Case report: Ureteric bud intestinal-type adenocarcinoma involving the cervix was misdiagnosed as a large cervical fibroid.

Background: Malignant tumors of the ureteric bud are not common, and cervical involvement is even rarer. So far, there have been no such cases in the literature. Case summary: A 50-year-old woman developed intermittent light bleeding in the past 7 months and lower abdominal pain in the past 2 months. The human papillomavirus 16 (HPV) DNA, P16 chemical staining, thinPrep cytology test (TCT), and cervical and cervical canal tissue biopsy were all negative. Pelvic color Doppler ultrasound exhibited incomplete mediastinal uterus and heterogeneous echo from the cervical canal to the posterior wall of the cervix. Pelvic contrast-enhanced CT showed left cervical mass, left retroperitoneal mass, absence of the left kidney, and mediastinal uterus. An increase in human epididymal protein 4 (HE4) (133.6 pmol/L) was detected, while other tumor markers were at normal levels. Based on these examination results, a diagnosis of "cervical fibroids, left retroperitoneal mass, incomplete mediastinal uterus, left kidney deficiency"[SIC] was conducted, and expanded hysterectomy, right adnexectomy, and left retroperitoneal mass resection were performed. Through intraoperative rapid pathological diagnosis, postoperative pathological diagnosis combined with the re-evaluation of laboratory, and imaging and intraoperative examination results, the patient was diagnosed with ureteric bud intestinal-type adenocarcinoma involving the cervix. The patient has been tracked and followed up for approximately 11 months. She underwent six courses of chemotherapy. At present, the medication has been discontinued for 4 months, and there is no recurrence, metastasis, or deterioration of the tumor. Conclusion: For large masses of the cervix, it is feasible for the operation to be performed, improving the prognosis. There were a few limitations. A preoperative aspiration biopsy of masses was not performed to differentiate benign from malignant. Preoperative urography was not performed to clarify the function of the malformed urinary system structure. Partial cystectomy should be performed simultaneously with the resection of the ureteric bud for intestinal-type adenocarcinoma. In this case, a partial cystectomy was not performed, which can only be compensated with postoperative chemotherapy. Moreover, this patient did not undergo genetic screening, and it is currently unclear whether there are any genetic mutations associated with ureteric bud intestinal adenocarcinoma.

Quercetin attenuates cisplatin-induced mitochondrial apoptosis via PI3K/Akt mediated inhibition of oxidative stress in pericytes and improves the blood labyrinth barrier permeability.

Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc. Oxidative stress levels, mitochondrial function and endothelial barrier changes were observed in vitro by using DCFH-DA probe detection, flow cytometry, JC-1 probe, immunofluorescence and the establishment in vitro BLB models, etc. QU pretreatment activates the PI3K/AKT signaling pathway, inhibits CDDP-induced oxidative stress, protects mitochondrial function, and reduces mitochondrial apoptosis in PCs. However, PI3K/AKT specific inhibitor (LY294002) partially reverses the protective effects of QU. In addition, in vitro BLB models were established by coculturing PCs and endothelial cells (ECs), which suggests that QU both reduces the CDDP-induced apoptosis in PCs and improves the endothelial barrier permeability. On the whole, the research findings suggest that QU can be used as a novel treatment to reduce CDDP-induced ototoxicity.

Fitness difference between two synonymous mutations of Phytophthora infestans ATP6 gene.

BACKGROUND: Sequence variation produced by mutation provides the ultimate source of natural selection for species adaptation. Unlike nonsynonymous mutation, synonymous mutations are generally considered to be selectively neutral but accumulating evidence suggests they also contribute to species adaptation by regulating the flow of genetic information and the development of functional traits. In this study, we analysed sequence characteristics of ATP6, a housekeeping gene from 139 Phytophthora infestans isolates, and compared the fitness components including metabolic rate, temperature sensitivity, aggressiveness, and fungicide tolerance among synonymous mutations. RESULTS: We found that the housekeeping gene exhibited low genetic variation and was represented by two major synonymous mutants at similar frequency (0.496 and 0.468, respectively). The two synonymous mutants were generated by a single nucleotide substitution but differed significantly in fitness as well as temperature-mediated spatial distribution and expression. The synonymous mutant ending in AT was more common in cold regions and was more expressed at lower experimental temperature than the synonymous mutant ending in GC and vice versa. CONCLUSION: Our results are consistent with the argument that synonymous mutations can modulate the adaptive evolution of species including pathogens and have important implications for sustainable disease management, especially under climate change.

