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Xing-Xi Pan,1 Li-Hua Tong,1 Yong-Fa Chen,1 Fei-Long Li,1 Wu-Bing Tang,1 Ya-Jie Liu,2 Wen Yang11Department of Oncology, Nanhai Hospital Affiliated to Southern Medical University, Foshan, Guangdong 528200, People’s Republic of China; 2Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, People’s Republic of ChinaObjective: This study aimed to establish a simplified T classification based on the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for nasopharyngeal carcinoma (NPC).Methods: In total, 325 patients with NPC were included in this study. All patients underwent magnetic resonance imaging, and the staging criteria were recorded. These patients were subjected to staging with the 8th edition of the UICC/AJCC staging system for NPC.Results: Involvement of the oropharynx, nasal cavity, adjacent soft tissue (medial pterygoid, lateral pterygoid, and prevertebral muscles), cervical vertebra, orbit, and hypopharynx were always accompanied by other equivalently or more advanced T-stage classifications. All cases with involvement of the paranasal sinuses showed skull base erosion. The majority of cases with involvement of the pterygoid structure showed skull base erosion.Conclusion: According to the simplification principle, the following new T classification based on the 8th edition of the UICC/AJCC staging system was established: T1, tumor confined to nasopharynx, or beyond the nasopharynx without parapharyngeal involvement; T2, tumor with extension to the parapharyngeal space; T3, tumor with infiltration to bony structures at the skull base; T4, tumor with intracranial extension, involvement of the cranial nerves or parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. Validation with a large series of patients is needed.Keywords: nasopharyngeal cancer, TNM staging system, T classification

East Asian continental outflows with PM 2.5 , O 3 , and other species may determine the baseline conditions and affect the air quality in downwind areas via long-range transport (LRT). To gain insight into the impact and spatiotemporal characteristics of airborne pollutants in East Asian continental outflows, a versatile multicopter drone sounding platform was used to simultaneously observe PM 2.5 , O 3 , CO 2 , and meteorological variables (temperature, specific humidity, pressure, and wind vector) above the northern tip of Taiwan, Cape Fuiguei, which often encounters continental outflows during winter monsoon periods. By coordinating hourly high-spatial-resolution profiles provided by drone soundings, WRF/CMAQ model air quality predictions, HYSPLIT-simulated backward trajectories, and MERRA-2 reanalysis data, we analyzed two prominent phenomena of airborne pollutants in continental outflows to better understand their physical/chemical characteristics. First, we found that pollutants were well mixed within a sounding height of 500 m when continental outflows passed through and completely enveloped Cape Fuiguei. Eddies induced by significant fluctuations in wind speeds coupled with minimal temperature inversion and LRT facilitated vertical mixing, possibly resulting in high homogeneity of pollutants within the outflow layer. Second, the drone soundings indicated exceptionally high O 3 concentrations (70-100 ppbv) but relatively low concentrations of PM 2.5 (10-20 μg/m 3 ), CO 2 (420-425 ppmv), and VOCs in some air masses. The low levels of PM 2.5 , CO 2 , and VOCs ruled out photochemistry as the cause of the formation of high-level O 3 . Further coordination of spatiotemporal data with air mass trajectories and O 3 cross sections provided by MERRA-2 suggested that the high O 3 concentrations could be attributed to stratospheric intrusion and advection via continental outflows. High-level O 3 concentrations persisted in the lower troposphere, even reaching the surface, suggesting that stratospheric intrusion O 3 may be involved in the rising trend in O 3 concentrations in parts of East Asia in recent years in addition to surface photochemical factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation. Methods: This is a retrospective cohort study. The clinical data of 399 patients who underwent orthotopic liver transplantation at the First Affiliated Hospital of Nanjing Medical University from January 2016 to September 2020 were retrospectively collected. There were 319 males and 80 females, aged (50.9±10.2) years (range: 10 to 73 years). These patients were divided into the control group (369 cases) and the dexmedetomidine group (30 cases) according to whether dexmedetomidine was continuously pumped intravenously during the operation until the operation ended. The 1∶2 propensity score matching was used to match the preoperative and intraoperative conditions of the two groups of patients, and the caliper width was 0.2. Outcome indicators included intraoperative postreperfusion syndrome, acute kidney injury and pulmonary complications within 7 days after surgery, length of hospital stay, time of stay in ICU, duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival and recurrence-free survival rate after surgery. The independent sample t test, χ 2 test, Mann-Whitney U test or Fisher exact test was used to statistically analyze the data of the two groups of patients, respectively. Survival curves of overall survival and disease-free-survival were plotted by Kaplan-Meier method, and the survival rate and recurrence-free survival rate were compared by Log-rank test. Results: A total of 78 patients were included after propensity score matching, including 26 in the dexmedetomidine group and 52 in the control group. The incidence of acute kidney injury in the dexmedetomidine group within 7 days after surgery was 0 (0/26), significantly lower than that of the control group (21.2%,11/52)(corrected χ 2 =4.776, P =0.029). There were no significant differences in the incidence of intraoperative postreperfusion syndrome and pulmonary complications within 7 days after surgery, length of hospital stay, ICU time, the duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival, and recurrence-free survival rate after surgery between the two groups (all P >0.05). Conclusion: Continuous infusion of dexmedetomidine via intravenous pump during operation may be beneficial in reducing the incidence of acute kidney injury within 7 days after orthotopic liver transplantation.

Macleaya cordata (Willd.) R. Br. is a perennial herbaceous medicinal plant (Papaveraceae) commercially cultivated in China which has been studied for detumescence, detoxification, and insecticidal effect (Lin et al. 2018). In August 2021, anthracnose was observed in 2-year-old M. cordata plants in Benxi county, northeast China (41°45'48″N, 123°69'15″E). Dozens of irregular reddish-brown spots (3-11 mm) were observed on each diseased leaf. The lesions were covered with a layer of gray-white mycelia. As the disease progressed, the spots became necrosis and perforation or they would merged into large lesions, ultimately resulting in wilted leaves (Fig. 1). More than 33% of the plants in a 16-ha field were infected in 2021. The diseased leaves were collected and cut into 3-8 mm pieces, surface-disinfested by immersing them into 1% NaOCl for 2 min, and rinsed three times with sterile distilled water. They were then dried with sterilized absorbent paper, placed on PDA medium amended with chloramphenicol (40 mg/L), and incubated in darkness at 25°C with a 12-h photoperiod. Twenty isolates (BLH1 to 20) were obtained and purified using a single-spore method. Isolate BLH12 was identified and used for the pathogenicity test. Colonies were sparsely fluffy with smooth edges, and gradually became gray to pale orange from the initial white. The underside of the colonies was pale orange towards the center. Conidia were single-celled, cylindrical, and transparent with broadly blunt ends, measuring (15.13 ± 1.14) × (5.80 ± 0.60) μm (n=50). Appressoria were single-celled, brown-to-dark brown, usually elliptical or irregular, and sometimes lobed. Setae were not observed. The isolate was initially identified as Colletotrichum gloeosporioides complex (Prihastuti et al. 2009). The identification was confirmed as described previously (Weir et al. 2012). The rDNA internal transcribed spacer region (OP415560), the glyceraldehyde-3-phosphate dehydrogenase (OP433642), chitin synthase (OP433643), calmodulin (OP433644), actin (OP433645), glutamine synthetase (OP433646), β-tubulin (OP433647), and superoxide dismutase (OP433648) gene sequences were obtained (Carbone & Kohn 1999; Weir et al. 2012), and BLAST searches revealed 99-100% homology with the type culture ICMP 18608 (JX010244, JX010044, JX009683, JX009443, JX009744, JX010078, JX010389, and JX010311). A phylogenetic analysis of combining all loci indicated BLH12 and the type strain of C. aenigma were clustered in one group (Fig. 2). Based on the basis of morphological characteristics and phylogenetic relationships, BLH12 was identified as C. aenigma . For the pathogenicity test, healthy 2-year-old plants were sprayed with a BLH12 spore suspension (1 × 10 5 /mL). Control plants were sprayed with sterile water.There were three replicates (five plants each) per treatment. All plants were incubated at 25°C (12-h photoperiod and 86% relative humidity) and examined after 7 days. The experiment was repeated twice. The inoculated plants showed lesions on the leaf surface, similar to those in the field, whereas the control plants were asymptomatic. The pathogen was successfully reisolated and identified as the methods mentioned above. This fungus reportedly infects the leaves of many woody plants in China (Wang et al. 2020; Zhang et al. 2021). This is the first report of C. aenigma causing anthracnose on M. cordata , which will provide an guideline for developing effective field control practices for the disease.

