such as subglottic edema and vocal fold edema was significantly higher in the CBM group than the non‐CBM group (P <.05). Finally, 22 patients with LPR (91.7%) and only 2 patients without LPR (28.6%) underwent a transformation from CBMs to spotted brownish microvessels after continuous medication for 8 weeks in the CBM group (χ2 = 15.916, P <.001), while no significant change was observed in patients with or without LPR in the non‐CBM group (P >.05). Conclusion: Submucosal CBMs in the posterior cricoid area under NBI endoscopy may be a characteristic of LPR. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Mitophagy, as one of the most important cellular processes to ensure quality control of mitochondria, aims at transporting damaged, aging, dysfunctional or excess mitochondria to vacuoles (plants and fungi) or lysosomes (mammals) for degradation and recycling. The normal functioning of mitophagy is critical for cellular homeostasis from yeasts to humans. Although the role of mitophagy has been well studied in mammalian cells and in certain model organisms, especially the budding yeast Saccharomyces cerevisiae, our understanding of its significance in other fungi, particularly in pathogenic filamentous fungi, is still at the preliminary stage. Recent studies have shown that mitophagy plays a vital role in spore production, vegetative growth and virulence of pathogenic fungi, which are very different from its roles in mammal and yeast. In this review, we summarize the functions of mitophagy for mitochondrial quality and quantity control, fungal growth and pathogenesis that have been reported in the field of molecular biology over the past two decades. These findings may help researchers and readers to better understand the multiple functions of mitophagy and provide new perspectives for the study of mitophagy in fungal pathogenesis. Abbreviations: AIM/LIR: Atg8-family interacting motif/LC3-interacting region; BAR: Bin–Amphiphysin–Rvs; BNIP3: BCL2 interacting protein 3; CK2: casein kinase 2; Cvt: cytoplasm-to-vacuole targeting; ER: endoplasmic reticulum; IMM: inner mitochondrial membrane; mETC: mitochondrial electron transport chain; OMM: outer mitochondrial membrane; OPTN: optineurin; PAS: phagophore assembly site; PD: Parkinson disease; PE: phosphatidylethanolamine; PHB2: prohibitin 2; PX: Phox homology; ROS, reactive oxygen species; TM: transmembrane. [ABSTRACT FROM AUTHOR]

The purpose of this preclinical study in a sheep model was to confirm the feasibility and safety of the LuX-Valve transjugular tricuspid valve (TV) replacement apparatus and to optimize the implantation procedure before beginning first-in-man study. The LuX-Valve was implanted in a sheep model (n = 8) via transjugular approach. Six of eight sheep underwent successful implantation procedure on beating heart. The first two sheep died during the prostheses deployment. In the remaining 6 sheep that survived, postoperative echocardiography results showed there was no paravalvular leakage (PVL) and central tricuspid regurgitation in 5 animals, whereas 1 animal had mild PVL. The mean transvalvular gradient was 1.1 ± 0.9 mm Hg at the 4-week follow-up. No right ventricular outflow tract (RVOT) obstruction, device malposition, pericardial effusion, coronary artery compression, or arrhythmias were observed. This technology may be a promising alternative for TR patients who are at high risk for open-heart surgery. Transjugular tricuspid valved-stent implantation. a Transjugular tricuspid valve replacement in a sheep model. b and c Valved stent. d, e, and f Schematic depiction of the implantation procedure. [ABSTRACT FROM AUTHOR]

