Miracle-dz/UniFAR-FTUs huggingface dataset:
A cAMP phosphodiesterase is essential for sclerotia formation and virulence in Sclerotinia sclerotiorum

Sclerotinia sclerotiorum is a plant pathogenic fungus that causes white mold or stem rot diseases. It affects mostly dicotyledonous crops, resulting in significant economic losses worldwide. Sclerotia formation is a special feature of S. sclerotiorum, allowing its survival in soil for extended periods and facilitates the spread of the pathogen. However, the detailed molecular mechanisms of how sclerotia are formed and how virulence is achieved in S. sclerotiorum are not fully understood. Here, we report the identification of a mutant that cannot form sclerotia using a forward genetics approach. Next-generation sequencing of the mutant’s whole genome revealed candidate genes. Through knockout experiments, the causal gene was found to encode a cAMP phosphodiesterase (SsPDE2). From mutant phenotypic examinations, we found that SsPDE2 plays essential roles not only in sclerotia formation, but also in the regulation of oxalic acid accumulation, infection cushion functionality and virulence. Downregulation of SsSMK1 transcripts in Sspde2 mutants revealed that these morphological defects are likely caused by cAMP-dependent inhibition of MAPK signaling. Moreover, when we introduced HIGS construct targeting SsPDE2 in Nicotiana benthamiana, largely compromised virulence was observed against S. sclerotiorum. Taken together, SsPDE2 is indispensable for key biological processes of S. sclerotiorum and can potentially serve as a HIGS target to control stem rot in the field.
Prevalence and genotype distribution of HPV infection among women in Xiamen, China

Objective This study aimed to evaluate the prevalence of HPV and genotype distribution among female populations in Xiamen, Fujian Province, China, which can be conducive for local governments to formulate cervical cancer screening and HPV vaccine strategies. Methods Cervical swabs were collected from 47,926 participants aged 16–92 years at the Women and Children’s Hospital, Xiamen University, from November 2019 to June 2020. HPV DNA was extracted and detected using conventional PCR, followed by HPV subtype-specific hybridisation. HPV infection rates based on different groups were compared using the χ2 test. HPV prevalence and the corresponding 95% confidence intervals (95% CI) were calculated using SPSS 19.0. Results The overall HPV prevalence among the 47,926 cervical swabs that were analysed was 15.13%, of which single, double, and multiple infections accounted for 76.83, 16.70 and 6.47%, respectively. The age-specific prevalence of HPV infection presented a “U” curve with a HPV prevalence peak observed in women aged <20 years. The gynaecology clinic group had significantly higher HPV positive rates than the health examination group (p < 0.001). The five most common HR-HPV subtypes in Xiamen were HPV52, 58, 16, 51, and 39 (2.69, 1.63, 1.23, 1.05, and 0.98%, respectively). The five most common LR-HPV subtypes were HPV54, 61, 81, 70, 34, and 84 (0.92, 0.86, 0.71, 0.45 and 0.35%, respectively). Conclusion Our findings demonstrate that the 9-valent HPV vaccine is recommended for regular immunisation in Xiamen. It is necessary for elderly women to participate in HPV screening to decrease the morbidity and mortality of cervical cancer.
Developing a nomogram for predicting surgical intervention in pediatric intussusception after hydrostatic reduction