In this study, we focused on grapevine-endophyte interactions and reprogrammed secondary metabolism in the host plant due to defense against the colonization of endophytes. Thus, the transcriptional responses of tissue cultured grapevine seedlings ( Vitis vinifera L. cv.: Cabernet Sauvignon) to two fungal endophytes Epicoccum layuense R2-21 (Epi R2-21) and Alternaria alternata XHYN2 (Alt XHYN2) at three different time points (6 h, 6 d, 15 d) were analyzed. As expected, a total of 5748 and 5817 differentially expressed genes (DEGs) were separately initiated in Epi R2-21 and Alt XHYN2 symbiotic tissue cultured seedlings compared to no endophyte treatment. The up-regulated DEGs at all time points in Epi R2-21- or Alt XHYN2-treated seedlings were mainly enriched in the flavonoid biosynthesis, phenylpropanoid biosynthesis, phenylalanine metabolism, stilbenoid, diarylheptanoid and gingerol biosynthesis, and circadian rhythm-plant pathways. In addition, the up-regulated DEGs at all sampling times in Alt XHYN2-treated tissue cultured seedlings were enriched in the plant-pathogen interaction pathway, but appeared in Epi R2-21 symbiotic seedlings only after 15 d of treatment. The down-regulated DEGs were not enriched in any KEGG pathways after 6 h inoculation for Epi R2-21 and Alt XHYN2 treatments, but were enriched mainly in photosynthesis-antenna proteins and plant hormone signal transduction pathways at other sampling times. At three different time points, a total of 51 DEGs (all up-regulated, 1.33-10.41-fold) were involved in secondary metabolism, and 22 DEGs (all up-regulated, 1.01-8.40-fold) were involved in defense responses in endophytic fungi symbiotic tissue cultured seedlings. The protein-protein interaction (PPI) network demonstrated that genes encoding CHS ( VIT_10s0042g00920 , VIT_14s0068g00920 , and VIT_16s0100g00910 ) and the VIT_11s0065g00350 gene encoding CYP73A mediated the defense responses, and might induce more defense-associated metabolites. These results illustrated the activation of stress-associated secondary metabolism in the host grapevine during the establishment of fungi-plant endophytism. This work provides avenues for reshaping the qualities and characteristics of wine grapes utilizing specific endophytes and better understanding plant-microbe interactions.

Ligularia fischeri (Ledeb.) is a perennial herbal plant of Compositae that is cultivated commercially in China as a medicinal, ornamental, and edible plant. Leaf spots were observed in 2-year-old L. fischeri in Benxi County of northeast China, in August 2021. Irregular reddish brown spots ranging from 3 to 11 mm were observed on infected leaves, and each leaf had dozens of spots (Fig. 1). As the disease progressed, the diseased spots withered and the centers fell out, and multiple lesions merge into large diseased spots, causing leaf wilting. The roots and stem bases were not infected during the reproductive stage. More than 37% of the plants in a 18 ha field were infected in 2021. The ten diseased leaves were collected and cut into small (3-5 mm) pieces, which were surface-disinfested by immersing into 1% NaOCl for 2 min and rinsing with sterile distilled water three times. The leaf pieces were then placed on acidified potato dextrose agar (PDA) in petri plates and incubated in the dark at 25°C. Twenty isolates with the same morphological characteristics were obtained. Isolates were further purified by starting a new colony for each isolate from a single spore collected from water agar. Isolate TYTW7 was randomly selected for identification and pathogenicity testing. It grew rapidly and produced profuse aerial mycelia with a carmine red underside. The conidiophores had many fertile branches and formed an elongated stipe with a sphaeropedunculate vesicle at the tip. The one-septate conidia were cylindrical and almost straight with parallel walls and rounded ends. Their sizes ranged from 30.35 to 51.76 × 2.93 to 5.01 μm (n = 100) and the pathogens were initially identified as Calonectria sp. (Crous 2002; Crous et al. 2004; Lombard et al. 2015, 2016). Further confirmation of the identification was determined according to published method (Liu and Chen 2017; Shao and Li 2021). The partial gene regions including the translation elongation factor 1-alpha (GenBank accession no. OP290551), histone H3 (OP290552), calmodulin (OP290553) and β-tubulin (OP290554) were obtained, and BLAST searches showed 99-100% homology with the ex-type culture CERC 8952 (MF527049, MF527065, MF527081 and MF527107) and phylogenetic analysis combining all loci revealed that the isolate TYTW7 and the type strain of Ca. montana clustered in one group (Fig. 2). Based on morphological characteristics and phylogenetic analysis, isolate TYTW7 was identified as Ca. Montana . Healthy 2-year-old plants were used for the pathogenicity test. A spore suspension (1×10 5 spores/mL water) was used to inoculate three host plants; sterile water was sprayed on the same number plants serving as a control. The experiment was repeated three times. All plants were incubated at 27±2°C (12h photoperiod) and were evaluated after seven days. The inoculated plants showed lesions on the leaf surface, similar to those in the field, and the control remained symptomless. The pathogens were successfully reisolated and identified by sequencing, and no pathogens were isolated from symptomless control plants. To our knowledge, this is the first report of Ca. montana causing L. fischeri leaf spot. The disease poses a threat to the production and more control strategies are needed on management options to minimize losses.

Brachybotrys paridiformis Maxim. ex Oliv. (Boraginaceae) is a perennial medicinal plant and vegetable that is cultivated commercially in China. Anthracnose is a devastating disease of B. paridiformis , with annual production losses exceeding 33% based on our survey. In July 2021, anthracnose of B. paridiformis was observed on 2-year-old plants in Shenyang city, Northeast China, which is the most important region for B. paridiformis cultivation. Round or irregular-shaped black spots were exhibited on leaves, with the leaf edges most commonly infected. As the necrosis expanded, the leaves withered and dropped; young leaves were generally not infected (Fig. 1). More than 40% of the plants in a 21-ha sampling field were infected in 2021. Symptomatic leaves (n = 20) were collected and the diseased tissue was cut into small pieces, immersed in 1% NaOCl for 2 min, rinsed three times with sterile water, and placed on acidified potato dextrose agar (PDA) in Petri dishes. After a 3-day incubation in darkness at 25 °C, 18 suspected single-pure morphologically identical Colletotrichum isolates were obtained and sequenced. Isolate SQZ9 was randomly selected and identified. Colonies on PDA were initially white, but gradually became pale brownish with a reverse side that was pale yellowish to pinkish. Aerial mycelia were grayish-white, dense, and cottony, with microsclerotia detected on some aging mycelia. The detected single-celled conidia (11.65-17.25 × 4.25-6.15 µm; n = 50) were fusiform to cylindrical with obtuse to slightly rounded ends. Appressoria were ovoid to clavate and medium brown. Setae were not observed. The morphological characteristics were similar to those of Colletotrichum spp. (Prihastuti et al. 2009; Weir et al. 2012). Initial BLAST searches of the GenBank database revealed the SQZ9 rDNA internal transcribed spacer region (OP389109, 566 bp), glyceraldehyde-3-phosphate dehydrogenase (OP407730, 260 bp), chitin synthase (OP407731, 301 bp), calmodulin (OP407732, 712 bp), actin (OP407733, 282 bp), glutamine synthetase (OP407734, 909 bp), β-tublin (OP407735, 498 bp), and superoxide dismutase (OP407736, 396 bp) sequences were respectively 99%-100% similar to the C. siamense type strain JX010278, JX010019, JX009709, GQ856775, GQ856730, JX010100, JX010410, and JX010332 sequences (Carbone & Kohn 1999; Moriwaki & Tsukiboshi 2009; Stephenson et al. 1997). The SQZ9 identity was confirmed by constructing a phylogenetic tree combining all loci, which grouped the isolate and the C. siamense type strain in the same clade (Fig. 2). For pathogenicity tests, 15 healthy 2-year-old plants (3 plants per pot) were spray-inoculated with SQZ9 conidial suspension (1 × 105 conidia/mL) at 2 mL per plant. Same number of plants sprayed with water were used as control. This experiment was repeated twice. All plants were covered with clear plastic bags for 72 h to maintain high humidity and then placed in a greenhouse (29 °C, natural light, and 85% relative humidity). After six days, the inoculated leaves exhibited symptoms that were similar to those observed in the field, but the controls were symptomless. The same fungus was recovered from inoculated symptomatic leaves, and its identity was confirmed by sequencing and a phylogenetic analysis. This is the first report of C. siamense causing anthracnose on B. paridiformis in China. Future studies should assess the effectiveness of chemical and biological control measures for managing this disease.