Evaluating the contribution of historical and contemporary temperature to the oospore production of self-fertile Phytophthora infestans.

Reproductive systems play an important role in the ecological function of species, but little is known about how climate change, such as global warming, may affect the reproductive systems of microbes. In this study, 116 Phytophthora infestans isolates sampled from five different altitudes along a mountain were evaluated under five temperature regimes to determine the effects of historical and experimental temperature on the reproductive system of the pathogen. Both altitude, a proxy for historical pathogen adaptation to temperature, and temperature used in the experiment affected the sexual reproduction of the pathogen, with experimental temperature, that is, contemporary temperature, playing a role several times more important than historical temperature. Furthermore, the potential of sexual reproduction, measured by the number of oospores quantified, increased with the temperature breadth (i.e., difference between the highest and lowest temperature at which sexual reproduction takes place) of the pathogen and reached the maximum at the experimental temperature of 21°C, which is higher than the annual average temperature in many potato-producing areas. The results suggest that rising air temperature associated with global warming may increase the potential of sexual reproduction in P. infestans. Given the importance of sexuality in pathogenicity and ecological adaptation of pathogens, these results suggest that global warming may increase the threat of P. infestans to agricultural production and other ecological services and highlight that new epidemiological strategies may need to be implemented for future food security and ecological resilience.

Moderating role of family functioning and resource support in the relationship between career calling and academic burnout among Chinese medical students during the controlled COVID-19 pandemic: a cross-sectional study.

PURPOSE: This cross-sectional study aims to assess the level of academic burnout among Chinese medical students during the controlled COVID-19 pandemic and identify the potential demographic factors affecting academic burnout. It also explored the relationship between career calling, family functioning, resource support, and academic burnout, as well as investigated whether family functioning and resource support could moderate the relationship between career calling and academic burnout among Chinese medical students. METHODS: The study was conducted in five Chinese cities in 2021. A total of 3614 valid questionnaires were collected to assess the relationship between academic burnout, career calling, family functioning, and resource support, and determine whether demographic factors contribute to academic burnout. Hierarchical multiple regression analysis was used to explore factors correlated with academic burnout and test the moderating effect of family functioning and resource support on the relationship between career calling and academic burnout. RESULTS: The mean academic burnout score was 3.29 ± 1.17. Sex, major, academic performance ranking, monthly living expenses, physical health, and sleep quality significantly affected academic burnout (p < 0.05). Academic burnout was negatively correlated with career calling, resource support, and family functioning. Family functioning and resource support moderated the relationship between career calling and academic burnout. Simple slope analysis revealed that high family functioning and resource support strengthened the impact of career calling on academic burnout. CONCLUSIONS: Most medical students in China experienced relatively high levels of academic burnout during the controlled COVID-19 pandemic. Furthermore, specific demographic factors contribute to academic burnout. Family functioning and resource support moderate the relationship between career calling and academic burnout. These findings emphasize the importance of implementing career-calling education, supplementing family functioning in the form of school support, and providing sufficient smart learning resources among medical students in the post-pandemic era.

The results revealed that career calling was strongly and negatively correlated with academic burnout during the controlled COVID-19 pandemic.High family functioning and resource support strengthened the impact of career calling on academic burnout during the controlled COVID-19 pandemic.

PGC-1α affects cochlear pericytes migration in noise-exposed mice.