With the increase in the number of high-dimensional data, the characteristic phenomenon of unbalanced distribution is increasingly presented in various big data applications. At the same time, most of the existing clustering and feature selection algorithms are based on maximizing the clustering accuracy. In addition, the hybrid approach can effectively solve the clustering problem of unbalanced data. Aiming at the shortcomings of the unbalanced data clustering algorithm, a hybrid high-dimensional multi-objective PSO clustering algorithm is proposed based on the cloud model and entropy (HHCE-MOPSO). Furthermore, the feasibility of the hybrid PSO is verified by the simulation of the multi-objective test function. The results not only broaden the new theory and method of clustering algorithm for unbalanced data, but also verify the accuracy and feasibility of the hybrid PSO. Furthermore, the clustering analysis method based on information entropy is a new method. As a result, the research results have both important scientific value and good practical significance. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Helicobacter pylori (HP) eradication therapy on salivary pepsin concentration in laryngopharyngeal reflux (LPR) patients with HP infection. Materials and methods: A total of 477 patients with suspected LPR were enrolled from June 2020 to September 2021. Reflux symptom index, reflux finding score, the positive rates and disintegrations per minute values of HP infection detected by 14C urea breath test and salivary pepsin concentrations analyzed using enzyme-linked immunosorbent assay were compared in LPR patients and non-LPR patients with or without HP infection. HP-positive patients were treated with HP eradication therapy while HP-negative patients with PPI therapy. Results: The scores of nagging cough (0.88 vs. 0.50, P = 0.035), erythema or hyperemia (1.93 vs. 1.78, P = 0.035) and vocal fold edema (1.04 vs. 0.85, P = 0.025) were higher in the LPR (+) Hp (+) subgroup than in LPR (+) Hp (−) subgroup. The concentrations of salivary pepsin in the Hp (+) subgroup were higher than in the Hp (−) subgroup either in LPR patients (75.24 ng/ml vs. 61.39 ng/ml, P = 0.005) or the non-LPR patients (78.42 ng/ml vs. 48.96 ng/ml, P = 0.024). Compared to baseline (before treatment), scores of nagging cough (0.35 vs. 0.84, P = 0.019) and erythema or hyperemia (1.50 vs. 1.83, P = 0.039) and the concentrations of salivary pepsin (44.35 ng/ml vs. 74.15 ng/ml, P = 0.017) in LPR patients with HP infection decreased after HP treatment; yet, this was not observed for the LPR patients without HP infection treated with PPI only (P > 0.05). Conclusion: HP infection may aggravate the symptoms and signs of LPR patients, partly by increasing their salivary pepsin concentration. [ABSTRACT FROM AUTHOR]

Purine nucleotides are indispensable compounds for many organisms and participate in basic vital activities such as heredity, development, and growth. Blocking of purine nucleotide biosynthesis may inhibit proliferation and development and is commonly used in cancer therapy. However, the function of the purine nucleotide biosynthesis pathway in the pathogenic fungus Magnaporthe oryzae is not clear. In this study, we focused on the de novo purine biosynthesis (DNPB) pathway and characterized MoAde8, a phosphoribosylglycinamide formyltransferase, catalyzing the third step of the DNPB pathway in M. oryzae. MoAde8 was knocked out, and the mutant (∆Moade8) exhibited purine auxotroph, defects in aerial hyphal growth, conidiation, and pathogenicity, and was more sensitive to hyperosmotic stress and oxidative stress. Moreover, ∆Moade8 caused decreased activity of MoTor kinase due to blocked purine nucleotide synthesis. The autophagy level was also impaired in ∆Moade8. Additionally, MoAde5, 7, 6, and 12, which are involved in de novo purine nucleotide biosynthesis, were also analyzed, and the mutants showed defects similar to the defects of ∆Moade8. In summary, de novo purine nucleotide biosynthesis is essential for conidiation, development, and pathogenicity in M. oryzae. [ABSTRACT FROM AUTHOR]

Magnaporthe oryzae is an important pathogen that causes a devastating disease in rice. It has been reported that the dual-specificity LAMMER kinase is conserved from yeast to animal species and has a variety of functions. However, the functions of the LAMMER kinase have not been reported in M. oryzae. In this study, we identified the unique LAMMER kinase MoKns1 and analyzed its function in M. oryzae. We found that in a MoKNS1 deletion mutant, growth and conidiation were primarily decreased, and pathogenicity was almost completely lost. Furthermore, our results found that MoKns1 is involved in autophagy. The ΔMokns1 mutant was sensitive to rapamycin, and MoKns1 interacted with the autophagy-related protein MoAtg18. Compared with the wild-type strain 70−15, autophagy was significantly enhanced in the ΔMokns1 mutant. In addition, we also found that MoKns1 regulated DNA damage stress pathways, and the ΔMokns1 mutant was more sensitive to hydroxyurea (HU) and methyl methanesulfonate (MMS) compared to the wild-type strain 70−15. The expression of genes related to DNA damage stress pathways in the ΔMokns1 mutant was significantly different from that in the wild-type strain. Our results demonstrate that MoKns1 is an important pathogenic factor in M. oryzae involved in regulating autophagy and DNA damage response pathways, thus affecting virulence. This research on M. oryzae pathogenesis lays a foundation for the prevention and control of M. oryzae. [ABSTRACT FROM AUTHOR]

