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Purpose: To develop a method for enriching keratinocyte progenitor cells (KPCs) and establish a limbal niche (LN)-mediated transdifferentiation protocol of KPCs into corneal epithelial cells., Methods: Limbal niche cells (LNCs) were isolated from limbal tissues through enzymatic digestion and characterized. Conditioned medium from LNCs cultures was collected. KPCs were enriched by rapid adhesion of Matrigel and subsequently cultured in either an LNCs-conditioned medium supplemented with KSFM (LN-KS) or SHEM (LN-SH) for 14 days. Corneal-specific marker expression was assessed to evaluate transdifferentiation efficiency. Key transcription factors and signaling pathways involved in the transdifferentiation process were identified through single-cell and RNA sequencing, and were validated by western blot and quantitative real-time PCR., Results: Both LN-KS and LN-SH protocols successfully induced corneal epithelial cell transdifferentiation from KPCs, with LN-KS demonstrating higher efficiency in generating CK12 + and p63 + cells (p < 0.001). RNA sequencing analysis and western blot have revealed significant activation of STAT3 and PI3K/AKT signaling pathways. Inhibition of STAT3 blocked the activation of PI3K/AKT signaling pathway and impaired corneal epithelial cell transdifferentiation., Conclusions: This study demonstrates the ability of LN to promote KPCs transdifferentiation into corneal epithelial cells in vitro, and this process is partially mediated by the STAT3/PI3K/AKT signaling pathway., Competing Interests: Declarations. Ethics approval and consent to participate: For animal experiments, the study entitled ‘Transdifferentiation of Rat Keratinocyte Progenitors to Corneal Epithelial Cells by Limbal Niche’ was approved by the Animal Experiment Ethics Committee of Huazhong University of Science and Technology (Date: 10.10.2023, No. 3869) and performed according to the AVMA guidelines. All experimental procedures were conducted in strict accordance with ethical standards for animal research. This research did not involve the use of any human cells, tissues, samples, or cell lines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Preterm and low birth weight infants are at an early stage of development, and do not receive adequate maternal circadian signals. They are often cared for over prolonged periods of hospitalisation in neonatal intensive care units (NICU), where environmental circadian stimuli are lacking. Exposure to artificial light-dark cycles may stimulate the development of the circadian system and improve clinical outcomes. However, it remains uncertain whether cycled light (CL) is preferable to near darkness (ND) or continuous bright light (CBL) in fostering development and maturation, and reducing adverse neonatal health outcomes. This is an update of an earlier Cochrane review, last published in 2016., Objectives: To evaluate the benefits and harms of CL in preterm and low birth weight infants compared to ND or CBL., Search Methods: We searched CENTRAL, PubMed, Embase, and two trial registries to September 2023. We also checked reference lists, and searched for retractions of included studies., Selection Criteria: We included randomised controlled trials (RCTs) or quasi-RCTs in preterm infants (< 37 weeks' postmenstrual age (PMA)), or those with a low birth weight (< 2500 g), admitted and cared for in an NICU or a step-down unit, comparing CL with ND or CBL., Data Collection and Analysis: We used the standard review methods of the Cochrane Neonatal Review Group to assess the methodological quality of studies. We used the fixed-effect model with risk ratio (RR) and mean difference (MD), with their 95% confidence intervals (CIs) for dichotomous data. Our primary outcomes were (1) growth at three and six months' corrected age, (2) major neurodevelopmental disability, and (3) adverse effects. Our secondary outcomes were (4) retinopathy of prematurity, (5) duration of initial hospitalisation, (6) duration of oxygen treatment, and (7) parent satisfaction. We used GRADE to assess the certainty of evidence for each outcome., Main Results: We included 20 studies with 1633 infants. Data for meta-analysis were available for 11 studies (1126 infants). One study with multiple arms was included in both comparisons. We rated the overall risk of bias at the study level as high or unclear for all 20 studies that had one or several unclear or high risk of bias judgements across the domains. Cycled light versus dimmed light or near darkness (10 studies) The evidence is very uncertain about the effect of cycled light compared to dimmed light (reduction of illumination levels) or near darkness on weight at three months (MD 24.79, 95% CI -262.33 to 311.91; 2 studies, 187 infants; very low-certainty evidence), and weight at six months (MD 202, 95% CI -109.68 to 513.68; 1 study, 147 infants; very low-certainty evidence). The studies did not report any data for major neurodevelopmental disability. No data are available for adverse effects; it is uncertain if the absence of adverse effects is because none occurred, or because they were not identified and recorded. The evidence is very uncertain about the effect of cycled light compared to dimmed light or near darkness on the likelihood of developing retinopathy of prematurity of any stage (RR 0.89, 95% CI 0.76 to 1.03; 3 studies, 307 infants; very low-certainty evidence), and severe retinopathy of prematurity of stage 3 or higher (RR 0.98, 95% CI 0.59 to 1.61; 4 studies, 454 infants; very low-certainty evidence). Cycled light compared to dimmed light or near darkness may have little to no effect on the duration of initial hospitalisation (MD -3.04, 95% CI -7.86 to 1.78; 5 studies, 550 infants; very low-certainty evidence), but the evidence is very uncertain. Cycled light versus continuous bright light (11 studies) No data are available on the following primary outcomes, as no studies reported them: growth at three and six months' corrected age, major neurodevelopmental disability, and adverse effects. It is uncertain if the absence of adverse effects is because none occurred or because they were not identified and recorded. No data are available on retinopathy of prematurity, as no studies reported it. Cycled light compared to continuous bright light may reduce the duration of initial hospitalisation, but the evidence is very uncertain (MD -9.86, 95% CI -10.09 to -9.63; 5 studies, 499 infants; very low-certainty evidence)., Authors' Conclusions: Despite identifying 20 studies, we remain uncertain about the effect of CL compared to ND or CBL on all outcomes of interest in this review. In addition, a few critical outcomes were not reported by any of the included studies. The evidence remains uncertain about whether CL is the right choice in the NICU. The physician should always weigh the benefits and risks, based on the effects of the different options in the specific setting., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The fall armyworm (FAW), Spodoptera frugiperda, has colonized and caused consistent damage in the Eastern hemisphere. The identification of various FAW strains is essential for developing precise prevention and control measures. The triosephosphate isomerase (Tpi) gene is recognized as an effective marker closely linked to FAW subpopulations. However, most current studies primarily focus on the comparison of variations in specific gene sites of this gene. In this study, we conducted full-length sequencing of the Tpi genes from 5 representative FAW groups. Our findings revealed that the Tpi genes varied in length from 1220 to 1420 bp, with the primary variation occurring within 4 introns. Notably, the exon lengths remained consistent, at 747 bp, with 37 observed base variations; however, no amino acid variations were detected. Through sequence alignment, we identified 8 stable variation sites that can be used to distinguish FAW strains in the Eastern hemisphere. Additionally, we performed strain identification on 1569 FAW samples collected from 19 provinces in China between 2020 and 2021. The extensive analysis indicated the absence of the rice strain in the samples. Instead, we only detected the presence of the corn strain and the Zambia strain, with the Zambia strain being distributed in a very low proportion (3.44%). Furthermore, the corn strain could be further categorized into 2 subgroups. This comprehensive study provides a valuable reference for enhancing our understanding of FAW population differentiation and for improving monitoring and early warning efforts., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Intertemporal decision making is the process by which individuals make judgments or choices regarding outcomes that occur at different times. Although intertemporal decision making is widely investigated, most studies explore it in terms of individual decision making, while neglecting group decision making, which holds more practical significance and adaptive value. This study recommends adopting a "two-process" approach that uses self-assessment questionnaires, audiovisual recordings, and visual decision-making tools to quantify interpersonal interaction processes and information processing in group intertemporal decision-making settings. In this way, studies can reveal the psychological and theoretical mechanisms of the group intertemporal decision-making process. At the level of interpersonal interaction processes, such an approach can identify the differential mechanisms between group and individual intertemporal decision making. In terms of information processing, it can reveal the mechanisms of the decision-making process in group intertemporal decision making. The findings of such work can provide a basis for interventions and nudges that encourage more visionary group intertemporal decision making.

