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Li-Juan Hu,1 Zhong Mei,1,2 Yan-Ping Shen,1 Hao-Tian Sun,1 Zhi-Min Sheng,1 Xin-Zhong Chen,1 Xiao-Wei Qian1 1Department of Anesthesiology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Anesthesiology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, People’s Republic of ChinaCorrespondence: Xiao-Wei Qian, Department of Anesthesiology, Women’s Hospital, Zhejiang University School of Medicine, Xueshi Road 1, Hangzhou, 310006, People’s Republic of China, Tel +86-571-87061501, Fax +86 571 87061878, Email qianxw@zju.edu.cnBackground: It is well-known that severe preeclamptic parturients have less vasopressor requirements than normotensive parturients; however, the exact dose difference is poorly documented. This study aimed to determine and compare the ED50 and ED90 of a single bolus phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients with severe preeclampsia and parturients with normotension.Methods: Seventy-five parturients with severe preeclampsia scheduled for cesarean delivery under combined spinal-epidural anesthesia were enrolled and randomly allocated to receive a single bolus of phenylephrine at five different doses (40, 50, 60, 70, and 80 μg), whereas 75 parturients with normotension were randomized to receive a single bolus of phenylephrine at five different doses (70, 80, 90, 100, and 110 μg) for the treatment of the first episode of hypotension. Phenylephrine dose values were log-transformed, the proportions of the successful interventions at each dose were converted to probits, and regression analysis was performed.Results: The ED50 and ED90 (95% CI) of bolus phenylephrine were 72.1 (61.7 to 79.9) μg and 107 (95.9– 128.6) μg in parturients with normotension. The ED50 and ED90 values in parturients with severe preeclampsia were 47.6 (41.3– 52.7) μg and 70.7 (62.9– 86.7) μg. The relative median potency was 1.51 (1.16– 2.61).Conclusion: Under this study conditions, severe preeclamptic parturients required a 34% reduction of ED50 of phenylephrine dose compared with normotensive parturients.Keywords: cesarean delivery, spinal anesthesia, hypotension, phenylephrine, preeclampsia

Sheng Chen,1,* Jin-Jun Wang,2,* Qin-Qin Wang,1 Jun-Wei Hu,1 Shuang Dong,1 Li-Juan Hu,1 Yi-Cheng Jian,1 Xin-Yan Liu,2 Gen-Mei Yang,2 Wu-Jun Xiong1 1Department of Hepatology, Tongji University School of Medicine, Shanghai East Hospital, 2Department of Gerontology, Shanghai Traditional Chinese Medicine University, Shanghai Putuo Central Hospital, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: Several randomized controlled clinical trials have been conducted to investigate the role of carvedilol and propranolol on the effect of portal pressure in patients with cirrhosis, leading to controversial results. Current meta-analysis was performed to compare the efficacy of the two drugs on portal pressure.Patients and methods: Two-hundred and ninety eligible patients were recruited. Published studies were selected based on PubMed, the Cochrane Library, Chinese Journal Full-text Database, and Wanfang Database. The outcome measurements included the mean difference (MD) in the percentage of hepatic vein pressure gradient reduction (%HVPG reduction), the risk ratio (RR) of nonresponders in hemodynamic assessment, and the percentage of mean arterial pressure reduction (%MAP reduction). Subgroup analysis was performed.Results: Seven trials were identified (including five acute and three long-term drug administration randomized controlled trials). A summary of pooled MD between the %HVPG reduction is as follows: overall -8.62 (confidence interval [CI] -11.76, -5.48, P

The Daya Bay experiment was the first to report simultaneous measurements of reactor antineutrinos at multiple baselines leading to the discovery of ν¯e oscillations over km-baselines. Subsequent data has provided the world's most precise measurement of sin22θ13 and the effective mass splitting Δmee2. The experiment is located in Daya Bay, China where the cluster of six nuclear reactors is among the world's most prolific sources of electron antineutrinos. Multiple antineutrino detectors are deployed in three underground water pools at different distances from the reactor cores to search for deviations in the antineutrino rate and energy spectrum due to neutrino mixing. Instrumented with photomultiplier tubes, the water pools serve as shielding against natural radioactivity from the surrounding rock and provide efficient muon tagging. Arrays of resistive plate chambers over the top of each pool provide additional muon detection. The antineutrino detectors were specifically designed for measurements of the antineutrino flux with minimal systematic uncertainty. Relative detector efficiencies between the near and far detectors are known to better than 0.2%. With the unblinding of the final two detectors' baselines and target masses, a complete description and comparison of the eight antineutrino detectors can now be presented. This paper describes the Daya Bay detector systems, consisting of eight antineutrino detectors in three instrumented water pools in three underground halls, and their operation through the first year of eight detector data-taking.

