Current Research Status, Opportunities, and Future Challenges of Nine Representative Persistent Herbicides.

Pesticides are extensively utilized in contemporary agriculture to manage pests, enhance crop yields, and sustain productivity. Nevertheless, the persistent herbicide represents a dual-edged weapon. On one hand, their prolonged efficacy enables reduced application frequency during crop growth seasons, resulting in cost savings on labor. However, the presence of these residues within fields poses safety risks to soil quality, sensitive crops in subsequent rotations, agricultural product quality, and the ecological environment. This review presents a comprehensive review on the mechanisms of action, application risks, ecotoxicology, and residue analysis methods of nine representative persistent herbicides (namely, atrazine, imazethapyr, imazapic, mesosulfuron-methyl, halosulfuron-methyl, fomesafen, diflufenican, quinclorac, and pyroxasulfone). The objective is to guide their scientific and rational utilization in agricultural practices while minimizing phytotoxicity risks and effectively monitoring and controlling soil pollution. These can not only provide practical recommendations for mitigating potential plant toxicity and ecological environmental risks but also contribute valuable technical insights for efficient soil pollution monitoring and prevention. Additionally, unaddressed research objectives were also anticipated.

Simplified Electrochemical Approach for End-Point Yet Quantitative Detection of Nucleic Acids in Resource-Limited Settings.

Nucleic acid detection plays a crucial role in various aspects of health care, necessitating accessible and reliable quantification methods, especially in resource-limited settings. This work presents a simplified electrochemical approach for end-point yet quantitative nucleic acid detection. By elevating the concentration of redox species and choosing potential as the signals, we achieved enhanced signal robustness, even in the presence of interfering substances. Leveraging this robustness, we accurately measured pH-induced redox potential changes in methylene blue solution for end-point nucleic acid detection after loop-mediated isothermal amplification (LAMP). Our method demonstrated quantitative detection of the SARS-CoV-2 N gene and human ATCB gene and successful discrimination of the human BRAF V600E mutation, comparable in sensitivity to commercial kits. The developed user-friendly electrochemical method offers a simplified and reliable approach for end-point yet quantitative detection of nucleic acids, potentially expanding the benefits of nucleic acid testing in resource-limited settings.

Autofluorescence imaging-assisted medical thoracoscopy in the diagnosis of malignant pleural disease.

BACKGROUND: Medical thoracoscopy (MT) does not always provide a conclusive diagnosis of pleural diseases because the endoscopic appearance of pleural diseases can be misleading. Autofluorescence imaging (AFI) is an effective assistive diagnostic tool. However, its clinical application for pleural disease remains controversial. OBJECTIVES: This prospective study evaluated the clinical usefulness of AFI-assisted MT for diagnosis of malignant pleural diseases. METHODS: Patients with unexplained pleural effusion admitted to our clinics between December 2018 and September 2021 were enrolled. We performed white-light thoracoscopy (WLT) first, and then AFI, during MT. Images of endoscopic real-time lesions were recorded under both modes. Pleural biopsy specimens were analyzed pathologically. Between-groups differences in diagnostic sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) were assessed using 95% confidence intervals (CI). Receiver operating characteristic curves and decision curve analyses were employed to analyze the diagnostic efficiency of these two modes. RESULTS: Of 126 eligible patients, 73 cases were diagnosed with malignant pleural disease. A total of 1292 biopsy specimens from 492 pleural sites were examined for pathological changes. The diagnostic sensitivity, PPV, and NPV of AFI were 99.7%, 58.2%, and 99.2%, respectively. AFI was significantly superior to WLT, which had a sensitivity of 79.7%, PPV of 50.7%, and NPV of 62.8%. Subgroup analysis showed that the AFI type III pattern was significantly more specific for pleural malignant disease than that of WLT. CONCLUSIONS: AFI could further improve the diagnostic efficacy of MT by providing better visualization, convenience, and safety.