This study elucidates the mechanisms and principles governing chemoselectivity in synthesizing two distinct N-heterocycles, benzimidazole thiazine and benzothiazole imidazole, through BF 3 •OEt 2 -catalyzed cyclization reactions of propargyl alcohols with benzimidazole thiols. Employing density functional theory calculations, we highlight the crucial role of fluorine source in influencing chemoselectivity. In DCM, BF 3 , as the catalytic center, coordinates with propargyl alcohol's hydroxyl group to form a precursor. Conversely, in DMF, [BF 2 •DMF] + , formed from DMF and BF 3 •OEt 2 , acts as the catalytic center, activating the propargyl alcohol's hydroxyl group. The mechanisms in both solvents involve sequential steps: B-O bond formation, C-O bond cleavage, S-C bond formation, hydrogen atom transfer (HAT), cyclization, and deprotonation. A notable difference is the HAT process: in DCM, it follows a 1,5-HAT process, while in DMF, BF 4 - formation from DMF and BF 3 •OEt 2 provides a fluorine source and introduces steric hindrance, favoring a 1,6-HAT process and leading to unique chemoselectivity. This pioneering research showcases the impact of DMF on cyclization reactions, offering valuable insights for comprehending and designing reactions driven by fluorine sources. Crucially, our results propose an innovative reaction mechanism featuring lower potential energy surfaces, enhancing our understanding of the intricate interplay among reactants, catalysts, and solvents.

Herpesviruses replicate by cleaving concatemeric dsDNA into single genomic units that are packaged through an oligomeric portal present in preformed procapsids. In contrast to what is known about phage portal proteins, details concerning herpesvirus portal structure and function are not as well understood. A panel of 65 Varicella-Zoster virus (VZV) recombinant portal proteins with five amino acid in-frame insertions were generated by random transposon mutagenesis of the VZV portal gene, ORF54. Subsequently, 65 VZV LUC recombinant viruses (TNs) were generated via recombineering. Insertions were mapped to predicted portal domains (clip, wing, stem, wall, crown, and β-hairpin tunnel-loop) and recombinant viruses were characterized for plaque morphology, replication kinetics, pORF54 expression, and classified based on replication in non-complementing (ARPE19) or complementing (ARPE54C50) cell lines. The N- and C-termini were tolerant to insertion mutagenesis, as were certain clip sub-domains. The majority of mutants mapping to the wing, wall, β-hairpin tunnel loop, and stem domains were lethal. Elimination of the predicted ORF54 start codon revealed that the first 40 amino acids of the N-terminus were not required for viral replication. Stop codon insertions in the C-terminus showed that the last 100 amino acids were not required for viral replication. Lastly, a putative protease cleavage site was identified in the C-terminus of pORF54. Cleavage was likely orchestrated by a viral protease; however, processing was not required for DNA encapsidation and viral replication. The panel of recombinants should prove valuable in future studies to dissect mammalian portal structure and function.IMPORTANCEThough nucleoside analogs and a live-attenuated vaccine are currently available to treat some human herpesvirus family members, alternate methods of combating herpesvirus infection could include blocking viral replication at the DNA encapsidation stage. The approval of Letermovir provided proof of concept regarding the use of encapsidation inhibitors to treat herpesvirus infections in the clinic. We propose that small-molecule compounds could be employed to interrupt portal oligomerization, assembly into the capsid vertex, or affect portal function/dynamics. Targeting portal at any of these steps would result in disruption of viral DNA packaging and a decrease or absence of mature infectious herpesvirus particles. The oligomeric portals of herpesviruses are structurally conserved, and therefore, it may be possible to find a single compound capable of targeting portals from one or more of the herpesvirus subfamilies. Drug candidates from such a series would be effective against viruses resistant to the currently available antivirals., Competing Interests: The authors declare no conflict of interest.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo., Methods: MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo., Results: In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect., Conclusion: SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.

Purpose: The aim of this study was to report the first case of mycotic keratitis caused by Botryosphaeria dothidea ., Methods: A 29-year-old man developed a fungal infection after being hit with chestnut thorns in the left eye. In vivo confocal microscopy, microbial culture, and next-generation sequencing (NGS) were used in the diagnosis of mycotic keratitis., Results: The patient was provisionally diagnosed with mycotic keratitis based on IVCM and promptly received local and systemic antifungal treatment with voriconazole and amphotericin B. Although microbial culture failed to identify the pathogen, NGS revealed B. dothidea as the causative agent. Although the infection was quickly contained, corneal perforation still occurred. Owing to the lack of fresh donor corneas, the patient underwent multilayer amniotic membrane and conjunctival pedicle graft surgery. The infection was successfully controlled, and during the 6-month follow-up, the cornea remained clear in the inferotemporal optical zone., Conclusions: We report a novel phytopathogen- B. dothidea -causing mycotic keratitis . Our case indicates that B. dothidea responds well to voriconazole and amphotericin therapy. This case broadens the spectrum of fungal keratitis and highlights the application of NGS in identifying molds., Competing Interests: The authors indicate no potential conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Six new isoquinoline alkaloids, including aporphine alkaloids ( 2 , 3 , 9 , and 10 ), a benzylisoquinoline alkaloid ( 13 ), and a protoberberine alkaloid ( 17 ), were isolated from the roots of Fissistigma polyanthum , along with a new furanone ( 20 ) and 13 known isoquinoline alkaloids ( 1 , 4 - 8 , 11 , 12 , 14 - 16 , 18 , and 19 ). The structures of the new compounds were elucidated by the analysis of spectroscopic data. Compounds 1 and 2 are rare oxalyl-fused dehydroaporphine alkaloids. Compound 12 presented the most potent dual-target activities on AChE inhibition and Aβ aggregation inhibition, while compounds 13 and 19 simultaneously exhibited discernible AChE and BChE inhibitions with antioxidant activities. The activity results indicate that F. polyanthum alkaloids have a potential of inhibition and prevention of Alzheimer's disease mainly through both ChEs and β-amyloid pathways in addition to antioxidant activity.

Introduction: The development of insecticide resistance in Spodoptera frugiperda populations is a serious threat to the crop industry. Given the spread of invasive resistant populations, prospective monitoring should be accelerated, and the development of diagnostic tools for rapid and accurate assessments of insecticide resistance is essential. Methods: First, the discriminating dose and diagnostic time of the kit were determined by the glass vial method based on a susceptible strain. Then, pests that were collected from field populations were used to determine their susceptibility to seven insecticides by using the diagnostic kit. Finally, the accuracy of the kit was verified based on correlation analyses and the likelihood of insecticide control failure was assessed. Results: Here, we describe a diagnostic kit that enables the rapid detection of resistance to chlorpyrifos, bifenthrin, deltamethrin, lambda-cyhalothrin, phoxim, chlorantraniliprole and chlorfenapyr within 1-2 h in S. frugiperda at diagnostic doses of 0.98, 0.84, 0.38, 1.64, 0.0082, 1.75 and 0.65 μg/cm 2 , respectively. The linear equation between mortalities under diagnostic doses and actual resistance ratios measured by the diet-overlay bioassay was determined. The high correlation indicates that the insecticide resistance levels diagnosed by the kit were consistent with the results of the diet-overlay bioassay. Moreover, we found a significant negative correlation between diagnostic mortality and the likelihood of control failure for bifenthrin ( r = -0.899, p = 0.001), deltamethrin ( r = -0.737, p = 0.024) and lambda-cyhalothrin ( r = -0.871, p = 0.002). Discussion: The insecticide resistance diagnostic kit for S. frugiperda is a user-friendly tool (portable, short detection time). Its excellent performance qualifies the kit as a reliable screening tool for identifying effective insecticides in sustainable resistance management., 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 © 2023 Mao, Li, Zhu, Jin, Wang, Peng and Xiao.)

Rheumatoid arthritis (RA) is a refractory autoimmune disease, affecting about 1% of the world's population. RA is divided into seronegative RA and seropositive RA. However, biomarkers for discriminating between seronegative and seropositive RA have not been reported. In this study, we profiled serum miRNAs in seronegative RA patients (N-RA), seropositive RA patients (P-RA) and healthy controls (HC) by small RNA sequencing. Results indicated that compared with HC group, there were one up-regulated and four downregulated miRNAs in N-RA group (fold change ≥ 2 and P value < 0.05); compared with P-RA group, there were two up-regulated and four downregulated miRNAs in N-RA group; compared with HC group, there were three up-regulated and four downregulated miRNAs in P-RA group. Among them, the level of hsa-miR-362-5p in N-RA group was up-regulated compared with that in HC group and P-RA group, and the level of hsa-miR-6855-5p and hsa-miR-187-3p in P-RA group was upregulated compared with that in N-RA group and HC group. Validation by qPCR confirmed that serum hsa-miR-362-5p level was elevated in N-RA group. Subsequently, by analyzing the target genes using RNAhybrid, PITA, Miranda and TargetScan and functions of differential miRNAs utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the target genes and molecular pathways regulated by miRNAs in seronegative RA and seropositive RA were roughly the same, and miRNAs in these two diseases may participate in the occurrence and development of diseases by regulating the immune system. In conclusion, this study revealed the profiles of serum miRNAs in seronegative and seropositive RA patients for the first time, providing potential biomarkers and targets for the diagnosis and treatment of seronegative and seropositive RA., Competing Interests: The authors declare that they have no competing interests., (© 2023 He et al.)