The immense impacts of coal-fired power plant plumes on the atmospheric environment have caused great concern linked to climate and health issues. However, studies on the field observations of aerial plumes are relatively limited, mainly due to the lack of suitable plume observation tools and techniques. In this study, we use a multicopter unmanned aerial vehicle (UAV) sounding technique to study the influences of the aerial plumes of the world's fourth-largest coal-fired power plant on the atmospheric physical/chemical conditions and air quality. A set of species, including 106 volatile organic compounds (VOCs), CO, CO 2 , CH 4 , PM 2.5 , and O 3 , and meteorological variables of temperature (T), specific humidity (SH), and wind data, are collected by the UAV sounding technique. The results reveal that the large-scale plumes of the coal-fired power plant cause local temperature inversion and humidity changes, and even affect the dispersion of pollutants below. The chemical compositions of coal-fired power plant plumes are significantly different from those of another ubiquitous vehicular source. High fractions of ethane, ethene, and benzene and low fractions of n-butane and isopentane found in plumes could serve as the key features to help distinguish the influences of coal-fired power plant plumes from other pollution sources in a particular area. By taking the ratios of pollutants (e.g., PM 2.5 , CO, CH 4 , and VOCs) to CO 2 in plumes and the CO 2 emission amounts of the power plant into calculation, we enable the easy quantification of the specific pollutant emissions released from power plant plumes to the atmosphere. In summary, observation by using drone soundings dissecting the aerial plumes provides a new methodology that allows aerial plumes to be readily detected and characterized. Furthermore, the influences of the plumes on the atmospheric physical/chemical conditions and air quality can be assessed rather straightforwardly, which was not easily achievable in the past., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

To conduct a study that examined the molecular epidemiology and pathogenesis of Salmonella Senftenberg isolates associated with an outbreak of foodborne disease in Guizhou Province and to provide a reference basis for the traceability of foodborne salmonellosis outbreaks and clinical diagnosis and treatment in the province. Fourteen strains of suspected Salmonella isolated from patient stool and food samples were used for pathogenic identification and serotyping by biochemical and mass spectrometry methods. Fourteen types of antibiotics were tested for drug sensitivity by the microbroth dilution method, and molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). After the sequencing data were spliced by SPAdes, the gene protein sequences were compared with the Comprehensive Antibiotic Research Database and Virulence Factor Database, drug resistance and virulence genes were predicted, and whole genome multilocus sequence typing (wgMLST) was performed. The results were compared with those for Salmonella strains of the same serotype from the past 5 years in China detailed on the TraNet website. All 14 strains were identified as Salmonella Senftenberg (with the antigenic formula 1,3,19:g,s,t:-), and in the PFGE cluster tree, the strains were divided into two band types, with a similarity of 88.9%. The 14 strains were sensitive to the 14 antibiotics. WGS analysis showed that the 14 strains carried the same drug resistance and virulence genes and that all strains carried 3 aminoglycoside and lipopeptide drug resistance genes, including 114 virulence genes. The wgMLST results showed that the strains were distributed on the same small branch as those obtained from previous outbreaks of infection in Tianjin and Jilin. Salmonella Senftenberg, which caused the outbreak, carries a variety of virulence genes, which suggests that the strain is highly pathogenic. These pathogenic bacteria may be associated with the Salmonella strain in Tianjin, Jilin, and other places and have caused foodborne disease outbreaks as a result of imported contamination.

Background: Lamb-Shaffer syndrome (LAMSHF, MIM 616,803) is a rare neurodevelopmental disorder due to haploinsufficiency of SOX5. Furthermore, studies about the clinical features of LAMSHF patients with same allele of c.1477C > T (p. R493*) are very limited., Case Presentation: We analyzed the phenotypes of one of our cases and two previously reported cases with c.1477C > T (p. R493*), and reviewed the correlating literature. A de novo heterozygous variation c.1477C > T (p. R493*) in SOX5 was identified in a 4 years and 2 months old boy with global development delay by trio-based whole exome sequencing. We compared our case and previously 2 cases reported with recurrent variation, the overlapping clinical features are global developmental delay or intellectual disability, language delay and scoliosis, but their other clinical characteristics are different., Conclusions: This study suggests that the clinical features of LAMSHF patients with recurrent variations in the SOX5 gene are different. It is suggested that the LAMSHF-related SOX5 gene should be screened and included as one of the candidate genes for neurodevelopmental disorders of unknown etiology., (© 2023. The Author(s).)

Tribulus terrestris L. is an annual herbaceous medicinal plant of Zygophyllaceae, which is cultivated commercially in China. Subrotund or irregular gray, sunken, necrotic spots ranging from 2 to 9 mm were observed on diseased leaves of T. terrestris landrace in Fushun County, Liaoning Province of northeast China in July 2021, with more than 32% of the plants being infected in a 18-ha field. The symptoms first appeared on older leaves and gradually spread to younger leaves. The lesions developed a white center gradually and became perforated; multiple lesions could coalesce (Fig. 1). Ten symptomatic leaves were collected and the diseased tissues were cut into small pieces, immersed in 1% NaOCl for 2 min, rinsed three times with sterile water, and placed on acidified potato dextrose agar (PDA) in Petri dishes at 25°C in darkness. Fifteen suspected Colletotrichum single-spore fungal isolates (JL1 to JL15) with consistent morphological characteristics were obtained, and isolate JL6 was selected for identification and pathogenicity testing. Colonies on PDA were flat with an entire margin, dense and white at first, then became dark gray with numerous black microsclerotia and formed a concentric circular pattern with aging. Conidia were single-celled, sickle-curved with a tapered tip and truncate base, ranging from 16.46 to 20.26 μm in length and 2.81 to 3.96 μm in width (n=100). Setae were dark brown, septate, straight with a slightly acute tip, 75.45 to 135.63×3.19 to 4.95 μm in size. Appressoria were dark brown, round or irregular, mostly in groups. All characteristics were consistent with the descriptions of C. truncatum (Damm et al. 2009). Further confirmation of the identification was determined according to methods described previously (Damm et al. 2009). The rDNA internal transcribed spacer region (OP364400, 585 bp), and actin (OP380867, 290 bp), beta-tubulin (OP380868, 498 bp), chitin synthase 1 (OP380869, 277 bp), glyceraldehyde-3-phosphate dehydrogenase (OP380870, 280 bp), and histone (OP380871, 411 bp) genes were amplified by PCR and sequenced (Carbone and Kohn 1999; Glass and& Donaldson 1995; Guerber et al. 2003; O'Donnell and Cigelnik 1997). BLAST results showed 98-100% similarity at 85-97% coverage compared to the corresponding sequences of the type strain CBS 151.35 (GU227862, GU227960, GU228156, GU228352, GU228254, and GU228058). Phylogenetic analysis combining all loci revealed that the isolate JL6 and the type strains of C. truncatum clustered in one group (Fig. 2). One-year-old healthy seedlings of T. terrestris (cultivar: landrace) were used for pathogenicity test. Suspension (1×10 5 conidia/mL) of isolate JL6 was sprayed on ten seedlings, and ten seedlings sprayed with sterilized distilled water were used as the control. Three replicates were performed on each treatment. All plants were kept at 28±1°C (12 h photoperiod), and were evaluated after 7 days. The inoculated plants showed lesions on the leaf surface, similar to those in the field, and the control remained symptomless. The pathogen was successfully reisolated and identified using the methods mentioned above. To our knowledge, this is the first report of C. truncatum causing anthracnose on T. terrestris , which will provide valuable information for designing strategies to manage anthracnose on T. terrestris .