This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse β decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18)  cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43)  cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.

We report a new measurement of electron antineutrino disappearance using the fully constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9×10^{5} GW_{th}  ton days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six ^{241}Am-^{13}C radioactive calibration sources reduced the background by a factor of 2 for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of sin^{2}2θ_{13} and |Δm_{ee}^{2}| were halved as a result of these improvements. An analysis of the relative antineutrino rates and energy spectra between detectors gave sin^{2}2θ_{13}=0.084±0.005 and |Δm_{ee}^{2}|=(2.42±0.11)×10^{-3}  eV^{2} in the three-neutrino framework.

The Daya Bay experiment consists of functionally identical antineutrino detectors immersed in pools of ultrapure water in three well-separated underground experimental halls near two nuclear reactor complexes. These pools serve both as shields against natural, low-energy radiation, and as water Cherenkov detectors that efficiently detect cosmic muons using arrays of photomultiplier tubes. Each pool is covered by a plane of resistive plate chambers as an additional means of detecting muons. Design, construction, operation, and performance of these muon detectors are described.

A new measurement of the $\theta_{13}$ mixing angle has been obtained at theDaya Bay Reactor Neutrino Experiment via the detection of inverse beta decaystagged by neutron capture on hydrogen. The antineutrino events for hydrogencapture are distinct from those for gadolinium capture with largely differentsystematic uncertainties, allowing a determination independent of thegadolinium-capture result and an improvement on the precision of $\theta_{13}$measurement. With a 217-day antineutrino data set obtained with sixantineutrino detectors and from six 2.9 GW$_{th}$ reactors, the rate deficitobserved at the far hall is interpreted as $\sin^22\theta_{13}=0.083\pm0.018$in the three-flavor oscillation model. When combined with thegadolinium-capture result from Daya Bay, we obtain$\sin^22\theta_{13}=0.089\pm0.008$ as the final result for thesix-antineutrino-detector configuration of the Daya Bay experiment.

A new measurement of the $\theta_{13}$ mixing angle has been obtained at theDaya Bay Reactor Neutrino Experiment via the detection of inverse beta decaystagged by neutron capture on hydrogen. The antineutrino events for hydrogencapture are distinct from those for gadolinium capture with largely differentsystematic uncertainties, allowing a determination independent of thegadolinium-capture result and an improvement on the precision of $\theta_{13}$measurement. With a 217-day antineutrino data set obtained with sixantineutrino detectors and from six 2.9 GW$_{th}$ reactors, the rate deficitobserved at the far hall is interpreted as $\sin^22\theta_{13}=0.083\pm0.018$in the three-flavor oscillation model. When combined with thegadolinium-capture result from Daya Bay, we obtain$\sin^22\theta_{13}=0.089\pm0.008$ as the final result for thesix-antineutrino-detector configuration of the Daya Bay experiment.

A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)

A measurement of the energy dependence of antineutrino disappearance at the Daya Bay reactor neutrino experiment is reported. Electron antineutrinos (ν¯(e)) from six 2.9  GW(th) reactors were detected with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls. Using 217 days of data, 41 589 (203 809 and 92 912) antineutrino candidates were detected in the far hall (near halls). An improved measurement of the oscillation amplitude sin(2)2θ(13)=0.090(-0.009)(+0.008) and the first direct measurement of the ν¯(e) mass-squared difference |Δm(ee)2|=(2.59(-0.20)(+0.19))×10(-3)  eV2 is obtained using the observed ν¯(e) rates and energy spectra in a three-neutrino framework. This value of |Δm(ee)2| is consistent with |Δm(μμ)2| measured by muon neutrino disappearance, supporting the three-flavor oscillation model.