Meibomian glands (MGs) are vital for ocular surface health. However, the roles of inflammation in the progression of meibomian gland dysfunction (MGD) are largely unknown. In this study, the roles of the inflammation factor interleukin-1β (IL-1β) via the p38 mitogen-activated protein kinases (MAPK) signaling pathway on rat meibomian gland epithelial cells (RMGECs) were explored. Eyelids from adult rat mice at 2 months and 2 years of age were stained with specific antibodies against IL-1β to identify inflammation levels. RMGECs were exposed to IL-1β and/or SB203580, a specific inhibitor of p38 MAPK signaling pathway, for 3 days. Cell proliferation, keratinization, lipid accumulation, and matrix metalloproteinases 9 (MMP9) expression were evaluated by MTT assay, polymerase chain reaction (PCR), immunofluorescence staining, apoptosis assay, lipid staining, and Western blot analyses. We found that IL-1β was significantly higher in the terminal ducts of MGs in rats with age-related MGD than in young rats. IL-1β inhibited cell proliferation, suppressed lipid accumulation and peroxisome proliferator activator receptor γ (PPARγ) expression, and promoted apoptosis while activating the p38 MAPK signaling pathway. Cytokeratin 1 (CK1), a marker for complete keratinization, and MMP9 in RMGECs were also up-regulated by IL-1β. SB203580 effectively diminished the effects of IL-1β on differentiation, keratinization, and MMP9 expression by blocking IL-1β-induced p38 MAPK activation, although it also inhibited cell proliferation. The inhibition of the p38 MAPK signaling pathway blocked IL-1β-induced differentiation reduction, hyperkeratinization, and MMP9 overexpression of RMGECs, which provides a potential therapy for MGD., Competing Interests: Declaration of competing interest All authors indicate no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Blepharospasm patients often have dry eye manifestations. Botulinum neurotoxin type A (BoNT-A) injection has been the main management for blepharospasm and absorbable punctal plug (APP) insertion is shown to be effective in the treatment of dry eye. However, there have been no studies investigating the combined treatment of BoNT-A and APP in blepharospasm patients with dry eye. In this retrospective study, 17 blepharospasm patients with dry eye treated by BoNT-A injection and 12 receiving BoNT-A plus APP treatment were enrolled. The efficacy was evaluated according to the Jankovic rating scale, Ocular Surface Disease Index (OSDI), fluorescein staining (FL), fluorescein tear break-up time (FBUT) and Schirmer I test (SIT). Both BoNT-A and BoNT-A+APP treatment effectively reduced the functional impairment of blepharospasm. At baseline, all the patients had high OSDI scores (BoNT-A group: 82.48 ± 7.37, BoNT-A+APP group: 78.82 ± 4.60, p = 0.112), but relatively low degrees of FL (BoNT-A group: 3.18 ± 1.01, BoNT-A+APP group: 3.50 ± 1.24, p = 0.466), FBUT (BoNT-A group: 1.71 ± 0.77, BoNT-A+APP group: 2.17 ± 0.58, p = 0.077) and SIT (BoNT-A group: 2.53 ± 0.99, BoNT-A+APP group: 3.17 ± 1.23, p = 0.153). After treatment, OSDI, FL, FBUT and SIT were all obviously restored in the two groups. When comparing the changing rates, only OSDI (BoNT-A group: -52.23% ± 15.57%, BoNT-A+APP group: -61.84% ± 9.10%, p = 0.047) and FL (BoNT-A group: -22.55% ± 25.98%, BoNT-A+APP group: -41.94% ± 14.46%, p = 0.016) showed significant differences between the two groups. This study suggests that OSDI is not applicable in the diagnosis of dry eye among blepharospasm patients. For blepharospasm patients with severe dry eye symptoms, especially those with fluorescein staining in the cornea, the combined treatment of BoNT-A and APP is more effective than using BoNT-A alone.

Objective: To investigate hepatic perivascular epithelioid cell tumor (PEComa) diagnosis and treatment plan. Methods: 24 cases diagnosed with PEComa clinical manifestations, serum alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), imaging findings, surgical methods, postoperative hospital stay, pathological results and prognosis were analyzed retrospectively from September 2015 to September 2020. Results: Majority of patients were females (79.2%), aged 41.5±11.4 years. Tumors were predominantly located in the right liver (50.0%). 76.7% of the cases were mostly clinically asymptomatic. AFP, CEA and CA199 indices were all negative. CT mostly showed low density tumor in the plain scan phase, enhanced in the enhancement phase, and enhanced and weakened in portal venous and equilibrium phase (66.7%). MRI manifestations of most tumors were hypointense on T 1 WI and hyperintense on T 2 WI (72.7%). B-ultrasound mostly showed hyperechoic mass in the tumor area with punctate vascular shadow (52.9%). Postoperative hospital stay was 9.0±2.4 days for laparoscopic surgery patients ( n =13), 13.4±6.3 days for traditional laparotomy (hereinafter referred to as laparotomy, n =10), and 3 days for 1 patient with microwave ablation. All postoperative pathological results were positive for HMB45 and Melan-A. Follow-up results: 21 cases survived normally, with no tumor recurrence in the recent physical examination; two cases had tumor recurrence and they died two and three years after surgery, and one case was lost to follow-up. Conclusion: Hepatic PEComa more commonly occurs in middle-aged women, with no specific features for tumor markers and clinical manifestations. Some imaging findings are specific, so its features can be combined as a basis for diagnosis. Postoperative pathological examination results can confirm the diagnosis. Therefore, surgery remains the initial treatment plan. Microwave ablation and laparoscopic surgery are recommended as the preferred option because of shorter hospital stays and less trauma than open surgery.

Chitosan loaded with silica foliar spraying material (NCSI) was prepared using natural biomass chitosan and organic silicon and was applied to Lindao 16, Nanjing 2728, Zhenghan 10, and Nongken 58 at the rice filling stage to study the effects on arsenic (As) absorption in rice. The results showed that under a 100 μmol·L -1 pentavalent arsenic[As(Ⅴ)] hydroponic environment, foliar spraying of 30 mL NCSI on leaves promoted the accumulation of As in leaves and reduced the accumulation of As in roots and grains. Among them, the As contents of Nanjing 2728, Zhenghan 10, and Nongken 58 grains were decreased by 14.44%, 21.66%, and 10.85%, respectively, compared with those of the blank group on the 3 rd day after spraying NCSI. Meanwhile, foliar spraying of NCSI improved the activities of CAT and SOD in rice leaves and increased the GSH content, indicating that the spraying of NCSI alleviated the stress of As on rice, improved the tolerance of rice to As, and reduced the toxicity of As to rice. The main mechanism of foliar application of NCSI to reduce As accumulation in rice grains may have been that NCSI induced GSH production in leaves, reducing more As(Ⅴ) to trivalent arsenic[As(Ⅲ)], thereby promoting As chelating in leaves and inhibiting As migration to grains. Therefore, foliar spraying of NCSI can be used as a foliar control technology to solve the problem of excessive As in rice and provide a scientific basis for the safe production of rice in China.