OBJECTIVE: The study aimed to observe the effects of noise exposure on the pericytes of the cochlear stria vascularis (SV) in mice and to investigate its molecular mechanism. METHOD: Male C57BL/6J mice aged 6-8 weeks were used as the subjects. Auditory Brainstem Response (ABR) was used to assess hearing loss. Hematoxylin and Eosin (HE) staining was conducted to observe morphological alterations in the SV. Immunofluorescence combined with transmission electron microscopy (TEM) was used to scrutinize changes in pericytes following acoustic injury. Western blotting (WB) was used to assess the expression variations of the migration-related protein Osteopontin (OPN). Evans Blue assay was performed to evaluate the permeability of the blood labyrinth barrier (BLB). 4-Hydroxynonenal (4-HNE) staining, in conjunction with measurements of Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Catalase (CAT) content, was used to ascertain whether oxidative stress injury occurred in the SV. WB, combined with immunofluorescence, was used to examine alterations in the expression of proliferator-activated receptor-gamma coactivator 1α (PGC-1α) in the SV and pericytes. RESULTS: Noise exposure resulted in permanent hearing loss in C57BL/6J mice, accompanied by SV swelling, migration of pericytes from their vascular attachments, BLB leakage, elevated oxidative stress levels in the SV, and reduced expression of PGC-1α on both the SV and migrating pericytes. CONCLUSION: Noise exposure may potentially increase oxidative stress levels in the SV, downregulate the expression levels of PGC-1α, promote pericytes migration, and subsequently lead to an elevation in BLB permeability.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature.

Objective: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. Methods: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. Results: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. Conclusion: These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Moderating Role of Peer Pressure and Positive Learning Environment Between Career Calling and Academic Procrastination in Chinese Medical Students During Controlled COVID-19 Pandemic: A Cross-Sectional Study.

Purpose: The COVID-19 pandemic sets specific circumstances that may accelerate academic procrastination behavior of medical students. Career calling is a protective factor that fights against academic procrastination and may further improve medical students' mental health and academic achievement. This study aims to determine the status of Chinese medical students' academic procrastination during controlled COVID-19 pandemic. Moreover, the study investigates the relationships and mechanisms among career calling, peer pressure, a positive learning environment, and academic procrastination. Patients and Methods: Data were collected from several Chinese medical universities through an anonymous cross-sectional survey of 3614 respondents (effective response rate = 60.0%). Using online questionnaires to collect the data and IBM SPSS Statistics 22.0 for statistical analysis. Results: The average score of academic procrastination of Chinese medical students was 2.62±0.86. This study proved the usage of peer pressure and positive learning environment as moderating roles of relationship between career calling and academic procrastination. Career calling was negatively correlated with academic procrastination (r = -0.232, p < 0.01), while it was positively correlated with peer pressure (r = 0.390, p < 0.01) and a positive learning environment (r = 0.339, p < 0.01). Moreover, academic procrastination was negatively correlated with peer pressure (r = -0.279, p < 0.01) and a positive learning environment (r = -0.242, p < 0.01). Peer pressure was positively correlated with a positive learning environment (r = 0.637, p < 0.01). Conclusion: The findings emphasize the importance of constructive peer pressure and a positive learning environment that discourages academic procrastination. Educators should highlight medical career calling education by offering related courses to fight against academic procrastination.

The Adaptive Evolution in the Fall Armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) Revealed by the Diversity of Larval Gut Bacteria.

Insect gut microbes have important roles in host feeding, digestion, immunity, development, and coevolution with pests. The fall armyworm, Spodoptera frugiperda (Smith, 1797), is a major migratory agricultural pest worldwide. The effects of host plant on the pest's gut bacteria remain to be investigated to better understand their coevolution. In this study, differences in the gut bacterial communities were examined for the fifth and sixth instar larvae of S. frugiperda fed on leaves of different host plants (corn, sorghum, highland barley, and citrus). The 16S rDNA full-length amplification and sequencing method was used to determine the abundance and diversity of gut bacteria in larval intestines. The highest richness and diversity of gut bacteria were in corn-fed fifth instar larvae, whereas in sixth instar larvae, the richness and diversity were higher when larvae were fed by other crops. Firmicutes and Proteobacteria were dominant phyla in gut bacterial communities of fifth and sixth instar larvae. According to the LDA Effect Size (LEfSe) analysis, the host plants had important effects on the structure of gut bacterial communities in S. frugiperda. In the PICRUSt2 analysis, most predicted functional categories were associated with metabolism. Thus, the host plant species attacked by S. frugiperda larvae can affect their gut bacterial communities, and such changes are likely important in the adaptive evolution of S. frugiperda to host plants.