Global interest in lithium-sulfur batteries as one of the most promising energy storage technologies has been sparked by their low sulfur cathode cost, high gravimetric, volumetric energy densities, abundant resources, and environmental friendliness. However, their practical application is significantly impeded by several serious issues that arise at the cathode-electrolyte interface, such as interface structure degradation including the uneven deposition of Li 2 S, unstable cathode-electrolyte interphase (CEI) layer and intermediate polysulfide shuttle effect. Thus, an optimized cathode-electrolyte interface along with optimized electrodes is required for overall improvement. Herein, we comprehensively outline the challenges and corresponding strategies, including electrolyte optimization to create a dense CEI layer, regulating the Li 2 S deposition pattern, and inhibiting the shuttle effect with regard to the solid-liquid-solid pathway, the transformation from solid-liquid-solid to solid-solid pathway, and solid-solid pathway at the cathode-electrolyte interface. In order to spur more perceptive research and hasten the widespread use of lithium-sulfur batteries, viewpoints on designing a stable interface with a deep comprehension are also put forth., Competing Interests: Declarations. Conflict of interest: The authors declare no interest conflict. They have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Although it is an effective treatment for acute myeloid leukemia (AML), chemotherapy leads to myelosuppression and poor hematopoietic reconstruction. Hematopoiesis is regulated by bone marrow (BM) endothelial cells (ECs), and BM ECs are dysfunctional in acute leukemia patients with poor hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation. Thus, it is crucial to explore the underlying mechanism of EC impairment and establish strategies for targeted therapy. TGF-β signaling was found to be upregulated in ECs from AML patients in complete remission (CR ECs) and led to CR EC damage. Administration of a TGF-β inhibitor rescued the dysfunction of ECs caused by TGF-β1 expression in vitro, especially their hematopoiesis-supporting ability. Moreover, inhibition of TGF-β expression repaired the BM EC damage triggered by chemotherapy in both AML patients in vitro and in an AML-CR murine model, and restored normal hematopoiesis without promoting AML progression. Mechanistically, our data reveal alterations in the transcriptomic pattern of damaged BM ECs, accompanied by the overexpression of downstream molecules TGF-βR1, pSmad2/3, and functional genes related to adhesion, angiogenesis suppression and pro-apoptosis. Collectively, our findings reveal for the first time that the activation of TGF-β signaling leads to BM EC dysfunction and poor hematopoietic reconstitution. Targeting TGF-β represents a potential therapeutic strategy to promote multilineage hematopoiesis, thereby benefiting more cancer patients who suffer from myelosuppression after chemotherapy., Competing Interests: Declaration of competing interest The authors wish to confirm that there are no known conflicts of interest associated with this publication. All co-authors have seen and approved this version of the manuscript and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Previous studies have detected microplastics (MPs) in human biological samples, such as lungs, alveolar lavage fluid, and thrombus. However, whether MPs induce health effects after inhalation are unclear. In this study, fluorescent polystyrene microplastics (PS-MPs) were found in the thymus, spleen, testes, liver, kidneys, and brain on day 1 or day 3 after one intratracheal instillation. Furthermore, mice showed inflammation in multiple organs, manifested as obvious infiltration of neutrophils and macrophages, increased Toll-like receptors (TLRs), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor-κB (NF-κB), as well as proinflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β) in the lungs, thymus, spleen, liver, and kidneys after four intratracheal instillations of PS-MPs at once every 2 weeks. Hepatic and renal function indexes were also increased. Subsequently, the inflammatory response in multiple murine organs was significantly alleviated by TLR2 and TLR4 inhibitors. Unexpectedly, we did not find any elevated secretion of monocyte chemotactic protein (MCP)-1 or TNF-α by RAW264.7 macrophages in vitro. Thus, PS-MPs induced inflammatory injuries in multiple murine organs via the TLRs/MyD88/NF-κB pathway in vivo, but not macrophages in vitro. These results may provide theoretical support for healthy protection against PS-MPs and their environmental risk assessment.