Endophytes and their elicitors can all be utilized in regulating crop biochemical qualities. However, living endophytes and their derived elicitors are always applied separately; little is known about the similarities and differences of their effects. To increase the efficiency of this system when applied in practice, the present work profiled simultaneously the metabolomes in grape cells exposed to endophytic fungi (EF) and their corresponding fungal extracts (CFE). As expected, grape cells exposed separately to different fungi, or to different fungi derived extracts, each exhibited different modifications of metabolite patterns. The metabolic profiles of certain EF- and CFE-exposed grape cells were also differently influenced to certain degrees, owing to the presence of differentially responding metabolites (DRMs). However, the detected majority proportions of coordinately responding metabolites (CRMs) in both the EF- and the CFE-exposed grape cells, as well as the significantly influenced metabolites (SIMs) which are specific to certain fungal strains, clearly indicate coordinative changes in metabolites in grape cells exposed to EF and CFEs. The coordinative changes in metabolites in EF- and CFE-treated grape cells appeared to be fungal strain-dependent. Notably, several of those fungal strain-specific CRMs and DRMs are metabolites and belong to amino acids, lipids, organic acids, phenolic acids, flavonoids, and others, which are major contributors to the biochemistry and sensory qualities of grapes and wines. This research clarifies the detailed responses of metabolites in grape cells exposed to EF and CFEs. It also demonstrates how endophytes can be selectively used in the form of extracts to produce functions as CRMs of the living fungus with increased eco-safety, or separately applied to the living microbes or elicitors to emphasize those effects related to their specifically initiated SIMs and DRMs.

East Asian continental outflows containing with pollutants may deteriorate air quality in the downwind region via long-range transport (LRT). In particular, cold fronts with high wind speeds generally promote the LRT of air pollutants to further downwind areas, including Taiwan. To gain an insightful understanding of the characteristics and vertical homogeneity of trace gases in East Asian continental outflows, as well as their relation with atmospheric meteorological conditions, whole air samples were collected above a cape at the northern tip of the island of Taiwan during frontal passages. Aerial samples were collected at multiple altitudes from the surface to a maximum height of 700 m with a multicopter sounding platform carrying a robotic whole air sampling device. Simultaneously, aerial meteorological variables of temperature and wind vector from near the surface to a maximum height of 1000 m were also measured during the whole air sampling periods. An array of 106 volatile organic compounds (VOCs) as well as CO, CO 2 , and CH 4 were analyzed to characterize the air composition and vertical homogeneity of trace gases. The results revealed rather homogeneous vertical distributions of most VOCs, CO, CO 2 , and CH 4 in the frontal passages, indicating well-mixed conditions of trace gases in the East Asian continental outflows. The strong wind shear and minimal temperature inversion associated with the frontal passage likely induced turbulence and increased vertical mixing. Furthermore, higher levels of species characteristic of the East Asian continent were observed from the surface up to hundreds of meters above the cape, revealing a strong inflow of polluted air masses from the East Asian continent brought by cold frontal passages., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

IgG4-related disease (IgG4-RD) is an immune-mediated condition associated with chronic fibroinflammatory lesions that can affect nearly any organ. IgG4-related hepatobiliary and pancreatic diseases are IgG4-RD involving the hepatobiliary and pancreatic system, which is characterized with elevated serum IgG4 concentrations, large numbers of IgG4 positive lymphoplasma cells infiltration in affected organs, storiform fibrosis, and imaging changes of organ morphology. Due to the lack of reliable biomarkers, histopathology is still an important basis for diagnosis. The pathogenesis of IgG4-related hepatobiliary and pancreatic diseases has not been clarified. This review focuses on the recent advances in intestinal microecology-immunology, host genetics-immunity and recurrence monitoring of IgG4-related hepatobiliary and pancreatic diseases.

To reveal the formation mechanism of fungal community and diversity during the production of Shaoxing Huangjiu, we examined fungal communities in the samples of Linfanjiumu, Maiqu and fermentation mash based on Illumina MiSeq PE300 high-throughput sequencing platform. A total of 136000, 215283, 166150, and 143624 sequences were obtained from the samples of Linfanjiumu, Maiqu, initial mash and mature mash, respectively. After clustering, 32, 133, 107 and 84 OUT (operational taxonomic units) were obtained, respectively. The diversity and richness of fungi were in order of Maiqu > initial mash > mature mash > Linfanjiumu. At the level of phylum, Ascomycota were dominant in all samples. At genus level, Saccharomyces was dominant in Linfanjiumu, Aspergillus was dominant in Maiqu, and Saccharomyces and Aspergillus were the dominant fungi in the initial and mature mash. With the extension of the fermentation time, the proportion of Saccharomyces gradually increased in the mash, while other fungal groups including Aspergillus showed a decreasing trend. According to the results of PCoA analysis and similarity cluster analysis, the structure of fungi community in Linfanjiumu, initial mash and mature mash was much similar, while the fungal resources in Maiqu were quite different from other samples. The analysis of fungal community characteristics in the initial mash showed that the Linfanjiumu and Maiqu affected fungal diversity in Shaoxing Huangjiu. The dominant species of saccharification and fermentation starter (Linfanjiumu and Maiqu) played a leading role in driving community assembly of fermentation fungi.

Cardiac remodeling consisted of ventricular hypertrophy and interstitial fibrosis is the pathological process of many heart diseases. Fibroblasts as one of the major cells in the myocardium regulate the balance of the generation and degeneration of collagen, and these cells transform toward myofibroblasts in pathological state, contributing to the remodeling of the heart. Peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator-1α (PGC-1α) is vital to the function of mitochondria, which contributes to the energy production and reactive oxidative species (ROS)-scavenging activity in the heart. In this study, we found that fibroblast-specific PGC-1α KO induced cardiac remodeling especially fibrosis, and Angiotensin II (AngII) aggravated cardiac fibrosis, accompanied with a high level of oxidative stress response and inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Pan, Ding, Ruan and Gao.)

Backgrounds: Chronic urticaria is a common disorder of the skin, characterised by recurrent skin wheals and angioedema. Recent reports have shown that altered diversity and composition of the gut microbiota may lead to imbalances in immune regulation, a causal factor in the occurrence of chronic urticaria., Objective: This study aimed to evaluate the efficacy of the Yimingjia ® probiotic formula in the adjuvant treatment of chronic urticaria in children., Methods: We enrolled 206 children with confirmed diagnoses of chronic urticaria and randomly assigned them to the treatment (n = 104) or placebo group (n = 102). The children in each group were treated with desloratadine dry suspension, and those in the treatment group also received Yimingjia ® . Clinical efficacy was evaluated at 1, 2 and 4 weeks., Results: Clinical symptom scores did not differ significantly at weeks 1 and 2 (p > 0.05), but at 4 weeks, wheal size and attack frequency were significantly reduced in the treatment group (p = 0.049 and 0.03, respectively). The overall response rate (significant improvement + complete response) significantly differed between the treatment (80.8%) and placebo groups (62.5%) (χ 2  = 4.20, p = 0.04)., Conclusion: Adjunct therapy with Yimingjia ® was safe and effective at 4 weeks in the treatment of chronic urticaria in children. The study was registered under trial number NCT03328897.