Kiwifruit is a kind of nutritious fruit, which is very perishable after harvest. Thus the preservation technology of postharvest kiwifruit is important for the industrial development and prosperity. Therefore, in this paper, the researches on kiwifruit preservation were summarized from three aspects including biological preservation technology, physical preservation technology and chemical preservation technology, and the researches on biological preservation technology of postharvest kiwifruit in recent years were mainly reviewed from two aspects including natural extract preservation technology and microbial preservation technology, finally the development trends of kiwifruit preservation technology in the future were prospected, hoping to provide a theoretical basis for the further development of kiwifruit preservation technologies. [ABSTRACT FROM AUTHOR]

Objective: People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology. Methods: Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities. Results: 290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways. Conclusion: Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities. [ABSTRACT FROM AUTHOR]

Quantum transducers that can convert quantum signals from the microwave to the optical domain are a crucial optical interface for quantum information technology. Coherent microwave-to-optics conversions have been realized with various physical platforms, but all of them are limited to low efficiencies of less than 50%—the threshold of the no-cloning quantum regime. Here we report coherent microwave-to-optics transduction using Rydberg atoms and off-resonant scattering technique with an efficiency of 82 ± 2% and a bandwidth of about 1 MHz. The high conversion efficiency is maintained for microwave photons ranging from thousands to about 50, suggesting that our transduction is readily applicable to the single-photon level. Without requiring cavities or aggressive cooling for the quantum ground states, our results would push atomic transducers closer to practical applications in quantum technologies. The demonstration of high-efficiency coherent microwave-to-optics conversion could push atomic transducers closer to practical applications in quantum technologies. [ABSTRACT FROM AUTHOR]

Wild rice (Oryza granulata) is a natural resource pool containing abundant unknown endophytic fungi species. There are few reports on the endophytic fungi in wild rice. Here, one isolate recovered from wild rice roots was identified as a new species Pseudophialophora oryzae sp. nov based on the molecular phylogeny and morphological characteristics. Fluorescent protein-expressing P. oryzae was used to monitor the fungal colonization pattern. Hyphae invaded the epidermis to the inner cortex but not into the root stele. The inoculation of P. oryzae promoted the rice growth, with the growth parameters of chlorophyll content, shoot height, root length, fresh shoot weight, fresh root weight and dry weight increasing by 24.10, 35.32, 19.35, 90.00, 33.3, and 79.17%, respectively. P. oryzae induced up-regulation of nitrate transporter OsPTR9 and potassium transporter OsHAK16 by 7.28 ± 0.84 and 2.57 ± 0.80 folds, promoting nitrogen and potassium elements absorption. In addition, P. oryzae also conferred a systemic resistance against rice blast, showing a 72.65 and 75.63% control rate in sterile plates and potting conditions. This systemic resistance was mediated by the strongly up-regulated expression of resistance-related genes NAC , OsSAUR2 , OsWRKY71 , EL5 , and PR1 α. Since P. oryzae can promote rice growth, biomass and induce systemic disease resistance, it can be further developed as a new biogenic agent for agricultural production, providing a new approach for biocontrol of rice blast. [ABSTRACT FROM AUTHOR]

Summary: The development and pathogenicity of the fungus Magnaporthe oryzae, the causal agent of destructive rice blast disease, require it to perceive external environmental signals. Opy2, an overproduction‐induced pheromone‐resistant protein 2, is a crucial protein for sensing external signals in Saccharomyces cerevisiae. However, the biological functions of the homologue of Opy2 in M. oryzae are unclear. In this study, we identified that MoOPY2 is involved in fungal development, pathogenicity, and autophagy in M. oryzae. Deletion of MoOPY2 resulted in pleiotropic defects in hyphal growth, conidiation, germ tube extension, appressorium formation, appressorium turgor generation, and invasive growth, therefore leading to attenuated pathogenicity. Furthermore, MoOpy2 participates in the Osm1 MAPK pathway and the Mps1 MAPK pathway by interacting with the adaptor protein Mst50. The interaction sites of Mst50 and MoOpy2 colocalized with the autophagic marker protein MoAtg8 in the preautophagosomal structure sites (PAS). Notably, the ΔMoopy2 mutant caused cumulative MoAtg8 lipidation and rapid GFP‐MoAtg8 degradation in response to nitrogen starvation, showing that MoOpy2 is involved in the negative regulation of autophagy activity. Taken together, our study revealed that MoOpy2 of M. oryzae plays an essential role in the orchestration of fungal development, appressorium penetration, autophagy and pathogenesis. [ABSTRACT FROM AUTHOR]