Study on the mechanism of Fufang E'jiao Jiang on precancerous lesions of gastric cancer based on network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang E'jiao Jiang (FEJ) is a prominent traditional Chinese medicine prescription, which consists of Asini Corii Colla (Donkey-hide gelatin prepared by stewing and concentrating from the hide of Equus asinus Linnaeus., ACC), Codonopsis Radix (the dried roots of Codonopsis pilosula (Franch.) Nannf., CR), Ginseng Radix et Rhizoma Rubra (the steamed and dried root of Panax ginseng C.A. Mey., GRR), Crataegi Fructus (the mature fruits of Crataegus pinnatifida Bunge., CF), and Rehmanniae Radix Praeparata (the steamed and sun dried tuber of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey., RRP). It is a popularly used prescription for "nourishing Qi and nourishing blood". AIM OF THE STUDY: To explore the potential mechanism of FEJ on precancerous lesion of gastric cancer in rats by combining network pharmacology and metabolomics. METHODS: Traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine were used to identify the ingredients and potential targets of FEJ. GeneCards database was used to define PLGC-associated targets. We built a herb-component-disease-target network and analyzed the protein-protein interaction network. Underlying mechanisms were identified using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, 40% ethanol, N-methyl-N'-nitro-N-nitroguanidine and irregular eating were used to establish PLGC rats model. We also evaluated the efficacy of FEJ on MNNG-induced PLGC rats by body weight, histopathology, blood routine and cytokine levels, while the predicted pathway was determined by the Western blot. Ultra-performance liquid chromatography-tandem mass spectrometry-based serum non-targeted metabolomics was used to select potential biomarkers and relevant pathways for FEJ in the treatment of PLGC. RESULTS: Network pharmacology showed that FEJ exhibited anti-PLGC effects through regulating ALB, TNF, VEGFA, TP53, AKT1 and other targets, and the potential pathways mainly involved cancer-related, TNF, PI3K-AKT, HIF-1, and other signaling pathways. Animal experiments illustrated that FEJ could suppress inflammation, regulate gastrointestinal hormones, and inhibit the expression of PI3K/AKT/HIF-1α pathway-related proteins. Based on serum non-targeted metabolomics analysis, 12 differential metabolites responding to FEJ treatment were identified, and metabolic pathway analysis showed that the role of FEJ was concentrated in 6 metabolic pathways. CONCLUSION: Based on network pharmacology, animal experiments and metabolomics, we found that FEJ might ameliorate gastric mucosal injury in PLGC rats by regulating gastrointestinal hormones and inhibiting inflammation, and its mechanism of action is related to the inhibition of excessive activation of PI3K/AKT/HIF-1α signaling pathway and regulation of disorders of body energy metabolism. This comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine.

The structure and assembly of rhizobacterial communities are influenced by poplar genotype.