Dehydrins (DHNs) play an important role in abiotic stress tolerance in a large number of plants, but very little is known about the function of DHNs in pepper plants. Here, we isolated a Y 1 SK 2 -type DHN gene " CaDHN3 " from pepper. To authenticate the function of CaDHN3 in salt and drought stresses, it was overexpressed in Arabidopsis and silenced in pepper through virus-induced gene silencing (VIGS). Sub-cellular localization showed that CaDHN3 was located in the nucleus and cell membrane. It was found that CaDHN3 -overexpressed (OE) in Arabidopsis plants showed salt and drought tolerance phenotypic characteristics, i.e., increased the initial rooting length and germination rate, enhanced chlorophyll content, lowered the relative electrolyte leakage (REL) and malondialdehyde (MDA) content than the wild-type (WT) plants. Moreover, a substantial increase in the activities of antioxidant enzymes; including the superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and lower hydrogen peroxide (H 2 O 2 ) contents and higher O 2 •- contents in the transgenic Arabidopsis plants. Silencing of CaDHN3 in pepper decreased the salt- and drought-stress tolerance, through a higher REL and MDA content, and there was more accumulation of reactive oxygen species (ROS) in the CaDHN3 -silenced pepper plants than the control plants. Based on the yeast two-hybrid (Y2H) screening and Bimolecular Fluorescence Complementation (BiFC) results, we found that CaDHN3 interacts with CaHIRD11 protein in the plasma membrane. Correspondingly, the expressions of four osmotic-related genes were significantly up-regulated in the CaDHN3 -overexpressed lines. In brief, our results manifested that CaDHN3 may play an important role in regulating the relative osmotic stress responses in plants through the ROS signaling pathway. The results of this study will provide a basis for further analyses of the function of DHN genes in pepper.

Aging-associated chronic inflammation is a key contributing factor to a cluster of chronic metabolic disorders, such as cardiovascular disease, obesity, and type 2 diabetes. Immune cells particularly T cells accumulate in adipose tissue with advancing age, and there exists a cross talk between T cell and preadipocyte, contributing to age-related adipose tissue remodeling. Here, we compared the difference in morphology and function of adipose tissue between young (3-month-old) and old (18-month-old) mice and showed the phenomenon of brown adipose tissue (BAT) "whitening" in old mice. Flow cytometry analysis suggested an increased proportion of T cells in BAT of old mice comparing with the young and exhibited senescent characteristics. We take advantage of coculture system to demonstrate directly that senescent T cells inhibited brown adipocyte differentiation of preadipocytes in adipose tissue. Mechanistically, both in vitro and in vivo studies suggested that senescent T cells produced and released a higher level of IFN-γ, which plays a critical role in inhibition of preadipocyte-to-brown adipocyte differentiation. Taken together, the data indicate that senescent T cell-derived IFN-γ is a key regulator in brown adipocyte differentiation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pan, Yao, Yang, Ge, Zhang, Gao, Ruan and Wu.)

Objectives: Renal risk score (RRS) and chronicity score (CS) are both newly proposed tools to predict end stage renal disease (ESRD) which could be applicable in antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis patients. Their predictive value has not been fully studied and compared., Methods: 252 patients with newly biopsy-proven ANCA-associated renal vasculitis were retrospectively studied at the Department of Nephrology, Ruijin Hospital, China. Patients were evaluated with RRS and CS for clinical factors, pathological lesions and outcome. Their predictive value of renal survival was also compared., Results: The median RRS score point at diagnosis was 6 (interquartile range [IQR] 0-9) and CS score point was 4 (IQR 3-7). In accordance with severity of RRS category and CS grade, percentage of hypertensive patients, dialysis dependency, and level of proteinuria increased accordingly. Significant differences were found regarding dialysis dependency within RRS and CS groups (p<0.001 and p<0.01 respectively). The addition of RRS or CS scoring scheme to the base model of dialysis dependency significantly improved discrimination. The C statistic, integrated discrimination improvement and net reclassification improvement were significantly increased by adding either RRS/CS or both. Furthermore, RRS had better ROC., Conclusions: Among ANCA associated renal vasculitis patients, RRS and CS achieved similar discrimination, but the discrimination of RRS was superior.

Aims: Aging is a risk factor for cardiovascular diseases and adaptive immunity has been implicated in angiotensin (Ang) II-induced target organ dysfunction. Herein, we sought to determine the role of T-cell senescence in Ang II-induced target organ impairment and to explore the underlying mechanisms., Methods and Results: Flow cytometric analysis revealed that T cell derived from aged mice exhibited immunosenescence. Adoptive transfer of aged T cells to immunodeficient RAG1 KO mice accelerates Ang II-induced cardiovascular and renal fibrosis compared with young T-cell transfer. Aged T cells also promote inflammatory factor expression and superoxide production in these target organs. In vivo and in vitro studies revealed that Ang II promotes interferon-gamma (IFN-γ) production in the aged T cells comparing to young T cells. Importantly, transfer of senescent T cell that IFN-γ KO mitigates the impairment. Aged T-cell-conditioned medium stimulates inflammatory factor expression and oxidative stress in Ang II-treated renal epithelial cells compared with young T cells, and these effects of aged T-cell-conditioned medium are blunted after IFN-γ-neutralizing antibody pre-treatment., Conclusion: These results provide a significant insight into the contribution of senescent T cells to Ang II-induced cardiovascular dysfunction and provide an attractive possibility that targeting T cell specifically might be a potential strategy to treat elderly hypertensive patients with end-organ dysfunction., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.

Objective: To describe the basic characteristics of clusters of coronavirus diseases 2019 (COVID-19) cases in Ningbo, Zhejiang province, and evaluate the generation time (Tg) and basic reproduction number ( R (0)) of COVID-19. Methods: The basic information and onset times of the clusters of COVID-19 cases in Ningbo were investigated, the inter-generational interval of the cases were fitted by using gamma distribution, and the R (0) was calculated based on the SEIR model. Results: In the 15 clusters of COVID-19 cases, a total of 52 confirmed cases, 5 cases of nucleic acid-positive asymptomatic cases. The cases occurred from January 23 to February 4, the cases were mainly women. The incubation period was (6.11±3.38) days, and the median was 5 days. The Tg was (6.93±3.70) days. There were no significant differences in Tg between age group<60 years and age group 60 years and above, and between men and women ( P =0.551). According to the Tg calculated in this paper, the R (0) of COVID-19 in Ningbo was 3.06 (95 %CI : 2.64- 3.51); according to the reported case transmission interval of 7.5 days in the literature, the R (0) was 3.32 (95 %CI : 2.51-9.38). Conclusion: There is no age and gender specific differences in the Tg of clusters of COVID-19 cases in Ningbo, and COVID-19 has high infectivity and spreading power in early phase.

CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). In this study, we aimed to explore the anticancer effects of CUDC-907 on human breast cancer cells. Our results showed that CUDC-907 effectively inhibited breast cancer cell proliferation. Flow cytometry analysis revealed that CUDC-907 induced cell cycle arrest and apoptosis in breast cancer cells. The combined treatment of CUDC-907 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resulted in a marked increase in apoptosis and cleavage of caspase-8, -9 and poly (ADP-ribose) polymerase (PARP) in breast cancer cells. CUDC-907 enhanced expressions of death receptor 5 (DR5), reduced the levels of anti-apoptotic molecules XIAP, Bcl-2 and Bcl-xL. Knockdown of DR5 abrogated apoptosis induced by the combination of CUDC-907 and TRAIL in breast cancer cells. CUDC-907 increased the phosphorylation of JNK and p38 MAPK. JNK inhibitor pretreatment attenuated CUDC-907-induced upregulation of DR5. In summary, CUDC-907 shows potent cytotoxicity against breast cancer cells and facilitates TRAIL-mediated apoptosis through DR5 upregulation. The combination of CUDC-907 and TRAIL may be a promising therapeutic approach in the treatment of breast cancer.