Features of transbronchial lung cryobiopsy-diagnosed fibrotic hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is a common type among all the interstitial lung diseases, and transbronchial lung cryobiopsy is an alternative diagnostic technique for interstitial lung diseases. In this study, we describe the clinical and pathological features of fibrotic hypersensitivity pneumonitis diagnosed with transbronchial lung cryobiopsy (TBLC). METHODS: A total of 46 diffused parenchyma lung disease (DPLD) patients received TBLC were included in this study. Medical records including medical history spirometry examinations, 6-min walk test (6MWT) results, high resolution computed tomographic (HRCT) scans, BAL, and histopathology were collected. Results of HRCT and histopathology were compared and classified, especially. RESULTS: Sixteen patients were diagnosed with fibrotic HP, the mean age of whom was 56.3 ± 12.1 years, and 62.5% of them were male. Three of the 16 patients had been misdiagnosed as tuberculosis and received antituberculosis medications, five patients had been diagnosed as unclassifiable pulmonary fibrosis, and five patients had been diagnosed as idiopathic pulmonary fibrosis (IPF). Thirteen (81.3%) patients had a normal lymphocyte count in BAL. The pathological features of usual interstitial pneumonia (UIP) were detected in 11 (68.8%) of the cases, poor defined granulomatous was detected in nine (56.3%) of the cases, and bronchiolocentric fibrosis was detected in two (12.5%) of the 16 cases. CONCLUSIONS: Fibrotic hypersensitivity pneumonitis should be included in differential diagnosis of pulmonary fibrosis. Pathological characteristics of fibrotic hypersensitivity pneumonitis could be demonstrated from cryobiopsy lung tissue. TBLC is recommended as an alternative diagnostic technique, which may improve the specificity of hypersensitivity pneumonia detection, and UIP is the most frequent pathological finding.

MicroRNA-263b confers imidacloprid resistance in Sitobion miscanthi (Takahashi) by regulating the expression of the nAChRß1 subunit.

The Chinese wheat aphid Sitobion miscanthi (CWA) is an important harmful pest in wheat fields. Imidacloprid plays a critical role in controlling pests with sucking mouthparts. However, imidacloprid-resistant pests have been observed after insecticide overuse. Point mutations and low expression levels of the nicotinic acetylcholine receptor ß1 (nAchRß1) subunit are the main imidacloprid-resistant mechanisms. However, the regulatory mechanism underlying nAChRß1 subunit expression is poorly understood. In this study, a target of miR-263b was isolated from the 5'UTR of the nAchRß1 subunit in the CWA. Low expression levels were found in the imidacloprid-resistant strain CWA. Luciferase reporter assays showed that miR-263b could combine with the 5'UTR of the nAChRß1 subunit and suppress its expression by binding to a site in the CWA. Aphids treated with the miR-263b agomir exhibited a significantly reduced abundance of the nAchRß1 subunit and increased imidacloprid resistance. In contrast, aphids treated with the miR-263b antagomir exhibited significantly increased nAchRß1 subunit abundance and decreased imidacloprid resistance. These results provide a basis for an improved understanding of the posttranscriptional regulatory mechanism of the nAChRß1 subunit and further elucidate the function of miRNAs in regulating susceptibility to imidacloprid in the CWA. These results provide a better understanding of the mechanisms of posttranscriptional regulation of nAChRß1 and will be helpful for further studies on the role of miRNAs in the regulation of nAChRß1 subunit resistance in homopteran pests.

Mechanism of Pydiflumetofen Resistance in Fusarium graminearum in China.