Objective: To identify the relation of microvascular density (MVD) to the early postoperative recurrence and metastasis of T1 esophageal squamous cell carcinoma, and to determine whether MVD could be a prognostic predictor of esophageal squamous cell carcinoma., Methods: Patients with T1 esophageal squamous cell carcinoma were enrolled. Immunohistochemistry with primary antibody against CD-34 was performed to count MVD. ROC curve was plotted and appropriate cutoff value was determined to evaluate the potential power of MVD in predicting early recurrence and metastasis of T1 esophageal squamous cell carcinoma. Survival curves were drawn by the Kaplan-Meier method and significance were tested by the Mantel-Cox test., Results: A total of 37 patients with T1 esophageal squamous cell carcinoma were enrolled. The MVD of T1 esophageal squamous cell carcinoma patients with early metastasis was significantly higher than that of T1 esophageal squamous cell carcinoma patients without early metastasis (65.83±4.39 vs. 42.26±2.34, p <0.001). MVD was available in distinguishing whether patients with early esophageal are prone to postoperative recurrence or metastasis (AUC=0.861; 95% CI 0.738-0.984, p <0.001), with 88.89% sensitivity and 68.42% specificity of MVD being obtained when the cut-off is 44.5. Kaplan-Meier survival curves showed that patients with a higher MVD had a lower survival (37.35 months) compared with those with low MVD (40.79 months) ( p <0.05)., Conclusions: MVD could be a promising indicator for early postoperative recurrence and metastasis of T1 esophageal squamous cell carcinoma and the prognosis of these patients., (© 2022 by the Association of Clinical Scientists, Inc.)

Prostate cancer (PCa) affects millions of men globally. Due to advances in understanding genomic landscapes and biological functions, the treatment of PCa continues to improve. Recently, various new classes of agents, which include next-generation androgen receptor (AR) signaling inhibitors (abiraterone, enzalutamide, apalutamide, and darolutamide), bone-targeting agents (radium-223 chloride, zoledronic acid), and poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib, rucaparib, and talazoparib) have been developed to treat PCa. Agents targeting other signaling pathways, including cyclin-dependent kinase (CDK)4/6, Ak strain transforming (AKT), wingless-type protein (WNT), and epigenetic marks, have successively entered clinical trials. Furthermore, prostate-specific membrane antigen (PSMA) targeting agents such as 177 Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic efficacy. Advanced clinical studies with immune checkpoint inhibitors (ICIs) have shown limited benefits in PCa, whereas subgroups of PCa with mismatch repair (MMR) or CDK12 inactivation may benefit from ICIs treatment. In this review, we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms, and further discussed their limitations and future directions., (© 2022. The Author(s).)

Objective: To evaluate the efficacy and safety of laparoscopic surgery for perivascular epithelioid cell tumor (PEComa). Methods: The clinical data of 42 patients with hepatic PEComa diagnosed by pathology in Hunan Provincial People's Hospital from September 2012 to September 2021 were retrospectively analyzed. The patients were divided into the endoscopic group and the open group according to surgical methods. Statistical software was used to compare the differences in operation time, intraoperative blood loss, postoperative hospital stay, postoperative pathological data and incidence of complications between the two groups. Results: There were 27 cases in the endoscopic group and 15 cases in the open group. In the endoscopic group, there were 5 males and 22 females, aged (40.0±10.4) years. In the open group, there were 5 males and 10 females, aged (44.5±12.6) years. The operative time of the endoscopic group and the open group was (239±156.2) min and (348±103.0) min, and the postoperative hospital stay was (8.2±2.4) d and (13.7±4.9) d, respectively, the endoscopic group was significantly better than the open group, and the difference was statistically significant ( P <0.05). There was no significant difference in intraoperative blood loss, tumor benign and malignant, tumor site, tumor diameter, Ki67 index, postoperative complications such as biliary leakage, incision infection and pleural effusion ( P >0.05). During the follow-up period of 2-103 months, one case was lost to follow-up, two cases died in the endoscopic group,one case died in the open group. The 5-year overall survival rate (OS) and disease-free survival rate (DFS) were 80.8% and 83.0%, respectively. Meanwhile,. The 5-year OS and DFS were both 92.3%, the difference was not statistically significant ( P >0.05). Conclusions: Laparoscopic treatment of hepatic PEComa has the advantages of short operation time and short postoperative hospital stay, and the incidence of complications, 5-year OS and DFS are not significantly different from that of the open group.

Background: The RESORCE trial reported that regorafenib was effective as the second-line treatment for patients with hepatocellular carcinoma (HCC) after progression on sorafenib. Real-world data are needed to assess clinical outcomes and adverse events in the setting of daily practice. Objective: We aimed to evaluate the efficacy and safety of regorafenib after disease progression with sorafenib in Chinese patients with advanced HCC. Patients and Methods: A total of 41 patients with advanced HCC who did not respond to sorafenib and followed a regorafenib regimen were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), radiological responses, and adverse events (AEs) were evaluated. Survival curves were compared by using the log-rank test and constructed with the Kaplan-Meier method. Results: The median PFS with regorafenib was 6.6 months (range: 5.0-8.2 months), and the median OS with regorafenib was not reached. The 1-year OS rate of regorafenib was 66.4%. The median OS of sequential sorafenib to regorafenib treatment was 35.3 months [95% confidence interval (CI), 24.3-46.3], and the 2-year OS rate of sequential sorafenib to regorafenib treatment was 74.4%. The most common AEs of regorafenib treatment were elevated aspartate aminotransferase [17/41 patients (41.5%)], elevated alanine aminotransferase [16/41 patients (39%)] and hand-foot syndrome [14/41 patients (34.1%)]. Conclusion: Regorafenib appears to be safe and clinically effective in patients with advanced HCC who progressed on first-line sorafenib., 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 © 2022 Hou, Xiao, Huang, Jiang, Jiang, Li, Xu and Chen.)

Purpose: To report a 10-year follow-up case of the first lamellar keratoplasty treatment with acellular porcine corneal stroma (APCS)., Methods: A 62-year-old woman was diagnosed with a fungal corneal ulcer and received lamellar keratoplasty treatment with APCS in 2010. The 10-year follow-up results were evaluated by slit lamp biomicroscopy, anterior segment optical coherence tomography, in vivo confocal microscopy, and corneal biomechanics analysis., Results: The APCS graft maintained good biocompatibility and physical properties in transparency, stromal regeneration, elasticity, and deformation resistance. However, some disadvantages were observed, including a protracted course to eventual clearing, a decreased thickness, corneal depositions, sparsely distributed neural fibers, and low stiffness., Conclusions: This case indicated that APCS remains stable over a 10-year follow-up period. APCS can serve as a functional stromal surrogate where donor human corneal tissue is unavailable., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Immunotherapies targeting immune checkpoint molecules have shown promising treatment for a subset of cancers; however, many "cold" tumors, such as prostate cancer, remain unresponsive. We aimed to identify a potential targetable marker relevant to prostate cancer and develop novel immunotherapy., Experimental Design: Analysis of transcriptomic profiles at single-cell resolution was performed in clinical patients' samples, along with integrated analysis of multiple RNA-sequencing datasets. The antitumor activity of YY001, a novel EP4 antagonist, combined with anti-programmed cell death protein 1 (PD-1) antibody was evaluated both in vitro and in vivo ., Results: We identified EP4 (PTGER4) as expressed in epithelial cells and various immune cells and involved in modulating the prostate cancer immune microenvironment. YY001, a novel EP4 antagonist, inhibited the differentiation, maturation, and immunosuppressive function of myeloid-derived suppressor cells (MDSC) while enhancing the proliferation and anticancer functions of T cells. Furthermore, it reversed the infiltration levels of MDSCs and T cells in the tumor microenvironment by overturning the chemokine profile of tumor cells in vitro and in vivo . The combined immunotherapy demonstrated a robust antitumor immune response as indicated by the robust accumulation and activation of CD8 + cytotoxic T cells, with a significantly decreased MDSC ratio and reduced MDSC immunosuppression function., Conclusions: Our study identified EP4 as a specific target for prostate cancer immunotherapy and demonstrated that YY001 inhibited the growth of prostate tumors by regulating the immune microenvironment and strongly synergized with anti-PD-1 antibodies to convert completely unresponsive prostate cancers into responsive cancers, resulting in marked tumor regression, long-term survival, and lasting immunologic memory., (©2021 American Association for Cancer Research.)