The interaction between plants and microbes dominates plant growth and fitness in specific environments. The study of the relationship between plant genotypes and rhizobacterial community structure would provide a deep insight into the recruitment strategies of plants toward soil bacteria. In this study, three genotypes of 18-year-old mature poplar (H1, H2, and H3) derived from four different parents were selected from a germplasm nursery of Populus deltoides. Rhizosphere soil carbon, nitrogen, and phosphorus properties as well as the 16S rDNA sequences of rhizobacterial communities were analyzed to determine the relationship between poplar genotypes and rhizobacterial communities assembly. The results showed there were significant differences in the diversity (Chao1, ACE index, and Shannon index) of rhizobacterial communities between H1 and H2, as well as between H2 and H3, but no difference between H1 and H3. Principal component analysis also revealed a similar structure of rhizobacterial communities between H1 and H3, whereas the rhizobacterial communities of H2 demonstrated significant differences from H1 and H3. Linear discriminant effect size analysis indicated that there were 11 and 14 different biomarkers in the H1 and H3 genotype, respectively, but 42 in the H2 genotype. Co-occurrence network analysis indicated that the rhizobacterial communities of H2 had a distinct network structure compared to those of the other two genotypes, whereas H1 and H3 had a similar pattern of co-occurrence network. Threshold indicator taxa analysis revealed that 63 genera responded significantly to NO3 --N content and 58 genera to NH4 +-N/NO3 --N ratio. Moreover, the stochastic assembly process was found to be decreased with increasing NO3 --N content and fluctuated with increasing NH4 +-N/NO3 --N ratio. All results indicated that the structure of poplar rhizobacterial communities were influenced by host genotypes, and available nitrogen might play a dominant role in the assembly of rhizobacterial communities. This study would promote the future selection and utilization of rhizobacteria in poplar breeding.

[Role of Cav1.2 in cisplatin induced apoptosis of cochlear spiral ganglion neurons in C57BL/6J mice].

Objective: To investigate the role of Cav1.2 and its possible mechanism in the apoptosis of cochlear spiral ganglion neurons(SGNs) induced by cisplatin (CDDP) in C57BL/6J mice. Methods: Animal experiment: 8-week-old male C57BL/6J mice were randomly divided into the following two groups (10 mice/group) : normal saline group (Control group) and Cisplatin group (Cisplatin group). The Control group received daily intraperitoneal injections of normal saline, Cisplatin group was injected with cisplatin intraperitoneally at a dose of 3 mg/kg at the first 4 days of each cycle, and normal saline was injected daily at the last 10 days,repeat for 3 cycles. After administration, auditory threshold was detected by auditory brainstem response (ABR). Blood samples were collected from inner canthus of mice, and cochlea was cut off from neck. SOD and MDA kits were used to detect SOD activity and MDA content in serum and cochlea tissues. The expressions of apoptosis proteins in cochlear tissues were detected by Western blot. Morphological changes of spiral ganglion in mouse cochlea were observed by hematoxylin-eosin (HE) staining. TUNEL staining was used to observe the apoptosis of SGNs in cochlea of mice. The distribution and expression of Cav1.2 in SGNs of cochlea were observed by immunofluorescence. Cell experiment: Primary cultured SGNs were randomly divided into: control group (Control), solvent group (DMSO), Cav1.2 blocker group (N), cisplatin group, cisplatin and Cav1.2 blocker co-incubation group (Cisplatin+N). 5 µmol/L cisplatin was selected to treat SGNs based on the results of CCK8. Western blot was used to detect the protein expressions of Cav1.2.and apoptotic proteins. Hoechst33342 staining was used to observe the apoptosis of each group. Flow cytometry was used to detect the apoptosis rate of each group. Mitochondrial superoxide indicator (MitoSOXTM-Red) was used to detect the ROS release of mitochondria. Results: Animal experiments: Compared to the Control group, the hearing threshold was increased in Cisplatin group (P<0.01), the content of MDA in serum and cochlea tissues, apoptosis protein Cleaved caspase-3, Bax protein level, TUNEL positive rate, Cav1.2 protein expression level were increased significantly (P<0.05, P<0.01); the activity of SOD in serum and cochlear tissue, anti-apoptotic protein bcl-2 protein level and SGCs density in cochlear tissue were decreased significantly (P<0.05, P<0.01). Cell tests: Compared with the Control group, the expression of Cav1.2, apoptosis rate, Cleaved caspase-3, Bax protein level, intracellular calcium ion concentration, and ROS release were increased significantly only in Cisplatin group (P<0.05, P<0.01). The levels of bcl-2 protein and mitochondrial membrane potential were decreased significantly (P<0.01). Cav1.2 blockers could partially reverse the above changes (P<0.05). Conclusion: Cisplatin may increase intracellular Ca2+ concentration through up-regulation of Cav1.2, and then damage mitochondria, causing oxidative stress injury of SGNs and inducing neuronal apoptosis.