Endophytic fungi produce many novel bioactive metabolites that are directly used as drugs or that function as the precursor structures of other chemicals. The metabolic shaping of endophytes on grape cells was reported previously. However, there are no reports on the interactions and metabolic impact of endophyte symbiosis on in vitro vine leaves, which may be examined under well-controlled conditions that are more representative of the natural situation of endophytes within grapevines. The present study used an in vitro leaf method to establish endophyte symbiosis of grapevines and analyze the effects on the metabolic profiles of grape leaves from two different cultivars, 'Rose honey' (RH) and 'Cabernet sauvignon' (CS). The effects of endophytic fungi on the metabolic profiles of grape leaves exhibited host selectivity and fungal strain specificity. Most of the endophytic fungal strains introduced novel metabolites into the two varieties of grape leaves according to the contents of the detected metabolites and composition of metabolites. Strains RH49 and MDR36, with high or moderate symbiosis rates, triggered an increased response in terms of the detected metabolites, and the strains MDR1 and MDR33 suppressed the detected metabolites in CS and RH leaves despite having strong or moderate symbiosis ability. However, the strain RH12 significantly induced the production of novel metabolites in RH leaves due to its high symbiosis ability and suppression of metabolites in CS leaves., Competing Interests: The authors have declared that no competing interests exist.

The unique maneuverability, ease of deployment, simplicity in logistics, and relatively low costs of multicopters render them effective vehicles for low atmospheric research. While many efforts have contributed to the fundamental success of atmospheric applications of multicopters in the past, several challenges remain, including limited measurable variables, possible response-delay in real-time observations, insufficient measurement accuracy, endurance of harsh conditions and tolerance towards interferences. To address these challenges and further fortify the applicability in diversified research disciplines, this study developed an optimized multicopter UAV sounding technique (MUST). The MUST serves as an integrated platform by combining self-developed algorithms, optimized working environments for sensors/monitors, and retrofitted sampling devices to probe a comprehensive set of atmospheric variables. These variables of interest include meteorological parameters (temperature, relative humidity, pressure, wind direction and speed), the chemical composition (speciated VOCs, CO, CO 2 , CH 4 , CO 2 isotopologues, O 3 , PM2.5, and black carbon), and the radiation flux, as well as visible and thermal images. The aim of this study is to achieve the following objectives: 1. to easily probe a comprehensive set of near-surface atmospheric variables; 2. to improve data quality by correcting for sensors' delay in real-time observations and minimizing environmental interferences; and 3. to enhance the versatility and applicability of aerial measurements by incorporating necessary hardware and software. Field launching cases from the surface to a maximum height of 1000 m were conducted to validate the robustness of the integrated MUST platform with sufficient speed, accuracy and resolution for the target variables., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Non-small cell lung cancer (NSCLC) is a major source of cancer mortality. Long non-coding RNA DSCAM-AS1 has been certified to be involved in the pathogenesis of NSCLC. This study aimed to further investigate the potential mechanism of DSCAM-AS1 in NSCLC progression. The expressions of DSCAM-AS1, miR-577, and high mobility group box 1 (HMGB1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry assay was conducted to monitor cell apoptosis. Cell migration and invasion were measured by transwell assay. Wnt/β-catenin pathway-related factors were detected by western blot assay. The relationship between DSCAM-AS1, miR-577, and HMGB1 was validated by bioinformatics analysis and dual-luciferase reporter assay. The xenograft mouse model was established to analyze tumor growth in vivo. DSCAM-AS1 and HMGB1 were upregulated, while miR-577 was downregulated in NSCLC tissues and cells. DSCAM-AS1 promoted cell proliferation, migration and invasion, and restrained cell apoptosis in NSCLC cells. Overexpression of HMGB1 reversed the effects of DSCAM-AS1 depletion on the progression of NSCLC. DSCAM-AS1 modulated HMGB1 expression by sponging miR-577. DSCAM-AS1 regulated the Wnt/β-catenin pathway by regulating miR-577 and HMGB1. DSCAM-AS1 knockdown blocked the tumor growth in vivo. In conclusion, DSCAM-AS1 facilitated NSCLC progression by regulating the HMGB1-mediated Wnt/β-catenin pathway, providing a promising therapeutic target for NSCLC.

Based on the premise of sustainable development of the environment, how to achieve the balance of energy utilization, economic development, and sustainable management of the environment is becoming increasingly important in the process of stable economic development. This paper analyzes the concept of environmental Kuznets curve, taking 35 European countries as the research objects, first discusses the trend of energy utilization efficiency from 1990 to 2013, and then analyzes the relationship between energy efficiency and economic development. Empirical results show that labor has a significant negative impact on energy efficiency and the increase in labor input will reduce energy efficiency. If the added value of national manufacturing accounts for a higher percentage in GDP, it will have a negative impact on the effectiveness of energy utilization. In addition, when the national price level is high, price fluctuation will increase the price of energy utilization, or the cost of energy input in economic activities, which will further reduce the country's energy efficiency performance. Lastly, the empirical study also found that energy efficiency and economic development showed a quadratic U-shaped relationship, indicating that the long-term energy efficiency of the country will first decline and then rise during economic activities.

Anthocyanins contribute greatly to the organoleptic and biochemical properties of grapes and wines. Although there are broadly documented factors involved in grape anthocyanin synthesis, the present work focused on fungal endophytes and their possible role in grape coloration. Our results showed that exposure to endophytic fungi within a dual culture system differentially affected total anthocyanin concentrations and PAL activities in grape cells. Grape cells dual cultured with fungal strains XH-2, R2-21 and B2-17 showed significant differences of their anthocyanin concentrations were subjected to further analysis of their anthocyanidin compositions. Compared to the no-fungus controls, grape cells exposed to fungal strains XH-2 and R2-21 exhibited quantitative promotion of their total anthocyanidin concentrations by 74% and 28%, respectively, whereas treatment with the fungus B2-17 reduced the anthocyanidin content by 19%. A total of 14 species of anthocyanidins were detected from the grape cells in these experiments. Most interestingly, exposure to any of these fungal strains differentially modified the compositional patterns of grape cellular anthocyanidins. The obvious upregulation of the transcription of VvMYB in grape cells treated with fungal strains XH-2 and R2-21 implies that the increased anthocyanin levels in these grape cells may be due to the activated transcriptional factors. In addition, the exposure of grape cells to extracts of these fungi initiated similar responses of anthocyanin contents and PAL activities to exposure to the living fungi and appeared obvious dosage effects. The influence of fungal endophytes on the coloration of grape berries was also examined in this study., Competing Interests: Declaration of competing interest I would like to declare on behalf of my co-authors that the submission of the manuscript entitled “Exposure to endophytic fungi quantitatively and compositionally alters anthocyanins in grape cells”, has no conflict of interest exists, and manuscript is approved by all authors for publication. The work described was original research that has not been published previously, and also not under consideration for publication elsewhere, in whole or in part., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: No study so far has paid attention to strabismus-related spinal imbalance. This study aimed to determine the epidemiology of thoracic scoliosis in children and adolescents with strabismus and investigate the association of two diseases., Methods and Design: A cross-sectional study. Study group consists of 1935 consecutive candidates for strabismus surgery (4-18 years); Control group consists of the age- and sex-matched patients with respiratory diseases. All subjects underwent a screening program based on chest plain radiographs using the Cobb method. Their demographic information, clinical variables and results of Cobb angle were recorded and analyzed., Results: A significantly higher prevalence of thoracic scoliosis (289/1935, 14.94% versus 58/1935, 3.00%) was found in study group compared with control group. Among strabismic patients, the coronal thoracic scoliosis curve mainly distributed in right and in main thoracic (198/289) and in the curves 10°-19° (224/289); Age range 7-9 years (103/1935), female (179/1935) and concomitant exotropia patients (159/851) were more likely to have thoracic scoliosis. According to the logistic regression, thoracic scoliosis had no significant association with age, BMI, duration of illness and onset age (p > 0.05). However, gender, BCVA, type of strabismus and degree of strabismus showed a significant relationship with the prevalence of thoracic scoliosis (p < 0.05)., Conclusions: With a pooled prevalence of 14.94%, strabismus patients showed a great higher risk of developing thoracic scoliosis. Screening for scoliosis in strabismus patients can be helpful to discover a high prevalence of potential coronal scoliosis. More attention should be paid to ophthalmological problems in patients with scoliosis. These slides can be retrieved under Electronic Supplementary Material.