Background: The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to demonstrate the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) for treating OMPC., Methods: The present study will be conducted as a prospective, open-label, dose-escalation, phase I/II clinical trial. The patients with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 4-8 weeks after radiotherapy, and ADT will be continued for 2 years. The primary endpoints of the study are safety profiles, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading scale, and perioperativemorbidities, assessed by the Clavien-Dindo classification system. The secondary endpoints include positive surgical margin (pSM), biochemical recurrence-free survival (bPFS), radiological progression-free survival (RPFS), postoperative continence, and quality of life (QoL) parameters., Discussion: The optimal treatment for OMPC is still on its way, prompting investigation for novel multimodality treatment protocol for this patient population. Traditionally, radical prostatectomy has been recommended as one of the standard therapies for localized prostate cancer, but indications have expanded over the years as recommended by NCCN and EAU guidelines. RP has been carried out in some centres for OMPC patients, but its value has been inconclusive, showing elevated complication risks and limited survival benefit. Neoadjuvant radiotherapy has been proven safe and effective in colorectal cancer, breast cancer and other various types of malignant tumors, showing potential advantages in terms of reducing metastatic stem-cell activity, providing clinical downstaging, and reducing potential intraoperative risks. Existing trials have shown that naRT is well tolerated for high-risk and locally-advanced prostate cancer. In this study, we hope to further determine the optimal irradiation dose and patient tolerance for genitourinary, gastrointestinal and systemic toxicities with the design of 3+3 dose escalation; also, final pathology can be obtained following RP to further determine treatment response and follow-up treatment plans., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900025743. http://www.chictr.org.cn/showprojen.aspx?proj=43065.

In this study, we present a wavelength sensor that is capable of distinguishing the spectrum in the range from ultraviolet (UV) to near-infrared (NIR) light. The filterless device is composed of two horizontally stacking PdSe 2 /20 μm Si/PdSe 2 heterojunction photodetectors with a photovoltaic (PV) behavior, which makes it possible for the device to work at 0 bias voltage. Due to the relatively small thickness of Si and the wavelength-dependent absorption coefficient, the two PdSe 2 /20 μm Si/PdSe 2 photodetectors according to theoretical simulation display a sharp contrast in distribution of the photoabsorption rate. As a result, the photocurrents of both photodetectors evolve in completely different ways with increasing wavelengths, leading to a monotonic decrease in the photocurrent ratio from 6800 to 22 when the wavelength gradually increases from 265 to 1050 nm. The corresponding relationship between both the photocurrent ratio and wavelength can be easily described by the monotonic function, which can help to precisely determine the wavelength in the range from 265 to 1050 nm, with an average relative error less than ±1.6%. It is also revealed that by slightly revising the monotonic function, the wavelength in other different temperatures can also be estimated.

Currently, the aquatic environment of the Tuojiang River basin in Sichuan Province is severely polluted by non-point sources of total nitrogen (TN). This study adopts the pollution discharge coefficient method to estimate the TN pollution load of non-point sources in this watershed during 2007-2017. The temporal and spatial distribution and transfer trends of the TN pollution load in the Tuojiang River basin were examined, based on center-of-gravity statistical and spatial analysis technology. This study aimed to provide an accurate theoretical basis for the prevention and early identification of non-point source pollution in the Tuojiang River basin. The results indicate that livestock breeding was the main non-point source of TN pollution and contributed more than 45% to the TN pollution load during 2007-2017. The contribution rate of rural life and domestic waste decreased continually during the study period, whereas that of farmland solid waste and farmland runoff exhibited an increasing trend. The total pollution load of TN exhibited a decreasing trend during 2007-2017. The maximum and minimum TN pollution loads occurred in 2010 and 2017 with values of 5.7×10 4 t and 4.69×10 4 t, respectively. Spatial heterogeneity of the pollution load, together with the uneven distribution of rainfall runoff, caused a shift from northwest to southeast in the pollution-load centers of gravity for livestock and poultry breeding, farmland solid waste, and farmland runoff. Southeast of the watershed is the key area for prevention and control of these pollution sources. A shift in the centers of gravity for rural living and household waste pollution, from southeast to northwest, was attributed to agricultural populations transforming to urban populations in the southeastern counties. The maximum transfer range was 66.35 km 2 , and this minimum boundary circle is the key identification area of pollution source pollution load change. Northwest of Tuojiang River basin is the key area in which TN pollution from rural living and rural household waste can be prevented. This research expands the methods for exploring the temporal and spatial evolution of pollution load in the Tuojiang River basin, which is of great significance for improving the aquatic environment and promoting sustainable development of the basin economy.

Androgen receptor-positive prostate cancer (PCa) and estrogen receptor-positive luminal breast cancer (BCa) are generally less responsive to immunotherapy compared with certain tumor types such as melanoma. However, the underlying mechanisms are not fully elucidated. In this study, we found that FOXA1 overexpression inversely correlated with interferon (IFN) signature and antigen presentation gene expression in PCa and BCa patients. FOXA1 bound the STAT2 DNA-binding domain and suppressed STAT2 DNA-binding activity, IFN signaling gene expression, and cancer immune response independently of the transactivation activity of FOXA1 and its mutations detected in PCa and BCa. Increased FOXA1 expression promoted cancer immuno- and chemotherapy resistance in mice and PCa and BCa patients. These findings were also validated in bladder cancer expressing high levels of FOXA1. FOXA1 overexpression could be a prognostic factor to predict therapy resistance and a viable target to sensitize luminal PCa, BCa, and bladder cancer to immuno- and chemotherapy.

A wavelength sensor as a representative optoelectronic device plays an important role in many fields including visible light communication, medical diagnosis, and image recognition. In this study, a wavelength-sensitive detector with a new operation mechanism was reported. The as-proposed wavelength sensor which is composed of two parallel PtSe 2 /thin Si Schottky junction photodetectors is capable of distinguishing wavelength in the range from ultraviolet to near infrared (UV-NIR) light (265 to 1050 nm), in that the relationship between the photocurrent ratio of both photodetectors and incident wavelength can be numerically described by a monotonic function. The unique operation mechanism of the thin Si based wavelength sensor was unveiled by theoretical simulation based on Synopsys Sentaurus Technology Computer Aided Design (TCAD). Remarkably, the wavelength sensor has an average absolute error of ±4.05 nm and an average relative error less than ±0.56%, which are much better than previously reported devices. What is more, extensive analysis was performed to reveal how and to what extent the working temperature and incident light intensity, and the thickness of the PtSe 2 layer will influence the performance of the wavelength sensor.

Rat limbal niche cells (LNCs) have been proven to induce transdifferentiation of oral mucosal epithelial cells (OMECs) into corneal epithelial-like cells termed transdifferentiated oral mucosal epithelial cells (T-OMECs). This investigation aimed to evaluate the effect of subconjunctival T-OMEC injections on alkali-induced limbal stem cell deficiency (LSCD) in rats. LNCs were cocultured with OMECs in the Transwell system to obtain T-OMECs, with NIH-3T3 cells serving as a control. Subconjunctival injection of single T-OMEC or OMEC suspension was performed immediately after corneal alkali injury. T-OMECs were prelabeled with the fluorescent dye CM-DiI in vitro and tracked in vivo. Corneal epithelial defect, opacity, and neovascularization were quantitatively analyzed. The degree of corneal epithelial defect (from day 1 onward), opacity (from day 5 onward), and neovascularization (from day 2 onward) was significantly less in the T-OMEC group than in the OMEC group. Cytokeratin 12 (CK12), pigment epithelium-derived factor, and soluble fms-like tyrosine kinase-1 were expressed at a higher rate following T-OMEC injection. Some CM-DiI-labeled cells were found to be coexpressed with CK12, Pax6, and ΔNp63α in the corneal epithelium after subconjunctival injection. Subconjunctival injection of T-OMECs prevents conjunctival invasion and maintains a normal corneal phenotype, which might be a novel strategy in the treatment of LSCD.

Purpose: Meibomian glands play a vital role in maintaining ocular surface stability. This study aimed to investigate whether Hedgehog signaling is involved in the regulation of meibomian gland epithelial cells., Methods: Rat meibomian glands epithelial cells (RMGECs) were isolated from ducts and ductules, and then were cultivated to passage two on Matrigel coated wells in meibomian gland epithelial cells medium (MGECM). Cells were switched from MGECM to differentiation medium (DM) or DM added 10 µg/mL azithromycin (DM + AZM) when reached 50% to 60% confluence. The effects of the Smoothened (Smo) agonist (Smo agonist [SAG]) and antagonist (by cyclopamine) on RMGECs were analyzed using quantitative RT-PCR, cell proliferation analysis, immunofluorescence staining, and Nile red staining., Results: The Hedgehog receptor, Smo, and its downstream molecules, Glis, were expressed both in vivo and in vitro. Smo and Gli1 both decreased with the increase of differentiation in vitro. Smo antagonist, cyclopamine, reduced cell numbers, and the expression of Ki67 in MGECM, and promoted the expression of SREBP1 and lipid production in DM + AZM. Smo agonist, SAG, inhibited the expression of SREBP1 and lipid accumulation in DM + AZM but showed no significant effects on raising cell numbers and the expression of Ki67 in MGECM., Conclusions: The Hedgehog signaling pathway appears to play important roles in RMGECs proliferation and differentiation. This may provide a potential therapeutic way to treat meibomian gland dysfunction (MGD).