Fusarium head blight (FHB), which is primarily caused by Fusarium graminearum, is a widespread and devastating disease of wheat. In the absence of resistant varieties, the control of FHB relies heavily on the application of fungicides, and the new generation SDHI fungicide, pydiflumetofen, has recently been registered in China for the control of FHB in wheat. The current study explored three genetically stable, highly resistant laboratory mutants (S2-4-2R, S27-3R, and S28-2R, with EC50 values of 25.10, 28.57, and 19.22 µg/mL, respectively) to investigate the potential risks associated with pydiflumetofen resistance. Although the mycelial growth of the mutants differed little compared to their parental isolates, the study found that the resistant mutants exhibited significantly reduced (p < 0.05) levels of sporulation and pathogenicity, which suggests a significant fitness cost associated with pydiflumetofen resistance in F. graminearum. Sequence analysis of the Sdh target protein identified numerous amino acid substitutions in the predicted sequences of the four subunits: FgSdhA, FgSdhB, FgSdhC, and FgSdhD. Indeed, the mutants were found to have a series of substitution in multiple subunits such that all three exhibited five identical changes, including Y182F in the FgSdhA subunit; H53Q, C90S, and A94V in FgSdhB; and S31F in FgSdhC. In addition, gene expression analysis revealed that all of the FgSdh genes had significantly altered expression (p < 0.05), particularly FgSdhA and FgdhC, which exhibited remarkably low levels of expression. However, the study found no evidence of cross-resistance between pydiflumetofen and tebuconazole, fludioxonil, prochloraz, fluazinam, carbendazim, pyraclostrobin, or difenoconazole, which indicates that these fungicides, either in rotation or combination with pydiflumetofen, could mitigate the risk of resistance emerging and provide ongoing control of FHB to ensure high and stable wheat yields.

An update of the long-term outcome of patients with nonspecific pleurisy at medical thoracoscopy.

BACKGROUND: Medical thoracoscopy (MT) is recommended in patients with undiagnosed exudative pleural effusion and offers a degree of diagnostic sensitivity for pleural malignancy. However, not all patients who undergo MT receive an exact diagnosis. Our previous investigation from 2014 summarized the long-term outcomes of these patients with nonspecific pleurisy (NSP); now, we offer updated data with the goal of refining our conclusions. METHODS: Between July 2005 and August 2018, MT with pleural biopsies were performed in a total of 1,254 patients with undiagnosed pleural effusions. One hundred fifty-four patients diagnosed with NSP with available follow-up data were included in the present study, and their medical records were reviewed. RESULTS: A total of 154 patients were included in this study with a mean follow-up duration of 61.5 ± 43.7 months (range: 1-180 months). No specific diagnosis was established in 67 (43.5%) of the patients. Nineteen patients (12.3%) were subsequently diagnosed with pleural malignancies. Sixty-eight patients (44.2%) were diagnosed with benign diseases. Findings of pleural nodules or plaques during MT and the recurrence of pleural effusion were associated with malignant disease. CONCLUSIONS: Although most NSP patients received a diagnosis of a benign disease, malignant disease was still a possibility, especially in those patients with nodules or plaques as noted on the MT and a recurrence of pleural effusion. One year of clinical follow-up for NSP patients is likely sufficient. These updated results further confirm our previous study's conclusions.

Functional Analysis of SlGSTE12 in Pyrethroid and Organophosphate Resistance in Spodoptera litura.

Glutathione S-transferase genes in the epsilon group were reported to function in insecticide resistance. SlGSTE12 was validated to be overexpressed in pyrethroid- and organophosphate-resistant populations of Spodoptera litura compared to a susceptible population. A functional study of heterologously expressed SlGSTE12 showed that Km and Vmax for 1-chloro-2,4-dinitrobenzene (CDNB) conjugating activity were 0.70 ± 0.18 mmol L-1 and 90.6 ± 9.4 nmol mg-1 min-1, respectively. ß-Cypermethrin and cyhalothrin showed much weaker inhibition of SlGSTE12 activity to CDNB conjugation than fenvalerate, chlorpyrifos, and phoxim. Ultrahigh-performance liquid chromatography analysis showed that SlGSTE12 had significant metabolism activity to fenvalerate and phoxim both in vitro and in Escherichia coli, especially to chlorpyrifos, and slight metabolism activity toward cyhalothrin only in vitro. Silencing of SlGSTE12 by RNAi increased the mortality to fenvalerate, cyhalothrin, and chlorpyrifos significantly. SlGSTE12 also had a significant antioxidant ability against cumene hydroperoxide. Our study suggested that SlGSTE12 could metabolize phoxim, fenvalerate, cyhalothrin, and especially chlorpyrifos. SlGSTE12 might also participate in pyrethroid and organophosphate resistance by antioxidant activity.