Purpose The aim of this study was to develop and validate a nomogram for predicting surgical intervention in pediatric intussusception after hydrostatic reduction. Methods Children with intussusception who had treated with sonographically guided saline hydrostatic reduction as an initial treatment were enrolled in this study. The enrolled patients were randomly selected for training and validation sets, and the split ratio was 7:3. The medical records of enrolled patients were retrospectively reviewed. The patients were divided into a surgery and a non-surgery group according to the results of the nonsurgical reduction. A model for predicting the risk of surgical treatment was virtualized by the nomogram using logistic regression analysis. Results The training set consisted of 139 patients and the validation set included 74. After logistic regression analysis using training set, duration of symptoms, bloody stools, white blood cells (WBCs), creatine kinase isoenzyme (CK-MB), long-axis diameter, poor prognostic signs by ultrasound and mental state were identified as the independent predictors of surgical intervention for intussusception. A model that incorporated the above independent predictors was developed and presented as a nomogram. The C-index of the nomogram in the validation set was 0.948 (95% CI, 0.888–1.000). The calibration curve demonstrated a good agreement between prediction and observation. The decision curve analysis (DCA) curve showed that the model achieved a net benefit across all threshold probabilities. Conclusion Based on the predictors of duration of symptoms, bloody stools, WBCs, CK-MB, long-axis diameter, poor prognostic signs by ultrasound and mental state, we developed a nomogram for predicting surgical intervention after hydrostatic reduction. This nomogram could be applied directly to facilitate pre-surgery decision for pediatric intussusception.
Rewiring carbon flow in Synechocystis PCC 6803 for a high rate of CO2-to-ethanol under an atmospheric environment

Cyanobacteria are an excellent microbial photosynthetic platform for sustainable carbon dioxide fixation. One bottleneck to limit its application is that the natural carbon flow pathway almost transfers CO2 to glycogen/biomass other than designed biofuels such as ethanol. Here, we used engineered Synechocystis sp. PCC 6803 to explore CO2-to-ethanol potential under atmospheric environment. First, we investigated the effects of two heterologous genes (pyruvate decarboxylase and alcohol dehydrogenase) on ethanol biosynthesis and optimized their promoter. Furthermore, the main carbon flow of the ethanol pathway was strengthened by blocking glycogen storage and pyruvate-to-phosphoenolpyruvate backflow. To recycle carbon atoms that escaped from the tricarboxylic acid cycle, malate was artificially guided back into pyruvate, which also created NADPH balance and promoted acetaldehyde conversion into ethanol. Impressively, we achieved high-rate ethanol production (248 mg/L/day at early 4 days) by fixing atmospheric CO2. Thus, this study exhibits the proof-of-concept that rewiring carbon flow strategies could provide an efficient cyanobacterial platform for sustainable biofuel production from atmospheric CO2. Graphical Abstract Carbon flux rewiring enables high rate of CO2-to-ethanol in photosynthetic microorganism.
Complex interplays between limpets and alien species in South Africa: multispecies interactions, zonation and size effects

Integrating observations and experiments, we address the progressive effects of three alien species, the mussels Mytilus galloprovincialis and Semimytilus patagonicus, and the barnacle Balanus glandula, on limpet species in South Africa. We describe four aspects: (1) Interactions among algae, the limpet Scutellastra granularis and M. galloprovincialis. (2) The influences of B. glandula on S. granularis and on the periwinkle Afrolittorina knysnaensis. (3) Transformation of the zonation of S. granularis by the successive arrival of these three aliens. (4) Assessment of how effective the published predictors of the effects of M. galloprovincialis have been when applied to S. patagonicus. We conclude: (a) Scutellastra granularis improves mussel survival and condition by regulating algae that would otherwise overgrow and smother the mussels. (b) Balanus glandula has largely occupied the upper half of rocky shores, and at high densities depletes or eliminates suitable bare-rock habitat for S. granularis. However, it has positive effects on another gastropod, A. knysnaensis. (c) Mytilus galloprovincialis dominates the midshore and has positive effects on the recruitment of S. granularis, but negatively influences adults of this limpet, so that its size composition, density, reproductive output and zonation are all altered by this mussel. (d) Semimytilus patagonicus presents different challenges to those created by M. galloprovincialis, settling at much greater densities, lower down the shore, and reaching smaller maximum sizes. Rather than generating a favourable habitat for epizootic S. granularis recruits and juveniles, it almost completely excludes that limpet. We conclude that the influences of alien species are not readily predictable, depending on the nature of the invader and recipient species, environmental conditions and complex interactions among species. Collectively, the three alien species now cover almost all zones on wave-exposed rocky shores, completing the ‘zonation squeeze’ on limpets, but are less influential on wave-sheltered shores and in years when recruitment is low.
High-quality genome assembly of Verticillium dahliae VD991 allows for screening and validation of pathogenic genes