Prostate cancer shows remarkable clinical heterogeneity, which manifests in spatial and clonal genomic diversity. By contrast, the transcriptomic heterogeneity of prostate tumours is poorly understood. Here we have profiled the transcriptomes of 36,424 single cells from 13 prostate tumours and identified the epithelial cells underlying disease aggressiveness. The tumour microenvironment (TME) showed activation of multiple progression-associated transcriptomic programs. Notably, we observed promiscuous KLK3 expression and validated the ability of cancer cells in altering T-cell transcriptomes. Profiling of a primary tumour and two matched lymph nodes provided evidence that KLK3 ectopic expression is associated with micrometastases. Close cell-cell communication exists among cells. We identified an endothelial subset harbouring active communication (activated endothelial cells, aECs) with tumour cells. Together with sequencing of an additional 11 samples, we showed that aECs are enriched in castration-resistant prostate cancer and promote cancer cell invasion. Finally, we created a user-friendly web interface for users to explore the sequenced data.

Purpose: Limbal niche cells (LNCs) play a vital role in the maintenance of limbal epithelial stem/progenitor cells (LESCs). Four methods have been reported to isolate and expand LNCs: digestion by collagenase alone (C-LNC), collagenase following dispase removal of the limbal epithelium (DC-LNC), dissection of dispase-isolated limbal epithelial sheets (D-LNC), and explant cultures of limbal stromal tissues (Ex-LNC). This study aimed to isolate LNCs using those four methods and to compare their capacity to maintain LESCs., Methods: LNCs were isolated from the rat corneal limbus by the following methods: C-LNC, DC-LNC, D-LNC, and Ex-LNC. Quantitative real-time PCR and immunofluorescence staining were used to analyze the expression of embryonic stem cell (ESC) markers. The ability to maintain LESCs was assessed on the basis of colony-forming capacity and the expression of progenitor, proliferation, and differentiation markers in three-dimensional (3D) Matrigel and Transwell systems. Notch signaling of LESCs supported by different LNCs in Transwell inserts was analyzed by quantitative real-time PCR., Results: DC-LNCs exhibited lower expression of CK12 during isolation and expansion. Among P4-expanded LNCs, DC-LNCs expressed significantly higher levels of Sox2, Oct4, Nanog, and N-cadherin than C-LNCs, D-LNCs, and Ex-LNCs. Compared with other LNCs, DC-LNCs were more effective in maintaining LESCs with higher holoclone-forming efficiency, greater expression of ΔNp63α and Ki67, and lower expression of CK12. DC-LNCs were also more capable of downregulating Notch signaling of LESCs., Conclusions: DC-LNCs were more effective in expressing ESC markers and maintaining LESCs compared to other LNCs. This study identifies an optimal method for the isolation of LNCs in tissue engineering and ocular surface reconstruction.

Introduction: Patients with locally advanced prostate cancer are at high risk of recurrence after definitive treatment. There are emerging data that radical prostatectomy can delay the progression of castration resistance and potentially prolong survival. Neoadjuvant radiation therapy improves local control and has shown survival benefit with favourable toxicity profiles in several other malignancies. We have designed this trial to investigate whether this combination, which theoretically maximises local control, is a safe and feasible approach for treating locally advanced prostate cancer., Methods and Analysis: This study is a phase I, open-label study to investigate the safety and feasibility of neoadjuvant hormone and radiation therapy followed by robot-assisted radical prostatectomy by a traditional 3+3 dose-escalation design with four planned radiation dose levels (39.6 Gy/22F, 45 Gy/25F, 50.4 Gy/28F and 54 Gy/30F). Locally advanced prostate cancer patients with positive pelvic and/or retroperitoneal lymph nodes will be recruited. The primary objective is to determine the adverse events and maximal tolerable dose (MTD) of neoadjuvant radiotherapy. Toxicity will be assessed using the National Cancer Institute Common Toxicity Criteria V.5.0., Ethics and Dissemination: This protocol was approved by the Institutional Review Board of Shanghai Changhai Hospital (ref. CHEC2019-070 and CHEC2019-082). The study will be performed in compliance with applicable local legislation and in accordance with the ethical principles developed by the World Medical Association in the Declaration of Helsinki 2013. Study results will be disseminated through conferences and peer-reviewed scientific journals., Trial Registration Numbers: ChiCTR1900022716; ChiCTR1900022754., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Zinnia elegans L., known as common zinnia, is an annual flowering plant belonging to the Asteraceae family and native to North America. The plant has colorful flowers and is one of the popular ornamental bedding plants for gardening. In March 2020, powdery mildew symptoms were observed in a zinnia floral field with an incidence of >70% in Dacun Township, Changhua County, Taiwan. The symptoms were spotted on the stems, flower petals and leaves which appeared as irregular colonies and white patches on the surfaces. When disease progressed, most of the plant surfaces were covered by the white fungal colonies and became yellowish. Under microscopic examination, hyphal appressoria of the fungus were indistinct or slightly nipple-shaped. The conidiophores were unbranched, erect, straight, smooth to slightly rough, 75.0 to 200.0 × 10.0 to 15.0 µm (n=10), composed of a cylindrical, flexuous foot cell, 40.0 to 100.0 × 8.8 to 15.0 µm (n=10), and following 1 to 5 shorter cells. The conidia were ellipsoid to ovoid, 25.0 to 37.5 × 15.0 to 23.8 µm (n=60), with an average length-to-width ratio of 1.8 and contained fibrosin bodies. No chasmothecia were found. Three voucher specimens (TNM Nos. F0033680, F0033681, and F0033682) were deposited in the National Museum of Natural Science, Taichung City, Taiwan. To confirm the identification, the internal transcribed spacer (ITS) regions of the three specimens were amplified using primer pairs ITS1/PM6 and PM5/ITS4 (Shen et al. 2015) and sequenced from both ends. The resulting sequences were deposited in GenBank under Accession Nos. MT568609, MT568610, and MT568611. The sequences were identical to each other and shared a 100% identity with that of Podosphaera xanthii MUMH 338 on Z. elegans from Japan (Accession No. AB040355) (Ito and Takamatsu 2010) over a 475 bp alignment. Accordingly, the fungus was identified as P. xanthii (Castagne) U. Braun & Shishkoff (Braun and Cook 2012) based on its morphological and molecular characters. Pathogenicity was demonstrated through inoculation by gently pressing naturally infected leaves onto leaves of three healthy potted common zinnia that had been sprayed with 0.02% Tween 20. Additional three non-inoculated plants treated in the same way without inoculating the powdery mildew served as the controls. Powdery mildew colonies were observed on inoculated leaves after 10 days at room temperature, later the diseased leaves became yellowish and deteriorated. The morphological traits of the fungus on the inoculated leaves were similar to those of the first observed. In addition, the ITS sequence from a colony on the inoculated leaves was 100% identical to MT568609-MT568611, fulfilling the Koch's postulates. All the controls remained symptomless. Z. elegans is known to be a host for different species of powdery mildew in the genus Erysiphe , Golovinomyces , and Podosphaera (Farr and Rossman 2020). In Taiwan, powdery mildew has been briefly reported on zinnia without detailed descriptions (Hsieh 1983). This study confirmed P. xanthii as a causal agent of powdery mildew in Taiwan and the awareness of the disease may benefit the floral industry. To our knowledge, this is the first confirmed report of P. xanthii on Z. elegans in Taiwan.

Purpose: Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA) 4 based on the integrin α6-targeted RWY peptide that we previously identified to detect HCC., Procedures: Contrast-enhanced MRI was carried out to evaluate the use of RWY-dL-(Gd-DOTA) 4 to detect HCC lesions in subcutaneous and diethylnitrosamine (DEN)-induced HCC mouse models., Results: Enhancement MR signals were observed in HCC-LM3 subcutaneous liver tumors in the first 5 min post-injection of RWY-dL-(Gd-DOTA) 4 at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA) 4 generated superior contrast enhancement for liver tumors in chemical-induced HCC mice. Importantly, RWY-dL-(Gd-DOTA) 4 provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA) 4 showed minimal gadolinium retention in normal tissues and organs at 48 h post-injection., Conclusion: These findings potentiate the use of RWY-dL-(Gd-DOTA) 4 for the MRI of HCC to improve the diagnosis of HCC.