From biomineralization to tumorogenesis-the expanding insight of the physiological and pathological roles of Fam20C.

Fam20C is a Golgi kinase phosphorylating the majority of the secreted proteins. In this decade, the function of Fam20C has been largely disclosed in the loss-of function models. How the influence of the overexpressed Fam20C on cells or organs, and whether Fam20C was associated with tumorogensis still remain unknown. In the latest article in Bioscience Reports, a group from The Second Affiliated Hospital of Harbin Medical University established a correlation between the elevated Fam20C expression and the poor prognosis of multiple cancers (Biosci. Rep. (2021), 41(1) BSR20201920). In addition, they also proposed the potential mechanisms how the increased Fam20C expression played a detrimental role in tumor progression by suggesting that the up-regulated Fam20C level affected the infiltration of immune cells and the capability of cancer metastasis. To give an overview of the expanding knowledge of Fam20C involved in the physiological and pathological events, we first reviewed the history of Fam20C study in this commentary, then, evaluated the correlation of the elevated Fam20C expression to the prognosis of multiple cancers, and finally, interpreted the perspectives that the Fam20C gain-of-function model was also critical for cancer therapy.

The electronic and magnetic properties of h-BN/MoS2 heterostructures intercalated with 3d transition metal atoms.

We performed density functional theory calculations to investigate the electronic and magnetic properties of h-BN/MoS2 heterostructures intercalated with 3d transition-metal (TM) atoms, including V, Cr, Mn, Fe, Co, and Ni atoms. It was found that metal and magnetic semiconductor characteristics are induced in the h-BN/MoS2 heterostructures after intercalating TMs. In addition, the results demonstrate that h-BN sheets could promote charge transfer between the TMs and the heterogeneous structure. Specifically, the h-BN/MoS2 heterostructure transforms from an indirect semiconductor to a metal after intercalating V or Cr atoms in the interlayers. For Mn, Fe, and Co atoms, the bandgaps of the intercalated heterojunction systems become smaller when the spin polarization is 100% at the highest occupied molecular orbital level. However, the system intercalated with Ni atoms exhibits no spin polarization and non-magnetic character. Strong covalent-bonding interactions emerged between the intercalated TMs and the nearest S atom of the h-BN/MoS2 heterostructure. In addition, the magnetic moments of the TM atoms show a decreasing trend for all the interstitial intercalated heterostructures compared with their free-standing states. These results reveal that h-BN/MoS2 heterostructures with intercalated TMs are promising candidates for application in multifarious spintronic devices.

Chronic Resistance Exercise Improves Functioning and Reduces Toll-Like Receptor Signaling in Elderly Patients With Postoperative Deconditioning.

OBJECTIVE: Elderly patients continue to experience low levels of mobility during and following postoperative hospitalization that lead to persistent physical decline. Therefore, here we compared chronic resistance (CR) exercise against chronic aerobic (CA) exercise in ameliorating postoperative functioning and reducing proinflammatory muscular Toll-like receptor (TLR)-associated signaling in elderly postoperative patients. METHODS: We conducted a prospective, randomized trial comparing the effects of 3 exercise programs (CR, CA, and CR + CA) in 66 elderly patients recovering from recent hip, femur, or pelvic fracture repair surgery. The primary outcomes were changes in anatomic/physical performance parameters (ie, maximal oxygen intake, endurance, quadriceps cross-sectional area, and maximum knee-extensor force). The secondary outcomes were changes in TLR/nuclear factor kappa beta signaling pathway marker expression. RESULTS: Three of the 4 anatomic/physical performance parameters significantly improved for the CR and CR + CA cohorts. Muscular expression of myeloid differentiation primary response gene 88, transforming growth factor beta-activated kinase 1 (TLR signaling pathway markers), p50, p65, tumor necrosis factor α, and interleukin 6 (nuclear factor kappa beta signaling pathway markers) all showed significant reductions after CR and CR + CA. Serum expression of 2 key TLR4 ligands, heat shock protein 70 and serum amyloid A, also showed significant reductions after CR and CR + CA. CONCLUSIONS: Three months of CR or CR + CA improves maximal oxygen consumption, quadriceps cross-sectional area, and maximum knee-extensor force while lowering muscular proinflammatory signaling markers in elderly adults with postoperative deconditioning.