Summary: Magnaporthe oryzae is an important plant pathogen that causes rice blast. Hse1 and Vps27 are components of ESCRT‐0 involved in the multivesicular body (MVB) sorting pathway and biogenesis. To date, the biological functions of ESCRT‐0 in M. oryzae have not been determined. In this study, we identified and characterized Hse1 and Vps27 in M. oryzae. Disruption of MoHse1 and MoVps27 caused pleiotropic defects in growth, conidiation, sexual development and pathogenicity, thereby resulting in loss of virulence in rice and barley leaves. Disruption of MoHse1 and MoVps27 triggered increased lipidation of MoAtg8 and degradation of GFP‐MoAtg8, indicating that ESCRT‐0 is involved in the regulation of autophagy. ESCRT‐0 was determined to interact with coat protein complex II (COPII), a regulator functioning in homeostasis of the endoplasmic reticulum (ER homeostasis), and disruption of MoHse1 and MoVps27 also blocked activation of the unfolded protein response (UPR) and autophagy of the endoplasmic reticulum (ER‐phagy). Overall, our results indicate that ESCRT‐0 plays critical roles in regulating fungal development, virulence, autophagy and ER‐phagy in M. oryzae. [ABSTRACT FROM AUTHOR]

Asthma patients may increase their susceptibility to SARS-CoV-2 infection and the poor prognosis of coronavirus disease 2019 (COVID-19). However, anti-COVID-19/asthma comorbidity approaches are restricted on condition. Existing evidence indicates that luteolin has antiviral, anti-inflammatory, and immune regulation capabilities. We aimed to evaluate the possibility of luteolin evolving into an ideal drug and explore the underlying molecular mechanisms of luteolin against COVID-19/asthma comorbidity. We used system pharmacology and bioinformatics analysis to assess the physicochemical properties and biological activities of luteolin and further analyze the binding activities, targets, biological functions, and mechanisms of luteolin against COVID-19/asthma comorbidity. We found that luteolin may exert ideal physicochemical properties and bioactivity, and molecular docking analysis confirmed that luteolin performed effective binding activities in COVID-19/asthma comorbidity. Furthermore, a protein–protein interaction network of 538 common targets between drug and disease was constructed and 264 hub targets were obtained. Then, the top 6 hub targets of luteolin against COVID-19/asthma comorbidity were identified, namely, TP53, AKT1, ALB, IL-6, TNF, and VEGFA. Furthermore, the enrichment analysis suggested that luteolin may exert effects on virus defense, regulation of inflammation, cell growth and cell replication, and immune responses, reducing oxidative stress and regulating blood circulation through the Toll-like receptor; MAPK, TNF, AGE/RAGE, EGFR, ErbB, HIF-1, and PI3K–AKT signaling pathways; PD-L1 expression; and PD-1 checkpoint pathway in cancer. The possible "dangerous liaison" between COVID-19 and asthma is still a potential threat to world health. This research is the first to explore whether luteolin could evolve into a drug candidate for COVID-19/asthma comorbidity. This study indicated that luteolin with superior drug likeness and bioactivity has great potential to be used for treating COVID-19/asthma comorbidity, but the predicted results still need to be rigorously verified by experiments. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of interferon-α (IFN-α) as maintenance therapy in patients with favorable-risk acute myeloid leukemia (AML), this retrospective study enrolled 84 patients with favorable-risk AML: 42 patients who received IFN-α maintenance therapy and 42 patients who did not (control). The median follow-up time and duration of IFN-α treatment was 26 (6–54) months and 18 (2–24) months, respectively. The 4-year estimated relapse-free survival (RFS) after the last consolidation chemotherapy was 86.8% (95% confidence interval (CI), 75.8–97.8%) in the IFN-α group and 55.7% (95% CI, 37.2–74.3%) in the control group (p=.007). The 4-year estimated overall survival was 94.4% (95% CI, 86.8–102%) and 76.4% (95% CI, 61.9–90.9%) in IFN-α and control groups, respectively (p=.040). The Cox regression analysis showed that IFN-α treatment was the only independent factor affecting RFS (p=.004). Maintenance therapy with IFN-α may prevent relapse in favorable-risk AML after consolidation chemotherapy. [ABSTRACT FROM AUTHOR]