A simple and practical method for the synthesis of phosphoryl-substituted indolo[2,1-a]isoquinolin-6(5H)-ones and benzimidazo[2,1-a]isoquinolin-6(5H)-ones through manganese(iii)-promoted tandem phosphinoylation/cyclization of 2-arylindoles or 2-arylbenzimidazoles with disubstituted phosphine oxides was developed. In this transformation, new C-P bond and C-C bond were constructed simultaneously under silver-free conditions, exhibiting a broad substrate scope. It was noted that not only diarylphosphine oxides but also dialkyl and arylalkyl-phosphine oxides were compatible with the conditions.

Objective: To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)., Patients and Methods: We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression., Results: We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Most of our comparisons included short-term follow-up information. The median age of the participants was 38 years. Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies. We found low- to very low-quality evidence that α-blockers may reduce prostatitis symptoms based on a reduction in National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) scores of >2 (but <8) with an increased incidence of minor adverse events such as dizziness and hypotension. Moderate- to low-quality evidence indicates that 5α-reductase inhibitors, antibiotics, anti-inflammatories, and phytotherapy probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. Intraprostatic botulinum toxin A (BTA) injection may cause a large reduction in prostatitis symptoms with procedure-related adverse events (haematuria), but pelvic floor muscle BTA injection may not have the same effects (low-quality evidence). Allopurinol may also be ineffective for reducing prostatitis symptoms (low-quality evidence). We assessed a wide range of interventions involving traditional Chinese medicine; low-quality evidence showed they may reduce prostatitis symptoms without an increased incidence in adverse events. Moderate- to high-quality evidence indicates that the following interventions may be ineffective for the reduction of prostatitis symptoms: anticholinergics, Escherichia coli lysate (OM-89), pentosan, and pregabalin. Low- to very low-quality evidence indicates that antidepressants and tanezumab may be ineffective for the reduction of prostatitis symptoms. Low-quality evidence indicates that mepartricin and phosphodiesterase inhibitors may reduce prostatitis symptoms, without an increased incidence in adverse events., Conclusions: Based on the findings of low- to very low-quality evidence, this review found that some pharmacological interventions such as α-blockers may reduce prostatitis symptoms with an increased incidence of minor adverse events such as dizziness and hypotension. Other interventions may cause a reduction in prostatitis symptoms without an increased incidence of adverse events while others were found to be ineffective., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

A copper-catalyzed C-H [3 + 2] annulation of N-substituted anilines with α-carbonyl alkyl bromides for the synthesis of 3,3'-disubstituted oxindoles is developed. Tandem C-H cycloamidation reactions of various α-carbonyl alkyl bromide derivatives including tertiary-α-bromoalkyl ketone esters, malonic esters and cycloalkanes, with N-aryl or alkyl substituted anilines, can be performed using this system, affording a vast array of valuable 3,3'-disubstituted oxindoles in moderate to good yields.

Purpose: To examine whether submucosal saline injection (SSI) can improve traditional endoscopic ultrasound (EUS) accuracy in distinguishing between T1a and T1b stage esophageal squamous cell carcinoma (ESCC)., Experimental Design: Patients with T1N0M0 stage ESCC ( n = 180) ages 18 to 85 years were enrolled between February 14, 2012 to June 4, 2018 at Sun Yat-sen University Cancer Center (Guangdong, China). They were randomly assigned (1:1) to receive either EUS examination after 3-5 mL SSI or EUS only examination. All the patients were referred to thoracic surgeons to receive endoscopic resection (ER) or esophagectomy 5 to 10 days after EUS examination. Standard EUS criteria were used to preoperatively stage the ESCC cases, and surgical pathology reports after referral were used to postoperatively stage the cases. The primary endpoint was the diagnostic accuracy of T1b staging [defined as the sum of the true positive (T1b) and true negative (T1a) cases divided by the total number of cases]., Results: Among the per-protocol population, the SSI+EUS group ( n = 81) was superior to the EUS-only group ( n = 85) in terms of the diagnostic accuracy for T1b staging [93.8% (95% confidence interval (CI), 88.6-99.1) vs. 65.9% (95% CI, 55.8-76.0); P < 0.001]. The positive predictive value of SSI+EUS for diagnosing T1b ESCC reached 90.9% (95% CI, 81.1-100), which was significantly superior to that of EUS only [0.576 (0.450-0.702), P = 0.001]., Conclusions: SSI significantly improves the diagnostic accuracy of EUS in distinguishing between T1a and T1b ESCC, which might help avoid unnecessary esophagectomy and diagnostic ER., (©2019 American Association for Cancer Research.)

Purpose: To investigate the feasibility and surgical technique of robotic perineal radical prostatectomy (RPRP)., Materials and Methods: We retrospectively analyzed 6 consecutive patients diagnosed with prostate cancer from December 2018 to May 2019 who underwent RPRP at our center. Perioperative outcomes were recorded for safety and feasibility analysis., Results: Six patients successfully underwent RPRP with no conversion to open procedures. Operative time was 140 (interquartile range [IQR] 123.75-148.75) min, console time was 70 (IQR 62.5-70) min, with an estimated blood loss of 125 (IQR 100-187.5) mL. Patients were discharged 2 days postoperatively (IQR range 1-3) with pelvic drainages removed. The Foley catheter was removed 2 weeks after surgery. Postoperative pathology revealed 5 patients with locally advanced disease (apical margin-positive prostate cancer [pT3a]bNx). Two patients had a positive surgical margin (33.3%). No complications of Clavien grade 3 and above were recorded; 1 patient had a delay in wound-healing of 1 week. Postoperative continence was achieved for 2 patients immediately after Foley catheter removal, 2 recovered 1-month postoperatively, and 1 recovered within 3 months, and 1 still had mild incontinence at the latest follow-up 1-month postoperatively., Conclusion: RPRP is a safe and feasible alternative for the transperitoneal route in selected patients. Further investigation is required to assess its oncological and quality-of-life results., (© 2020 S. Karger AG, Basel.)

The differences in the mechanism of cadmium (Cd) accumulation in the grains of different wheat (Triticum aestivum L.) cultivars remain unclear. Thus, we conducted a hydroponic experiment in a greenhouse to compare root surface adsorption, root uptake, subcellular distribution, and chemical forms of Cd between low- and high-Cd-accumulating wheat cultivars at seedling stage, to improve our understanding of the differences between cultivars. The results showed that Cd adsorbed on the root surface was mainly in a complexed form, and the total amount of Cd on the Yaomai16 (YM, high-Cd-accumulating genotypes) root surface was higher (p < 0.05) than that on Xinmai9817 (XM, low-Cd-accumulating genotypes). A large amount of Cd ions adsorbed on root surface would cause plant damage and inhibit growth. Comparing the root-to-shoot translocation factors of Cd, the transfer coefficients of YM were 1.017, 1.446, 1.464, and 1.030 times higher than those of XM under 5, 10, 50, and 100 μmol L -1 Cd treatments, respectively. The subcellular distribution of Cd under Cd exposure is mainly in the cell wall and soluble fraction. The proportions of Cd in YM shoot soluble fraction were higher than those in XM, which was the main detoxification mechanism limiting the activity of Cd and may be responsible for low Cd accumulation in grains, while the effects of the chemical forms of Cd on migration and detoxification were not found to be related to Cd accumulation in the kernels.

Helicoverpa armigera, cotton bollworm, is one of the most disastrous pests worldwide, threatening various food and economic crops. Functional genomic tools may provide efficient approaches for its management. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, dependent on a single guide RNA (sgRNA), has been used to induce indels for targeted mutagenesis in cotton bollworm. However, genomic deletions may be more desirable to disrupt the function of noncoding genes or regulatory sequences. By injecting two sgRNAs with Cas9 protein targeting different exons, we obtained predictable genomic deletions of several hundred bases. We achieved this type of modification with different combinations of sgRNA pairs, including HaCad and HaABCC2. Our finding indicated that CRISPR/Cas9 can be used as an efficient tool to engineer genomes with chromosomal deletion in H. armigera., (© 2018 Institute of Zoology, Chinese Academy of Sciences.)