Prevalence and risk factors on age-related cataract and surgery in adults over 50 years old in Binhu District, Wuxi, China.

AIM: To investigate the prevalence and risk factors of age-related cataract (ARC), ARC surgery procedures, and postoperative vision results among adults over 50 years old in the Binhu District of Wuxi City, China. METHODS: Thirty basic sampling units were analyzed via a cluster random sampling method. Detailed medical histories were collected and eye examinations were performed. Cataract prevalence and surgical procedures were quantified. RESULTS: Among the 6150 participants, 1421 cataract cases were diagnosed and prevalence was 23.1%. The prevalence of cortical, nuclear, and posterior subcapsular cataracts increased with age (P<0.001). Cataract prevalence was significantly higher among elderly, female, or illiterate individuals and people with hypertension, diabetes, and a history of smoking and drinking (all P<0.05). As participant age increased and education level decreased, the frequency of cataract blindness surgeries gradually decreased, but without statistical significance within groups (P>0.05). The odds ratio of cataract patients who had or did not have cataract surgery was 3.15 (87/28) and the frequency of cataract blindness surgery was 75.7% (87/115). Poor visual outcomes was in 107 eyes (40.7%) after cataract surgery. Poor vision was mostly caused by uncorrected reflective errors (30.9%) and ocular comorbidities (41.1%). The prevalence of cataract surgery complications was 5.7% (15/263). Surgical complications and posterior capsular opacification were avoidable factors facilitating poor vision. CONCLUSION: ARC, especially in females and illiterate individuals, presents a public health problem in this district. Poor visual outcomes after cataract surgery are frequent. High-quality cataract surgeries and treatment of ocular comorbidities are vital.

Diagnostic value of soluble mesothelin-related peptides in pleural effusion for malignant pleural mesothelioma: An updated meta-analysis.

BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a widely studied tumor marker for diagnosing malignant pleural mesothelioma (MPM). This study discussed the diagnostic value of SMRPs in pleural effusion (PE) for MPM. METHODS: Medline, Embase, Web of Science, and Cochrane library system were systematically searched on the data of SMRPs in PE for MPM diagnosis. Pooled diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve were calculated. RESULTS: Thirteen studies fulfilled the inclusion criteria and a total of 3359 cases including 759 MPM cases, 1061 non-MM (malignant mesothelioma) malignant PE, and 1539 benign PE were brought into this meta-analysis. The pooled results of SMRPs in PE for diagnosing MPM were as follows: sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.68 (95% confidence interval [CI]: 0.64-0.72), 0.91 (95% CI: 0.86-0.94), 7.8 (95% CI: 5.0-12.0), 0.35 (95% CI: 0.31-0.40), and 22 (95% CI: 14-35), respectively. The area under the summary receiver operating characteristic curves (AUC) was 0.75 (95% CI: 0.72-0.80). Subgroup analyzes revealed that the AUC of cohort group using histological diagnosis could be improved to 0.86 (95% CI: 0.83, 0.89). The Deek's funnel plot asymmetry test showed no publication bias. CONCLUSION: Although the sensitivity of SMRPs was low, PE-SMRPs can be a good indicator of the existence of MPM.

Clinical Efficacy of Ciliary Ring Incision Combined with Modified Partial Pars Plana Vitrectomy for Malignant Glaucoma.