Summary: Despite the high cure probability for acute promyelocytic leukaemia (APL), a minority of patients will relapse and the risk factors for relapse are unclear. We retrospectively analysed 212 patients who were diagnosed with non‐high‐risk APL and received all‐trans retinoic acid (ATRA) plus arsenic as front‐line therapy at Peking University Institute of Hematology from February 2014 to December 2018. A total of 176 patients (83%) received oral arsenic (realgar‐indigo naturalis formula) plus ATRA, 36 patients (17%) received arsenic trioxide plus ATRA and 203 patients were evaluable for relapse. After a median (range) follow‐up of 53·6 (24·3–85·4) months, two patients had molecular relapse and eight had haematological relapse. A promyelocytic leukaemia/retinoic acid receptor alpha (PML‐RARA) transcript level of ≥6·5% at the end of induction therapy was associated with relapse (P = 0·031). The 5‐year cumulative incidence of relapse, event‐free survival and overall survival were 5·5%, 92·3% and 96·3% respectively. In conclusion, the present long‐term follow‐up study further confirmed the high cure probability of ATRA plus oral arsenic as front‐line therapy for non‐high‐risk APL and showed that the PML‐RARA transcript level at the end of induction therapy was associated with relapse. [ABSTRACT FROM AUTHOR]

Septins, a conserved family of GTP-binding proteins, are widely recognized as an essential cytoskeletal component, playing important roles in a variety of biological processes, including division, polarity, and membrane remodeling, in different eukaryotes. Although the roles played by septins were identified in the model organism Saccharomyces cerevisiae, their importance in other fungi, especially pathogenic fungi, have recently been determined. In this review, we summarize the functions of septins in pathogenic fungi in the cell cycle, autophagy, endocytosis and invasion host-microbe interactions that were reported in the last two years in the field of septin cell biology. These new discoveries may be expanded to investigate the functions of septin proteins in fungal pathogenesis and may be of wide interest to the readers of Microbiology and Molecular Pathology. [ABSTRACT FROM AUTHOR]

Objective: To investigate the protoplast preparation and transformation system of endophytic fungus Falciphora oryzae. Results: F. oryzae strain obtained higher protoplast yield and effective transformation when treated with enzyme digestion solution containing 0.9 M KCl solution and 10 mg mL−1 glucanase at 30 °C with shaking at 80 rpm for 2–3 h. When the protoplasts were plated on a regenerations-agar medium containing 1 M sucrose, the re-growth rate of protoplasts was the highest. We successfully acquired green fluorescent protein-expressing transformants by transforming the pKD6-GFP vector into protoplasts. Further, the GFP expression in fungal hyphae possessed good stability and intensity during symbiosis in rice roots. Conclusions: This study provided a protoplast transformation system of F. oryzae, creating opportunities for future genetic research in other endophytic fungi. [ABSTRACT FROM AUTHOR]

Sterols are a class of lipids critical for fundamental biological processes and membrane dynamics. These molecules are synthesized in the endoplasmic reticulum (ER) and are transported bi-directionally between the ER and plasma membrane (PM). However, the trafficking mechanism of sterols and their relationship with macroautophagy/autophagy are still poorly understood in the rice blast fungus Magnaporthe oryzae. Here, we identified the VAD1 Analog of StAR-related lipid transfer (VASt) domain-containing protein MoVast1 via co-immunoprecipitation in M. oryzae. Loss of MoVAST1 resulted in conidial defects, impaired appressorium development, and reduced pathogenicity. The MoTor (target of rapamycin in M. oryzae) activity is inhibited because MoVast1 deletion leads to high levels of sterol accumulation in the PM. Site-directed mutagenesis showed that the 902 T site is essential for localization and function of MoVast1. Through filipin or Flipper-TR staining, autophagic flux detection, MoAtg8 lipidation, and drug sensitivity assays, we uncovered that MoVast1 acts as a novel autophagy inhibition factor that monitors tension in the PM by regulating the sterol content, which in turn modulates the activity of MoTor. Lipidomics and transcriptomics analyses further confirmed that MoVast1 is an important regulator of lipid metabolism and the autophagy pathway. Our results revealed and characterized a novel sterol transfer protein important for M. oryzae pathogenicity. Abbreviations: AmB: amphotericin B; ATMT: Agrobacterium tumefaciens-mediated transformation; CM: complete medium; dpi: days post-inoculation; ER: endoplasmic reticulum; Flipper-TR: fluorescent lipid tension reporter; GO: Gene ontology; hpi: hours post-inoculation; IH: invasive hyphae; KEGG: kyoto encyclopedia of genes and genomes; MoTor: target of rapamycin in Magnaporthe oryzae; PalmC: palmitoylcarnitine; PM: plasma membrane; SD-N: synthetic defined medium without amino acids and ammonium sulfate; TOR: target of rapamycin; VASt: VAD1 Analog of StAR-related lipid transfer; YFP, yellow fluorescent protein. [ABSTRACT FROM AUTHOR]