Brown root rot (BRR), caused by the white rot fungus Phellinus noxius , is an epidemic disease of diverse broadleaved and coniferous tree species in many tropical and subtropical regions. Flooding and trenching control measures are difficult to implement, and chemical controls can have an adverse impact on ecosystems. Previous studies have provided in vitro evidence for the potential use of Trichoderma spp. for biocontrol of BRR. Here, we analyzed the in vitro antagonistic and mycoparasitic abilities of four Trichoderma spp. isolates against four P. noxius isolates in dual culture and Ficus microcarpa wood blocks. A convenient inoculation system based on root inoculation of a highly susceptible loquat ( Eriobotrya japonica ) with P. noxius -colonized wheat-oat grains was developed to examine the effect of Trichoderma treatment in planta. Preventive application of Trichoderma asperellum TA, the isolate showing high antagonistic activity in vitro, was effective in preventing and delaying the wilting of P. noxius -inoculated loquat cuttings in greenhouse trials. To understand the specific niche in which T. asperellum TA interacts with P. noxius , KOH-aniline blue fluorescence microscopy was used to investigate the colonization of loquat roots by P. noxius and/or T. asperellum TA. Dilution plating assays were also conducted to quantify Trichoderma populations in the rhizosphere and potting mix. T. asperellum TA was able to robustly establish in the rhizosphere and potting mix but with scarce root penetration limited to the superficial layer. We discuss the timing and strategy for applying antagonistic Trichodema sp. on living trees or in BRR-infested areas for BRR management.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. We considered a 25% decrease of NIH-CPSI baseline score or a six-point reduction as MCID., Objectives: To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome., Search Methods: We performed a comprehensive search using CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, trial registries, grey literature and conference proceedings, with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019., Selection Criteria: We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions compared to placebo or in head-to-head comparisons., Data Collection and Analysis: Two review authors independently assessed study eligibility, extracted data, and assessed the risks of bias of included studies. We assessed the quality of the evidence (QoE) using the GRADE approach., Main Results: We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Unless stated otherwise, our comparisons were based on short-term follow-up (less than 12 months). Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies.1. Alpha blockers: (24 studies, 2061 participants). We are uncertain about the effects of these drugs on prostatitis symptoms when compared to placebo at short-term follow-up (mean difference (MD) in total NIH-CPSI score -5.01, 95% confidence interval (CI) -7.41 to -2.61; 18 studies, 1524 participants, very low QoE) and at long-term follow-up (MD -5.60, 95% CI -10.89 to -0.32; 4 studies, 235 participants, very low QoE). Alpha blockers may be associated with an increased incidence of adverse events, such as dizziness and postural hypotension (risk ratio (RR) 1.60, 95% CI 1.09 to 2.34; 19 studies, 1588 participants; low QoE). Alpha blockers probably result in little to no difference in sexual dysfunction, quality of life and anxiety and depression (moderate to low QoE).2. 5-alpha reductase inhibitors (5-ARI): (2 studies, 177 participants). Finasteride probably reduces prostatitis symptoms compared to placebo (NIH-CPSI score MD -4.60, 95% CI -5.43 to -3.77; 1 study, 64 participants; moderate QoE) and may not be associated with an increased incidence of adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.3. Antibiotics: (6 studies, 693 participants). Antibiotics (quinolones) may reduce prostatitis symptoms compared to placebo (NIH-CPSI score MD -2.43, 95% CI -4.72 to -0.15; 5 studies, 372 participants; low QoE) and are probably not associated with an increased incidence in adverse events (moderate QoE). Antibiotics probably result in little to no difference in sexual dysfunction and quality of life (moderate QoE). There was no information on anxiety or depression.4. Anti-inflammatories: (7 studies, 585 participants). Anti-inflammatories may reduce prostatitis symptoms compared to placebo (NIH-CPSI scores MD -2.50, 95% CI -3.74 to -1.26; 7 studies, 585 participants; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.5. Phytotherapy: (7 studies, 551 participants). Phytotherapy may reduce prostatitis symptoms compared to placebo (NIH-CPSI scores MD -5.02, 95% CI -6.81 to -3.23; 5 studies, 320 participants; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). Phytotherapy may not improve sexual dysfunction (low QoE). There was no information on quality of life or anxiety and depression.6. Botulinum toxin A (BTA): Intraprostatic BTA injection (1 study, 60 participants) may cause a large reduction in prostatitis symptom (NIH-CPSI scores MD -25.80, 95% CI -30.15 to -21.45), whereas pelvic floor muscle BTA injection (1 study, 29 participants) may not reduce prostatitis symptoms (low QoE). Both comparisons used a placebo injection. These interventions may not be associated with an increased incidence in adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.7. Allopurinol: (2 studies, 110 participants). Allopurinol may result in little to no difference in prostatitis symptoms and adverse events when compared to placebo (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.8. Traditional Chinese medicine (TCM): (7 studies, 835 participants); TCM may reduce prostatitis symptoms (NIH-CPSI score, MD -3.13, 95% CI -4.99 to -1.28; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). TCM probably does not improve sexual dysfunction (moderate QoE) and may not improve symptoms of anxiety and depression (low QoE). There was no information on quality of life.The most frequent reasons for downgrading the QoE were study limitations, inconsistency and imprecision. We found few trials with active comparators., Authors' Conclusions: We found low- to very low-quality evidence that alpha blockers, antibiotics, 5-ARI, anti-inflammatories, phytotherapy, intraprostatic BTA injection, and traditional Chinese medicine may cause a reduction in prostatitis symptoms without an increased incidence of adverse events in the short term, except for alpha blockers which may be associated with an increase in mild adverse events. We found few trials with active comparators and little evidence of the effects of these drugs on sexual dysfunction, quality of life or anxiety and depression. Future clinical trials should include a full report of their methods, including adequate masking, consistent assessment of all patient-important outcomes, including potential treatment-related adverse events, and appropriate sample sizes.

Integrin α6 emerges to be a diagnostic biomarker for hepatocellular carcinoma (HCC). Here, we translated our previously identified integrin α6 targeted peptide RWY into a positron emission tomography (PET) tracer 18 F-RWY for the detection of HCC lesions in following four HCC mouse models including subcutaneous, orthotopic, genetically engineered and chemical induced HCC mice. 18 F-RWY produced high PET signals in liver tumor tissues that were reduced by blocking studies using nonradiolabeled RWY peptide. We compared the integrin α6 targeted PET tracer 18 F-RWY with the integrin αvβ3-targeted PET tracer 18 F-3PRGD 2 and the clinical PET tracer 18 F-FDG in chemical induced HCC mice. Among 12 HCC identified by enhanced magnetic resonance imaging (MRI) with hepatocellular specific gadoxetate disodium Gd-EOB-DTPA, the sensitivities of 18 F-RWY, 18 F-3PRGD 2 and 18 F-FDG were approximately 92%, 73% and 50% while the tumor-to-liver ratios were 4.36 ± 1.41, 1.97 ± 0.43 and 1.63 ± 0.23 respectively. Additionally, PET imaging with the integrin α6 targeted 18 F-RWY enabled to visualize small HCC lesions with diameters approximately 0.2 cm that was hard to be distinguished from surround hepatic vascular by enhanced MRI with Gd-EOB-DTPA. These findings potentiate the use of integrin α6 targeted PET tracer 18 F-RWY for the detection of HCC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin α6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin α6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics. In this study, we developed a radiotracer, 18 F-RWY, based on this integrin α6-targeted RWY peptide for positron emission tomography (PET) imaging of CRC. Integrin α6 was overexpressed on several CRC cells including HT29 cells where the biotin-labeled RWY peptide colocalized with integrin α6. 18 F-RWY PET imaging was performed on subcutaneous, chemically induced, and genetically engineered CRC mice. 18 F-RWY generated high PET signals in subcutaneous HT29 tumors, and the tumor uptake of 18 F-RWY was reduced by a blocking study using nonradio-labeled RWY. Moreover, 18 F-RWY PET imaging enabled detection of CRC in chemically induced and genetically engineered CRC mice. The overexpression of integrin α6 in tumor tissues isolated from chemically induced and genetically engineered CRC mice was confirmed. These results demonstrate the potential clinical application of 18 F-RWY for PET imaging of CRC., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)