Verticillium dahliae (V. dahliae) is a notorious soil-borne pathogen causing Verticillium wilt in more than 400 dicotyledonous plants, including a wide range of economically important crops, such as cotton, tomato, lettuce, potato, and romaine lettuce, which can result in extensive economic losses. In the last decade, several studies have been conducted on the physiological and molecular mechanisms of plant resistance to V. dahliae. However, the lack of a complete genome sequence with a high-quality assembly and complete genomic annotations for V. dahliae has limited these studies. In this study, we produced a full genomic assembly for V. dahliae VD991 using Nanopore sequencing technology, consisting of 35.77 Mb across eight pseudochromosomes and with a GC content of 53.41%. Analysis of the genome completeness assessment (BUSCO alignment: 98.62%; Illumina reads alignment: 99.17%) indicated that our efforts resulted in a nearly complete and high-quality genomic assembly. We selected 25 species closely related to V. dahliae for evolutionary analysis, confirming the evolutionary relationship between V. dahliae and related species, and the identification of a possible whole genome duplication event in V. dahliae. The interaction between cotton and V. dahliae was investigated by transcriptome sequencing resulting in the identification of many genes and pathways associated with cotton disease resistance and V. dahliae pathogenesis. These results will provide new insights into the pathogenic mechanisms of V. dahliae and contribute to the cultivation of cotton varieties resistant to Verticillium wilt.
Etiology, effects and management of comorbidities in multiple sclerosis: recent advances

Comorbid conditions commonly affect people with multiple sclerosis (MS). Population-based studies indicate that people with MS have an increased incidence of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and psychiatric disorders as compared to people without MS. People with MS from underrepresented minority and immigrant groups have higher comorbidity burdens. Comorbidities exert effects throughout the disease course, from symptom onset through diagnosis to the end of life. At the individual level, comorbidity is associated with higher relapse rates, greater physical and cognitive impairments, lower health-related quality of life, and increased mortality. At the level of the health system and society, comorbidity is associated with increased health care utilization, costs and work impairment. A nascent literature suggests that MS affects outcomes from comorbidities. Comorbidity management needs to be integrated into MS care, and this would be facilitated by determining optimal models of care.
Antagonistic transcriptome profile reveals potential mechanisms of action on Xanthomonas oryzae pv. oryzicola by the cell-free supernatants of Bacillus velezensis 504, a versatile plant probiotic bacterium

Bacterial leaf streak (BLS) of rice is a severe disease caused by the bacterial pathogen Xanthomonas oryzae pv. oryzicola (Xoc) that has gradually become the fourth major disease on rice in some rice-growing regions in southern China. Previously, we isolated a Bacillus velezensis strain 504 that exhibited apparent antagonistic activity against the Xoc wild-type strain RS105, and found that B. velezensis 504 was a potential biocontrol agent for BLS. However, the underlying mechanisms of antagonism and biocontrol are not completely understood. Here we mine the genomic data of B. velezensis 504, and the comparative transcriptomic data of Xoc RS105 treated by the cell-free supernatants (CFSs) of B. velezensis 504 to define differentially expressed genes (DEGs). We show that B. velezensis 504 shares over 89% conserved genes with FZB42 and SQR9, two representative model strains of B. velezensis, but 504 is more closely related to FZB42 than SQR9, as well as B. velezensis 504 possesses the secondary metabolite gene clusters encoding the essential anti-Xoc agents difficidin and bacilysin. We conclude that approximately 77% of Xoc RS105 coding sequences are differentially expressed by the CFSs of B. velezensis 504, which significantly downregulates genes involved in signal transduction, oxidative phosphorylation, transmembrane transport, cell motility, cell division, DNA translation, and five physiological metabolisms, as well as depresses an additional set of virulence-associated genes encoding the type III secretion, type II secretion system, type VI secretion system, type IV pilus, lipopolysaccharides and exopolysaccharides. We also show that B. velezensis 504 is a potential biocontrol agent for bacterial blight of rice exhibiting relative control efficiencies over 70% on two susceptible cultivars, and can efficiently antagonize against some important plant pathogenic fungi including Colletotrichum siamense and C. australisinense that are thought to be the two dominant pathogenic species causing leaf anthracnose of rubber tree in Hainan province of China. B. velezensis 504 also harbors some characteristics of plant growth-promoting rhizobacterium such as secreting protease and siderophore, and stimulating plant growth. This study reveals the potential biocontrol mechanisms of B. velezensis against BLS, and also suggests that B. velezensis 504 is a versatile plant probiotic bacterium.
Immunotherapy-related adverse events in real-world patients with advanced non-small cell lung cancer on chemoimmunotherapy: a Spinnaker study sub-analysis