Proactive personality and critical thinking in Chinese medical students: The moderating effects of psychological safety and academic self-efficacy.

Objectives: This study aimed to identify the relationship among proactive personality, psychological safety, academic self-efficacy and critical thinking, and to further explore whether psychological safety and academic self-efficacy could be a moderator in the association between proactive personality and critical thinking among Chinese medical students. Materials and methods: The cross-sectional study was carried out from October to December 2020 in China. Totally, 5,920 valid responses were collected at four Chinese medical universities. Critical thinking, proactive personality, psychological safety, academic self-efficacy and demographic factors were assessed through questionnaires. Hierarchical multiple regression was used to identify interrelationship clusters among variables. Simple slope analyses were performed to explore the moderating effects of psychological safety and academic self-efficacy. Results: The mean score of critical thinking among medical students was 3.85 ± 0.61. Proactive personality, psychological safety, and academic self-efficacy were shown to be important factors for critical thinking. Psychological safety and academic self-efficacy moderated the association between proactive personality and critical thinking. A simple slope analysis showed that high psychological safety and academic self-efficacy weakened the impact of proactive personality on critical thinking. Conclusion: Most medical students surveyed in China might have relatively high levels of critical thinking. Psychological safety and academic self-efficacy moderated the association between proactive personality and critical thinking. More interventions related to psychological safety and academic self-efficacy will be helpful to improve critical thinking among Chinese medical students.

Corrigendum: Single amino acid substitution in the DNA repairing gene radiation-sensitive 4 contributes to ultraviolet tolerance of a plant pathogen.

[This corrects the article DOI: 10.3389/fmicb.2022.927139.].

Genetic variation along an altitudinal gradient in the Phytophthora infestans effector gene Pi02860.

Effector genes, together with climatic and other environmental factors, play multifaceted roles in the development of plant diseases. Understanding the role of environmental factors, particularly climate conditions affecting the evolution of effector genes, is important for predicting the long-term value of the genes in controlling agricultural diseases. Here, we collected Phytophthora infestans populations from five locations along a mountainous hill in China and sequenced the effector gene Pi02860 from >300 isolates. To minimize the influence of other ecological factors, isolates were sampled from the same potato cultivar on the same day. We also expressed the gene to visualise its cellular location, assayed its pathogenicity and evaluated its response to experimental temperatures. We found that Pi02860 exhibited moderate genetic variation at the nucleotide level which was mainly generated by point mutation. The mutations did not change the cellular location of the effector gene but significantly modified the fitness of P. infestans. Genetic variation and pathogenicity of the effector gene were positively associated with the altitude of sample sites, possibly due to increased mutation rate induced by the vertical distribution of environmental factors such as UV radiation and temperature. We further found that Pi02860 expression was regulated by experimental temperature with reduced expression as experimental temperature increased. Together, these results indicate that UV radiation and temperature are important environmental factors regulating the evolution of effector genes and provide us with considerable insight as to their future sustainable action under climate and other environmental change.

Single Amino Acid Substitution the DNA Repairing Gene Radiation-Sensitive 4 Contributes to Ultraviolet Tolerance of a Plant Pathogen.