Individual variations in metabolic rate, locomotion capacity and hypoxia tolerance and their relationships were investigated in three cyprinid species [crucian carp (Carassius auratus), common carp (Cyprinus carpio) and qingbo (Spinibarbus sinensis), in 60 individuals of each species]. Either the active metabolic rate (AMR) and critical swimming speed (Ucrit) (30 individuals) or critical oxygen tension (Pcrit) and loss of equilibrium (LOE) (30 individuals) were measured in each species after measuring the resting metabolic rate (RMR). Both the AMR and Ucrit were found to be significantly and positively correlated with the RMR in all three cyprinid species, indicating that high-RMR individuals have high aerobic capacity and thus good swimming performance. Pcrit was positively correlated with the RMR in all three species, whereas the LOE was highly positively correlated, weakly positively correlated and not correlated with the RMR in qingbo, common carp and crucian carp, respectively, possibly due to specialized morphological and biochemical adaptations involved in hypoxia tolerance in crucian and common carp. Crucian carp showed relatively poor swimming performance, i.e., a low Ucrit (relatively high variation), strong hypoxia tolerance, and low LOE (relatively low variation); qingbo showed relatively good swimming performance (relatively low variation) and weak hypoxia tolerance (relatively high variation); and common carp showed moderate swimming performance and relatively strong hypoxia tolerance (moderate variation). These interspecific differences may be due to the different lifestyles of these cyprinid fishes based on their associated fast–slow-flow regime and are outcomes of long-term selection. [ABSTRACT FROM AUTHOR]

Controversial results have been reported about the association of calcium, magnesium, and phosphorus and stroke risk, but none in China. To investigate the association between dietary calcium, magnesium, phosphorus, and stroke incidence in Chinese adults, we collected data from the China Health and Nutrition Survey (CHNS) from 2004 to 2011, including 6411 participants aged 45–79 years and free of stroke at baseline. Diet was assessed by interviews combining 3-d 24-h food recalls and household food inventory weighing at each survey round. The stroke incident was identified based on the validated self-report. Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For 32,024 person-years of follow-up, 179 stroke cases were documented. After adjustment for major lifestyle and dietary risk factors, calcium intake was positively associated with reduced stroke risk, and the HR of stroke comparing extreme quartiles was 0.53 (95% CI 0.29–0.96, Ptrend = 0.03). In further stratified analyses, significant heterogeneity across sex strata was found (Pinteraction = 0.03). Dietary calcium intake among men was more inversely related to stroke, with HRs being 0.33 (95% CI 0.15–0.76, Ptrend = 0.02), compared to 1.24 (95% CI 0.46–3.35, Ptrend = 0.89) among women. However, no significant association between stroke and magnesium or phosphorus was revealed. Our findings suggest that higher dietary calcium intake was associated with a lower risk of stroke in Chinese adults, particularly in men. [ABSTRACT FROM AUTHOR]