Background The Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors. Methods The Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres. Data were collected on patient characteristics, survival outcomes, frequency and severity of irAEs, and peripheral immune-inflammatory blood markers, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). Results A total of 308 patients were included; 132 (43%) experienced any grade irAE, 100 (32%) Grade 1–2, and 49 (16%) Grade 3–4 irAEs. The median OS in patients with any grade irAES was significantly longer (17.5 months [95% CI, 13.4–21.6 months]) than those without (10.1 months [95% CI, 8.3–12.0 months]) (p<0.001), either if Grade 1–2 (p=0.003) or Grade 3–4 irAEs (p=0.042). The median PFS in patients with any grade irAEs was significantly longer (10.1 months [95% CI, 9.0–11.2 months]) than those without (6.1 months [95% CI, 5.2–7.1 months]) (p<0.001), either if Grade 1–2 (p=0.011) or Grade 3–4 irAEs (p=0.036). A higher rate of irAEs of any grade and specifically Grade 1–2 irAEs correlated with NLR <4 (p=0.013 and p=0.018), SII <1,440 (p=0.029 ad p=0.039), response to treatment (p=0.001 and p=0.034), a higher rate of treatment discontinuation (p<0.00001 and p=0.041), and the NHS-Lung prognostic classes (p=0.002 and p=0.008). Conclusions These results confirm survival outcome benefits in patients with irAEs and suggest a higher likelihood of Grade 1–2 irAEs in patients with lower NLR or SII values or according to the NHS-Lung score.
Symptoms of and coping strategies for music performance anxiety through different time periods

Music performance anxiety (MPA) manifests itself at mental, physiological, and behavioral levels. The present study investigated how the experience of the three levels of symptoms changes over time, and how musicians cope with these temporal changes in MPA symptoms. To this end, we conducted a questionnaire survey in which 38 student musicians freely commented on their experiences of mental and physical changes, as well as their coping strategies for these changes. This was examined during five different time periods around public performance, extending from the beginning of the preparation for a public performance until shortly before the next public performance. The free-text comments obtained from the questionnaire were analyzed thematically and classified into different response themes. We then examined the temporal changes in the frequency of comments on each response theme. We further conducted a semi-structured interview involving eight musicians to explore the responses to the questionnaire in greater detail. We analyzed the contents of the free-text comments obtained from the questionnaire and the interview for each response theme, focusing on the most frequently mentioned sub-themes. The results indicate that musicians started to experience mental MPA symptoms (e.g., negative feelings) as soon as they began to prepare for public performance. To cope with mental symptoms, musicians employed mental strategies such as positive thinking/self-talk and concentration both before and during public performance. The experience of physiological MPA symptoms (e.g., increased heart rate) peaked shortly before public performance and remained throughout performance. To cope with a variety of physiological symptoms, musicians employed physical strategies, especially deep breathing and exercise, shortly before public performance. In contrast, behavioral MPA symptoms (e.g., tremor) were experienced mostly during public performance. Some musicians also reported experiencing the actual impairment of performance quality. To avoid this, musicians employed a variety of practicing techniques (e.g., playing at a slower tempo) during the preparation for public performance and performing techniques (e.g., paying attention to expressions) during public performance. Together, the present findings indicate that mental, physiological, and behavioral symptoms of MPA exhibit differential timelines and that musicians effectively utilize different coping strategies according to the temporal changes in MPA symptoms.
Large-scale analysis of putative plasmids in clinical multidrug-resistant Escherichia coli isolates from Vietnamese patients