BACKGROUND Currently, safe and effective surgical treatment of malignant glaucoma is still under investigation. This study evaluated the clinical efficacy of ciliary ring incision combined with modified partial pars plana vitrectomy in the treatment of malignant glaucoma. The technique is particularly useful in the treatment of "phakic" patients with malignant glaucoma, especially those who wish to preserve the natural lens. MATERIAL AND METHODS We retrospectively analyzed 13 cases (16 eyes) of malignant glaucoma in which patients underwent ciliary ring incision combined with modified partial pars plana vitrectomy based on follow-up data collected from May 2004 to March 2017. The data we analyzed included postoperative best-corrected visual acuity(BCVA), intraocular pressure (IOP), anterior chamber depth (ACD), optic cup changes, and surgical complications; some patients underwent visual field tracking. The mean follow-up period was 33.1±10.6 (range, 19-46) months. RESULTS A statistically significant number of eyes had improved visual acuity 1 year after surgery compared with the preoperative difference (Z=-3.853, P=0.000). Increases in the mean anterior chamber depth and decreases in the mean IOP measured at the 1-week and the 1-year follow-ups were also statistically significant. There were no serious complications during the follow-up period. CONCLUSIONS Ciliary ring incision combined with modified partial pars plana vitrectomy for malignant glaucoma not only provided a clear and reliable intraoperative vitrectomy channel, but it also caused less disturbance of intraocular tissue structure and fewer complications. It also has the advantage of preserving the lens and avoiding further damage to the anatomy in the anterior segment of the eye.

Transition metal atoms absorbed on MoS2/h-BN heterostructure: stable geometries, band structures and magnetic properties.

We have studied the stable geometries, band structures and magnetic properties of transition-metal (V, Cr, Mn, Fe, Co and Ni) atoms absorbed on MoS2/h-BN heterostructure systems by first-principles calculations. By comparing the adsorption energies, we find that the adsorbed transition metal (TM) atoms prefer to stay on the top of Mo atoms. The results of the band structure without spin-orbit coupling (SOC) interaction indicate that the Cr-absorbed systems behave in a similar manner to metals, and the Co-absorbed system exhibits a half-metallic state. We also deduce that the V-, Mn-, Fe-absorbed systems are semiconductors with 100% spin polarization at the HOMO level. The Ni-absorbed system is a nonmagnetic semiconductor. In contrast, the Co-absorbed system exhibits metallic state, and the bandgap of V-absorbed system decreases slightly according to the SOC calculations. In addition, the magnetic moments of all the six TM atoms absorbed on the MoS2/h-BN heterostructure systems decrease when compared with those of their free-standing states.

Prevalence and Causes of Visual Impairment in Adults in Binhu District, Wuxi, China.

BACKGROUND Previously reported data has guided the treatment and prevention of blindness. This study aimed to evaluate the current prevalence and causes of visual impairment among adults who were 50 years old and older in the Binhu District of Wuxi City, China. MATERIAL AND METHODS A randomized sample of stratified clusters was used to analyze individuals from 30 basic sampling units in Wuxi Binhu District. Visual impairment was defined according to World Health Organization (WHO) standards. RESULTS A total of 6725 people who were at least 50 years old participated in this study. According to WHO standards, bilateral low vision and blindness prevalence were both higher in women than in men (low vision: 6.5% vs. 5.2%; and blindness: 1.4% vs. 0.8%; P=0.022 and P=0.039, respectively). The incidence of bilateral visual impairment increased significantly with age (P<0.001 and P<0.001, respectively). Further studies showed that the main causes of bilateral low vision were cataract, high myopic macular degeneration (MMD), and age-related macular degeneration (AMD). The main causes of bilateral blindness were cataract, MMD, and eye loss/atrophy, while the main causes of monocular low vision were cataract, MD, and AMD. The main causes of monocular blindness were cataract, eye loss/atrophy, and AMD. CONCLUSIONS The prevalence of low vision and blindness remains high in the Binhu District of Wuxi City in China, especially among older women. In our study, cataracts were the leading cause of visual impairment. Our study highlights that some efforts should be initiated to prevent and treat blindness and low vision. Additional causes of visual impairment were MMD, AMD, and eye loss/atrophy.

Diagnostic value of medical thoracoscopy in malignant pleural effusion.