Objectives: To compare the ability of Frailty Phenotype (FP), FRAIL and Frailty Index (FI) to predict adverse outcomes. Design: A prospective cohort study. Setting: A senior community in Beijing, China. Participants: A total of 188 older adults aged 65 years or older (mean age 84.0 ± 4.4 years, 58.5% female). Measurements: Frailty was evaluated by FP, FRAIL and FI. The agreement between scales was assessed by Cohen kappa coefficient. The predictive value of the three scales for adverse outcomes during one-year follow-up period were analyzed using decision curve analysis(DCA) and receiver operating characteristic curve (ROC) analysis. Results: Frailty ranged from 25% (FRAIL) to 42.6% (FI). The agreement between scales was moderate to good (Cohen's kappa coefficient 0.44∼0.61). DCA showed though the curves of the scales overlapped across all relevant risk thresholds, clinical treating had a higher net benefit than "treat all" and "treat none" when risk of unplanned hospital visits ≥30%, risk of functional decline or falls ≥15%. The three scales had similar predictive value for unplanned hospital visits (area under ROC, AUC 0.63, 0.64 and 0.69). FRAIL and FI had similar predictive value for functional decline (AUC 0.63,0.65). FI had predictive value for falls (AUC 0.65). Conclusions: All three scales showed clinical utility but FRAIL may be best in practice because it is simple. Multidimensional measures of frailty are better than unidimensional for prediction of adverse outcomes among older adults. [ABSTRACT FROM AUTHOR]

TQ‐B3203 is a new topoisomerase I inhibitor derived from camptothecin. In this paper, a simple and reliable ultra high‐performance liquid chromatography‐tandem mass spectrometric method was developed and validated for determination of TQ‐B3203 in human plasma with TQ‐B3203‐d8 used as the internal standard. Bis(p‐nitrophenyl)phosphate (2 mol/L) was added to ensure the stability of TQ‐B3203 in human plasma. Plasma samples were protein precipitated by methanol and processed samples were chromatographed on an AQUITY BEH C8 column (50 × 2.1 mm, id 1.7 μm) with acetonitrile and water (0.1% formic acid) as the mobile phase. The calibration curves showed good linearity (R≥0.99) over the concentration range of 0.5–500 ng/mL. Within‐ and between‐run precision were ≤5.8% and the accuracy was within the range of −8.3 to 14.0%. This method was further successfully applied to a pharmacokinetic study of TQ‐B3203 in Chinese advanced solid cancer patients after administration of TQ‐B3203 liposome injection. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study investigated the effects of cognitive behavioral therapy (CBT) on depression, anxiety, response rates, and adverse events in patients with locoregional advanced nasopharyngeal carcinoma (NPC). Methods: A total of 269 patients with diagnosis of stage III-IVA NPC received either CBT plus chemoradiotherapy (CBT group, n = 136) or treatment as usual (TAU) plus chemoradiotherapy (TAU group, n = 133). Patients in the CBT group received a series of 6 CBT sessions for 6 weeks during concurrent chemoradiotherapy. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS) score at baseline, the completion of radiotherapy, and 6, 12, and 24 months after radiotherapy. Response rates and adverse events were also evaluated. Results: Patients in the CBT group showed significantly less depression and anxiety than patients in the TAU group after the completion of radiotherapy (P <.05). Complete response rates were 99.3% (135/136) and 92.5% (123/133) in the CBT group and TAU group with a small effect size (Phi coefficient =.171), respectively (P =.005). Compared with the TAU group, the CBT group showed a significantly lower incidence of acute adverse events and late toxic effects. Conclusions: The addition of CBT to chemoradiotherapy significantly reduced depressive and anxiety symptoms. CBT combined with chemoradiotherapy is associated with improved response rates, with reduced incidence of toxic effects in patients with locoregional advanced NPC. Based on this study, we registered a randomized controlled clinical trials to better define the role of CBT in patients with locoregional advanced NPC (Registration number: ChiCTR2000034701). [ABSTRACT FROM AUTHOR]

Pyricularia oryzae is the causal agent of blast disease on staple gramineous crops. Sulphur is an essential element for the biosynthesis of cysteine and methionine in fungi. Here, we targeted the P. oryzae PoMET3 encoding the enzyme ATP sulfurylase, and PoMET14 encoding the APS (adenosine-5′-phosphosulphate) kinase that are involved in sulfate assimilation and sulphur-containing amino acids biosynthesis. In P. oryzae, deletion of PoMET3 or PoMET14 separately results in defects of conidiophore formation, significant impairments in conidiation, methionine and cysteine auxotrophy, limited invasive hypha extension, and remarkably reduced virulence on rice and barley. Furthermore, the defects of the null mutants could be restored by supplementing with exogenous cysteine or methionine. Our study explored the biological functions of sulfur assimilation and sulphur-containing amino acids biosynthesis in P. oryzae. [ABSTRACT FROM AUTHOR]