Introduction In the past decades, extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Escherichia coli isolates have been detected in Vietnamese hospitals. The transfer of antimicrobial resistance (AMR) genes carried on plasmids is mainly responsible for the emergence of multidrug-resistant E. coli strains and the spread of AMR genes through horizontal gene transfer. Therefore, it is important to thoroughly study the characteristics of AMR gene-harboring plasmids in clinical multidrug-resistant bacterial isolates. Methods The profiles of plasmid assemblies were determined by analyzing previously published whole-genome sequencing data of 751 multidrug-resistant E. coli isolates from Vietnamese hospitals in order to identify the risk of AMR gene horizontal transfer and dissemination. Results The number of putative plasmids in isolates was independent of the sequencing coverage. These putative plasmids originated from various bacterial species, but mostly from the Escherichia genus, particularly E. coli species. Many different AMR genes were detected in plasmid contigs of the studied isolates, and their number was higher in CR isolates than in ESBL-producing isolates. Similarly, the blaKPC-2, blaNDM-5, blaOXA-1, blaOXA-48, and blaOXA-181 β-lactamase genes, associated with resistance to carbapenems, were more frequent in CR strains. Sequence similarity network and genome annotation analyses revealed high conservation of the β-lactamase gene clusters in plasmid contigs that carried the same AMR genes. Discussion Our study provides evidence of horizontal gene transfer in multidrug-resistant E. coli isolates via conjugative plasmids, thus rapidly accelerating the emergence of resistant bacteria. Besides reducing antibiotic misuse, prevention of plasmid transmission also is essential to limit antibiotic resistance.
HT-B and S-RNase CRISPR-Cas9 double knockouts show enhanced self-fertility in diploid Solanum tuberosum

The Gametophytic Self-Incompatibility (GSI) system in diploid potato (Solanum tuberosum L.) poses a substantial barrier in diploid potato breeding by hindering the generation of inbred lines. One solution is gene editing to generate self-compatible diploid potatoes which will allow for the generation of elite inbred lines with fixed favorable alleles and heterotic potential. The S-RNase and HT genes have been shown previously to contribute to GSI in the Solanaceae family and self-compatible S. tuberosum lines have been generated by knocking out S-RNase gene with CRISPR-Cas9 gene editing. This study employed CRISPR-Cas9 to knockout HT-B either individually or in concert with S-RNase in the diploid self-incompatible S. tuberosum clone DRH-195. Using mature seed formation from self-pollinated fruit as the defining characteristic of self-compatibility, HT-B-only knockouts produced little or no seed. In contrast, double knockout lines of HT-B and S-RNase displayed levels of seed production that were up to three times higher than observed in the S-RNase-only knockout, indicating a synergistic effect between HT-B and S-RNase in self-compatibility in diploid potato. This contrasts with compatible cross-pollinations, where S-RNase and HT-B did not have a significant effect on seed set. Contradictory to the traditional GSI model, self-incompatible lines displayed pollen tube growth reaching the ovary, yet ovules failed to develop into seeds indicating a potential late-acting self-incompatibility in DRH-195. Germplasm generated from this study will serve as a valuable resource for diploid potato breeding.