BACKGROUND: Medical thoracoscopy has been shown to be an efficacious procedure in diagnosing unexplained exudative pleural effusions with excellent safety. This study aimed to assess the diagnostic significance of thoracoscopy in the management of patients with malignant pleural effusion (MPE). METHODS: Consecutive patients with malignant pleural effusion were retrospectively reviewed, and their demographic, radiographic, thoracoscopic and histological data were collected. RESULTS: Between July 2005 and June 2014, 342 of 833 patients undergoing thoracoscopy were finally confirmed to suffer from MPE. The top three frequent causes of MPE were metastatic carcinoma (79.5%), malignant mesothelioma (10.2%), and lymphoma (2.9%). Among metastatic malignancies, the most common cancer was lung cancer (85.2%), followed by breast cancer (4.4%), ovarian cancer (2.2%), pancreatic cancer (1.8%), etc. No serious adverse events associated with thoracoscopy were recorded. CONCLUSIONS: Medical thoracoscopy is a valuable and safe tool in diagnosing malignant pleural effusion with minimal complication rates.

Microbial Natural Product Alternariol 5-O-Methyl Ether Inhibits HIV-1 Integration by Blocking Nuclear Import of the Pre-Integration Complex.

While Highly Active Antiretroviral Therapy (HAART) has significantly decreased the mortality of human immunodeficiency virus (HIV)-infected patients, emerging drug resistance to approved HIV-1 integrase inhibitors highlights the need to develop new antivirals with novel mechanisms of action. In this study, we screened a library of microbial natural compounds from endophytic fungus Colletotrichum sp. and identified alternariol 5-O-methyl ether (AME) as a compound that inhibits HIV-1 pre-integration steps. Time-of addition analysis, quantitative real-time PCR, confocal microscopy, and WT viral replication assay were used to elucidate the mechanism. As opposed to the approved integrase inhibitor Raltegravir, AME reduced both the integrated viral DNA and the 2-long terminal repeat (2-LTR) circular DNA, which suggests that AME impairs the nuclear import of viral DNA. Further confocal microscopy studies showed that AME specifically blocks the nuclear import of HIV-1 integrase and pre-integration complex without any adverse effects on the importin α/ß and importin ß-mediated nuclear import pathway in general. Importantly, AME inhibited Raltegravir-resistant HIV-1 strains and exhibited a broad anti-HIV-1 activity in diverse cell lines. These data collectively demonstrate the potential of AME for further development into a new HIV inhibitor, and suggest the utility of viral DNA nuclear import as a target for anti-HIV drug discovery.

Long-term outcome of patients with nonspecific pleurisy at medical thoracoscopy.

BACKGROUND: Medical thoracoscopy is an effective and safe procedure for diagnosing pleural effusions of undetermined causes. But there are still a part of patients with pleural effusions were diagnosed as nonspecific pleurisy when no specific biopsy results were found after undergoing thoracoscopic biopsy. The long-term outcome of these patients is unclear, and anxieties about undiagnosed malignancy persist. METHODS: Between July 2005 and June 2014, medical thoracoscopy using the semi-rigid instrument was performed and pleural biopsy was taken in 833 patients with pleural effusions. Fifty-two patients diagnosed with nonspecific pleurisy with available follow-up data were included in the present study and their medical records were reviewed. RESULTS: Fifty-two patients (31 men and 21 women) were included. Mean follow up was 35.5 ± 40.9 months (range, 1-143 months). No specific diagnosis was established in 21 (40.4%) of the patients. Eight of 52 patients with nonspecific pleurisy (15.4%) were subsequently diagnosed with pleural malignancies. 23 of 52 patients (44.2%) were diagnosed as benign diseases. The recurrence of pleural effusion during followed-up and pleural nodules or plaques found in medical thoracoscopy was associated with malignant disease. CONCLUSION: Patients with nonspecific pleurisy after medical thoracoscopy should be closely monitored, especially in those patients with the recurrence of pleural effusion during followed-up, pleural nodules or plaques found in medical thoracoscopy. One year of clinical follow-up for patients found to have nonspecific pleurisy is likely sufficient.