To successfully survive and reproduce, all species constantly modify the structure and expression of their genomes to cope with changing environmental conditions including ultraviolet (UV) radiation. Thus, knowledge of species adaptation to environmental changes is a central theme of evolutionary studies which could have important implication for disease management and social-ecological sustainability in the future but is generally insufficient. Here, we investigated the evolution of UV adaptation in organisms by population genetic analysis of sequence structure, physiochemistry, transcription, and fitness variation in the radiation-sensitive 4 (RAD4) gene of the Irish potato famine pathogen Phytophthora infestans sampled from various altitudes. We found that RAD4 is a key gene determining the resistance of the pathogen to UV stress as indicated by strong phenotype-genotype-geography associations and upregulated transcription after UV exposure. We also found conserved evolution in the RAD4 gene. Only five nucleotide haplotypes corresponding to three protein isoforms generated by point mutations were detected in the 140 sequences analyzed and the mutations were constrained to the N-terminal domain of the protein. Physiochemical changes associated with non-synonymous mutations generate severe fitness penalty to mutants, which are purged out by natural selection, leading to the conserved evolution observed in the gene.

Clinical Efficacy of Levothyroxine Sodium plus I 131 in the Treatment of Patients with Thyroidectomy and Its Effect on the Levels of Thyroglobulin and Thyrotropin.

Objective: This study was to evaluate the clinical efficacy of levothyroxine sodium tablets combined with I 131 in the treatment of patients after thyroidectomy and the effect on thyroglobulin (Tg) and thyroid stimulating hormone (TSH) levels. Methods: 80 patients with differentiated thyroid cancer who required thyroidectomy after surgery between July 2019 and January 2021 were recruited for prospective study, 40 patients in the control group received levothyroxine sodium tablets, and 40 patients in the experimental group received levothyroxine sodium treatment plus I 131 treatment. Treatment effect, serum Tg and TSH levels, and relapse were measured. Results: The removal rate of residual thyroid tissue in the experimental group (87.50%) was significantly higher than that in the control group (57.50%) (P < 0.05). Levothyroxine sodium tablets plus I 131 was associated with a significantly higher efficacy versus levothyroxine sodium tablets (P < 0.05). There were no significant differences in the serum Tg levels between the two groups before treatment (P > 0.05). After treatment, the serum Tg levels in both groups were significantly decreased, and levothyroxine sodium tablets plus I 131 resulted in a significantly lower Tg level versus levothyroxine sodium tablets (P < 0.05). Before treatment, the two groups showed similar TSH levels (P > 0.05). After treatment, patients receiving levothyroxine sodium tablets plus I 131 had a significantly greater increase in the TSH levels versus levothyroxine sodium tablets (P < 0.05). The recurrence rate of the experimental group was lower than that of the control group (P < 0.05). Conclusion: Levothyroxine sodium tablets plus I 131 for post-operative patients with differentiated thyroid cancer enhance the removal rate of residual thyroid tissue, effectively reduce serum Tg level, and increase TSH level, with significant therapeutic effects, low recurrence rates, and a high safety profile.

Elevating Air Temperature May Enhance Future Epidemic Risk of the Plant Pathogen Phytophthora infestans.

Knowledge of pathogen adaptation to global warming is important for predicting future disease epidemics and food production in agricultural ecosystems; however, the patterns and mechanisms of such adaptation in many plant pathogens are poorly understood. Here, population genetics combined with physiological assays and common garden experiments were used to analyze the genetics, physiology, and thermal preference of pathogen aggressiveness in an evolutionary context using 140 Phytophthora infestans genotypes under five temperature regimes. Pathogens originating from warmer regions were more thermophilic and had a broader thermal niche than those from cooler regions. Phenotypic plasticity contributed ~10-fold more than heritability measured by genetic variance. Further, experimental temperatures altered the expression of genetic variation and the association of pathogen aggressiveness with the local temperature. Increasing experimental temperature enhanced the variation in aggressiveness. At low experimental temperatures, pathogens from warmer places produced less disease than those from cooler places; however, this pattern was reversed at higher experimental temperatures. These results suggest that geographic variation in the thermal preferences of pathogens should be included in modeling future disease epidemics in agricultural ecosystems in response to global warming, and greater attention should be paid to preventing the movement of pathogens from warmer to cooler places.

Corrigendum: Mitochondrial genome contributes to the thermal adaptation of the oomycete Phytophthora infestans.

[This corrects the article DOI: 10.3389/fmicb.2022.928464.].