Objectives: There is currently no consensus on the prognostic significance of the histological subtype of nasopharyngeal carcinoma (NPC). The aim of the current study was to evaluate the impact of histological subtype on survival in NPC patients based on the Surveillance, Epidemiology, and End Results (SEER) Program., Methods: Patients with NPC were identified within the SEER database (2004-2015). The effects of histological subtype on cause-specific survival (CSS) in NPC patients were evaluated using univariate and multivariate Cox regression analyses. Subgroup analysis according to histological subtype in NPC patients was carried out by 1:1 propensity score matching (PSM)., Results: A total of 4085 NPC patients were selected from the SEER database, including 1929 with keratinizing squamous cell carcinoma (KSCC), 2203 with nonkeratinizing carcinoma (NKC), and 53 with basaloid squamous cell carcinoma (BSCC). The 3-year and 5-year CSS rates were 61.76% and 55.07% for KSCC patients, 79.57% and 72.09% for NKC patients, and 77.55% and 74.03% for BSCC patients, respectively. Multivariate analysis identified sex, age, marital status, race, T stage, N stage, M stage, radiotherapy, chemotherapy, and histological subtype as significant prognostic factors for CSS in NPC patients. KSCC was found to be associated with worse CSS than NKC on Kaplan-Meier analysis and subgroup analysis after 1:1 PSM., Conclusions: Histological subtype determines the long-term survival outcomes of patients with NPC. Moreover, the NKC subtype has the best prognosis, while the KSCC subtype has the worst prognosis., Level of Evidence: NA Laryngoscope, 130:E83-E88, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

In this work, MoS₂ nanosheets (NSs) are applied as a novel anode to deliver a high-performance supercapacitor (SC). A MoS₂ NSs anode with a special honeycomb-shaped structure, is synthesized using a hydrothermal method, and subsequently applied in conjunction with an electrodeposited Co(OH)₂ NSs cathode to create a new cost-effective aqueous hybrid SC cell. The as-fabricated Co(OH)₂//MoS₂ hybrid SC exhibits a number of attractive characteristics, including: (1) a stable operation voltage window of 1.5 V; (2) remarkable cycling stability with a retention ratio of 92.3% after 4000 cycles; (3) an energy density of 24.0 Wh kg -1 at a current density of 0.5 mA cm -2 and a high power density of 1932.0 W kg -1 at a current density of 2.5 mA cm -2 . The experimental results evidence that MoS₂ is a promising candidate for the development of SC anodes.

The development of opioid-induced analgesic tolerance is a clinical challenge in long-term use for managing chronic pain. The mechanisms of morphine tolerance are poorly understood. Mitochondria-derived reactive oxygen species (ROS) is a crucial signal inducing analgesic tolerance and pain. Chronic administration of morphine leads to robust ROS production and accumulation of damaged mitochondria, which are immediately removed by mitophagy. Here, we show that morphine inhibits mitochondria damage-induced accumulation of PTEN-induced putative kinase 1 (PINK1) in neurons. It interrupts the recruitment of Parkin to the impaired mitochondria and inhibits the ubiquitination of mitochondrial proteins catalyzed by Parkin. Consequently, morphine suppresses the recognition of autophagosomes to the damaged mitochondria mediated by LC3 and sequestosome-1 (SQSTM1/p62). Thus, morphine inhibits autophagy flux and leads to the accumulation of SQSTM1/p62. Finally, the impaired mitochondria cannot be delivered to lysosomes for degradation and ultimately induces robust ROS production and morphine tolerance. Our findings suggest that the dysfunction of mitophagy is involved in morphine tolerance. The deficiency of PINK1/Parkin-mediated clearance of damaged mitochondria is crucial for the generation of excessive ROS and important to the development of analgesic tolerance. These findings suggest that the compounds capable of stabilizing PINK1 or restoring mitophagy may be utilized to prevent or reduce opioid tolerance during chronic pain management., (© The Author(s) (2019). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.)

Background: Chemotherapy resistance reduces the effectiveness of chemotherapeutic drugs greatly, resulting in treatment failure. Therefore, exploring chemoresistance-related genes and the corresponding mechanism is extremely important. The central role of CD44v6 in colorectal cancer has been previously reported. However, the effects of CD44v6 gene knockdown on the chemosensitivity of colorectal cancer cells are not conclusive., Material and Methods: A stable CD44v6 knockdown cell model in HT29 cells (HT29-KD) was established via lentiviral transduction. A quantitative real-time polymerase chain reaction (PCR) was carried out to confirm the knockdown efficiency. The chemosensitivity of cells to 5-fluorouracil (5-FU) was determined by a cell counting kit (CCK)-8 assay. Cell apoptosis and the cell cycle were assessed by flow cytometry., Results: The CD44v6 knockdown cell model was successfully constructed by using lentiviral transduction. Upon treatment with 5-FU, the inhibitory rate for cell activity of HT29-KD cells was significantly higher than that of the control group (HT29-NC). CD44v6 gene knockdown did not significantly affect HT-29 cell proliferation, according to the CCK-8 assay and cell cycle analysis. The cell apoptosis assay revealed that CD44v6 gene knockdown promoted HT-29 cell apoptosis. Without 5-FU treatment, there was no significant difference in terms of the relative expression level of the autophagy-related gene BECN1 between the two groups. However, with 5-FU treatment, the relative expression level of BECN1 in HT29-KD cells was much lower than that in HT29-NC cells., Conclusion: Our study confirms that CD44v6 gene knockdown can enhance chemosensitivity in HT29 cells by promoting apoptosis and inhibiting autophagy, thus affirming the effects of CD44v6 on the chemosensitivity of colorectal cancer., (© 2019 by the Association of Clinical Scientists, Inc.)

Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging-related vascular diseases. Here, we take advantage of single-cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging-induced loss of peroxisome proliferator-activated receptor-γ coactivator-1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery-induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background: Cervical sagittal imbalance compromises health-related quality of life and can lead to myriad incapacitating symptoms through compression of the spinal cord. Questions regarding which parameters play primary roles in the progression of cervical sagittal imbalance and which might be compensatory factors remain unanswered., Methods: This study enrolled 246 asymptomatic volunteers from July 2016 to June 2018. After demographic and radiologic parameters were measured, the data were analyzed using correlation coefficient test and multiple regression analysis. A predictive equation was assessed with variance analysis, residual analysis, collinearity analysis, and a paired t test., Results: Average values are as follows: orbital tilt, 64 ± 6°; orbital slope (OS), 15 ± 6°; C0-C2 lordosis (C0C2), 28 ± 8°; cervical lordosis (CL), 5 ± 11°; C2-C7 sagittal vertical axis (C2C7SVA), 15 ± 8 mm; T1 slope (TS), 17 ± 6°; thoracic inlet angle, 69 ± 8°; thoracic kyphosis, 34 ± 9°; lumbar lordosis, 50 ± 10°; sacral slope, 38 ± 7°; pelvic index, 48 ± 9°; sagittal vertical axis, 10 ± 19 mm. Correlations of C2C7SVA were observed with body mass index (BMI), OS, C0C2, CL, and TS. The validated predictive equation was: C2C7SVA = 0.38 × BMI - 0.73 × OS + 0.73 × C0C2 + 0.15 × CL + 0.18 × TS - 6.53., Conclusions: BMI, OS, C0C2, CL, and TS were primary influencers in the progression of cervical sagittal imbalance and established a predictive equation of asymptomatic population, which can provide clinical advice and remind surgeons of the primary influencers of reconstructive surgery for better prognoses., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: We sought to acquire the whole sagittal spine parameters and investigated the acceptable chin-brow vertical angle (CBVA) for neutral position radiography in an asymptomatic Chinese population., Methods: The parameters measured in 257 asymptomatic volunteers included CBVA, occipital slope, orbital tilt, occipital incidence, C0-C2 Cobb angle, C2-C7 Cobb angle, C1-C7 Cobb angle, C2-C7 sagittal vertical axis and absolute rotation angle, cervical tilt, cranial tilt, T1 slope, and thoracic kyphosis, and others. We used Pearson correlation analyses to find relationships between CBVA and other variables. The subjects were divided into 5 groups according to the CBVA percentile: group A, 0%-20% CBVA; group B, 20%-40% CBVA; group C, 40%-60% CBVA; group D, 60%-80% CBVA; and group E, 80%-100% CBVA. We used analysis of variance to analyze differences among the 5 groups., Results: Orbital tilt, Occipital incidence, C1-C7 Cobb angle, C2-C7 sagittal vertical axis, and cranial tilt all increased with increasing CBVA (P < 0.001). The occipital slope, C2-C7 Cobb angle, C2-C7 absolute rotation angle, cervical tilt, T1 slope, and thoracic kyphosis decreased with decreasing CBVA (P < 0.05). No correlations between other sagittal parameters and the CBVA were found. A slight deviation was found in groups B-D, with a greater deviation in groups A, C, and E., Conclusions: An acceptable range of -1.5° to 5.8° is recommended for the CBVA for cervical radiography in the neutral position. When spinal surgeons evaluate the cervical plane, the effects of the CBVA deviation on cervical curvature must be considered., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Pathological changes of the perivascular adipose tissue (PVAT) are directly associated with increased risk of age-related vascular diseases. MicroRNAs regulate adipocyte biological functions including adipogenic differentiation and white adipocyte browning. The present study aims to determine whether miR-146b-3p is involved in the regulation of perivascular adipocyte browning during aging., Methods: We utilized a cold-induced animal model to investigate the effect of aging on perivascular adipocyte browning. We also detected the miR-146b-3p expression in the PVAT of young or old mice after cold stimulus. We further investigated the role of miR-146b-3p in regulating perivascular adipocyte browning in vitro and in vivo via administrating miRNA mimics or inhibitors., Results: Old mice showed decrease of perivascular adipocyte browning and downregulation of miR-146b-3p expression in the PVAT after cold stimulus. Oil red O staining and qPCR indicated that aging perturbed preadipocyte to brown adipocyte differentiation, and expression of miR-146b-3p gradually increased during differentiation. MiR-146b-3p inhibitors blocked brown adipocyte differentiation in young preadipocytes, whereas miR-146b-3p mimics rescued the differentiation of the old preadipocytes. Finally, miR-146b-3p knocks down inhibited perivascular adipocyte browning in young mice after cold stimulus., Conclusion: Aging inhibits perivascular adipocyte browning, and loss of miR-146b-3p is a potential regulator for this process.

Purpose: The purpose of this study was to investigate finite element biomechanical properties of the novel transpedicular transdiscal (TPTD) screw fixation with interbody arthrodesis technique in lumbar spine., Methods: An L4-L5 finite element model was established and validated. Then, two fixation models, TPTD screw system and bilateral pedicle screw system (BPSS), were established on the validated L4-L5 finite element model. The inferior surface of the L5 vertebra was set immobilised, and moment of 7.5 Nm was applied on the L4 vertebra to test the range of motion (ROM) and stress at flexion, extension, lateral bending and axial rotation., Results: The intact model was validated for prediction accuracy by comparing two previously published studies. Both of TPTD and BPSS fixation models displayed decreased motion at L4-L5. The ROMs of six moments of flexion, extension, left lateral bending, right lateral bending, left axial rotation and right axial rotation in TPTD model were 1.92, 2.12, 1.10, 1.11, 0.90 and 0.87°, respectively; in BPSS model, they were 1.48, 0.42, 0.35, 0.38, 0.74 and 0.75°, respectively. The screws' peak stress of above six moments in TPTD model was 182.58, 272.75, 133.01, 137.36, 155.48 and 150.50 MPa, respectively; and in BPSS model, it was 103.16, 129.74, 120.28, 134.62, 180.84 and 169.76 MPa, respectively., Conclusion: Both BPSS and TPTD can provide stable biomechanical properties for lumbar spine. The decreased ROM of flexion, extension and lateral bending was slightly more in BPSS model than in TPTD model, but TPTD model had similar ROM of axial rotation with BPSS model. The screws' peak stress of TPTD screw focused on the L4-L5 intervertebral space region, and more caution should be put at this site for the fatigue breakage., The Translational Potential of This Article: Our finite element study provides the biomechanical properties of novel TPTD screw fixation, and promotes this novel transpedicular transdiscal screw fixation with interbody arthrodesis technique be used clinically.

Adipocytes play important roles in regulating cardiovascular health and disease. However, the molecular mechanism underlying the endocrine role of brown adipose tissue (BAT) in pathological cardiac remodeling remains unknown. Herein we show that adenosine A 2A receptor (A 2A R) knockout (A 2A RKO) causes interscapular BAT (iBAT) dysfunction, leading to accelerated cardiac remodeling in hypertension compared with wild-type (WT) mice. Surgical iBAT depletion induces dramatic cardiac remodeling in WT but not in A 2A RKO hypertensive mice. AMPK/PGC1α signaling-induced fibroblast growth factor 21 (FGF21) in brown adipocytes is required for A 2A R-mediated inhibition of hypertensive cardiac remodeling. Recombinant FGF21 administration improves cardiac remodeling in iBAT-depleted hypertensive mice. More importantly, brown adipocyte-specific A 2A RKO inhibits FGF21 production and accelerates cardiac damage in hypertension. Consistently, brown adipocyte-specific FGF21 knockout abolishes the effects of A 2A R agonism in attenuating hypertensive cardiac remodeling. Our findings reveal a distinctive endocrine role of BAT in hypertensive cardiac remodeling via activating A 2A R/FGF21 pathway., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: An increasing number of studies on spinal morphology in asymptomatic Asian and Western patients have been reported. Variation in spinal anatomy among patients is considered as the cause of wrong-level surgery in up to 40% of cases. The present study examined the rate of presence of 11 thoracic vertebrae and 6 lumbar vertebrae in 293 asymptomatic Chinese adult volunteers., Methods: From May 27, 2016, to November 11, 2017, a cohort of 325 asymptomatic Chinese adults meeting the study exclusion criteria was recruited. The radiographs were examined by a spine surgeon and a radiologist to assess the number of thoracic and lumbar vertebrae., Results: In total, 293 volunteers were included in this study: 17 (5.8%) had 11 thoracic vertebrae, and 16 (5.5%) had 6 lumbar vertebrae. Among all volunteers, 12 (4.1%) had 7 cervical vertebrae (C), 11 thoracic vertebrae (T), and 5 lumbar vertebrae (L); 5 (1.7%) had 7C, 11T, and 6L; and 11 (3.8%) had 7C, 12T, and 6L. There was no difference between the findings of the spine surgeon and the radiologist., Conclusions: For the first time, this study describes the rate of presence of 11 thoracic vertebrae and 6 lumbar vertebrae in 293 asymptomatic Chinese adult volunteers. Variations in the number of thoracic and lumbar vertebrae tend to be ignored by spine surgeons. We encourage spinal surgeons and researchers to be aware of such variations when performing thoracic- and lumbar-level surgery and assessing spinal alignment and parameters.