The four matrine-derived alkaloids, namely sophflarines B-E (1-4), with distinct skeleton types, were isolated from Sophora flavescens. Compounds 1 and 2 possess rare 1-aza-11-oxatricyclo[5.3.1.0 2,6 ] undecane cores, featuring unprecedented N,O-heterocyclic systems of 5/5/6/6/6 and 6/5/5/6/6, respectively. Compounds 3 and 4 exhibit two novel C 15 units with tetracyclic skeletons of 5/6/6/6 and 6/5/6/6, respectively. The structures were elucidated through spectroscopic analyses, quantum chemical calculations, and X-ray diffraction data. A plausible biosynthetic pathway for these newly discovered compounds was proposed. Furthermore, compounds 1 and 2 showed anti-neuroinflammatory activity against the cytokines NO, TNF-α, and IL-6. Compound 2 exhibited a neuroprotective effect potentially mediated by activating the Keap1-Nrf2/HO-1 pathway to reduce inflammation and oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Acquired vulvar lymphangioma (AVL), a rare disease caused by the dilation of superficial lymphatic vessels secondary to deep lymphatic vessel injury, is characterized by a wide range of morphological diversity and massive exudate. This morphological heterogeneity has often led to misdiagnosis or non-diagnosis. The management of AVL presents a therapeutic challenge due to the absence of a standardized treatment protocol., Case Presentation: A 53-year-old female patient, previously received surgical treatments for stage IIb cervical squamous cell carcinoma, presented with vulvar enlargement and copious amount of yellow exudate seven years post-treatment. Clinically, the patient exhibited chronic vulvar swelling, with easily-exudated nodules. The vulvar biopsy revealed lymphatic vessel dilation with lymphocyte infiltration, consistent with AVL. Due to the extensive lesions and severe exudate, staged excisions of bilateral vulvar lesions were performed at one-month intervals. Follow-up examinations of this patient for one-year post-surgery showed no evidence of recurrence., Conclusion: In this instance, AVL manifest secondary to cervical cancer surgery, as a result of damage to the deep lymphatic vessels of the vulva, with characteristic symptoms of copious amounts of exudate and vulvar lesions with diverse morphologies, which provides a cautionary note for physicians. Besides, the staged resection strategy in this case may offer insights into surgical treatment protocol for extensive AVL., 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 © 2024 Hu, Fang, Lin, Kang, Lin and Xiao.)

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Two novel phenylpropanoids (compounds 1 and 2) and 11 known compounds were isolated from Smilax china L. Their structures were determined by NMR (1D and 2D) and high-resolution electrospray ionization mass spectrometry. Further, the cytotoxic activity of all the isolated compounds against HeLa, 4T1, and U251 tumor cells was evaluated using the cell counting kit-8 assay, revealing that compound 13 showed significant cytotoxicity toward HeLa cells. Further investigations explored the impact of compound 13 on the mitochondrial membrane potential, concentration of reactive oxygen species, wound-healing distance, and cell cycle of HeLa cells. Notably, compound 13 significantly decreased mitochondrial membrane potential, suppressed cell migration, and increased intracellular reactive oxygen species levels in HeLa cells. Furthermore, compound 13 inhibited HeLa cell-cycle progression in the S phase. These findings indicate that compound 13 is a potential drug lead for the treatment of cervical cancer., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Introduction: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo-geneic hematopoiesis stem cell transplantation (allo-HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome., Methods: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation. Abnormal CSF (CSF+) was detected via conventional cytology and MFC in 44 patients at any time after diagnosis. A control group of 175 CSF-normal (CSF-) patients was generated via propensity score matching (PSM) analyses according to sex, age at transplant, and white blood cell count at diagnosis., Results: Compared to those in the CSF-negative group, the conventional cytology positive and MFC+ groups had comparable 8-year nonrelapse mortality (NRM) (4%, 4%, and 6%, p = 0.82), higher cumulative incidence of relapse (CIR) (14%, 31%, and 32%, p = 0.007), lower leukemia-free survival (LFS) (79%, 63%, and 64%, p = 0.024), and overall survival (OS) (83%, 63%, and 68%, p = 0.021), with no significant differences between the conventional cytology positive and MFC+ groups. Furthermore, multivariate analysis confirmed that CSF involvement was an independent factor affecting OS and LFS., Conclusion: Our results indicate that pretransplant CSF abnormalities are adverse factors independently affecting OS and LFS after allotransplantation in AML patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis., Design: Prospective multicentre diagnostic accuracy study., Setting: 14 medical centres in China., Participants: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1., Main Outcome Measures: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices., Results: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE., Conclusion: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis., Trial Registration: ClinicalTrials.gov NCT03748563., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the “Ten Thousand Plan”-National High-Level Talents Special Support Plan and Shanghai Municipal Hospital Emerging Frontier Technology Joint Project for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Four undescribed coumarin derivatives, ficusalt A (1) and ficusalt B (2), a pair of racemic coumarins, (±) ficudimer A (3a/3b), along with ten known amides, were isolated from the roots of Ficus hirta. Their structures were elucidated by several spectroscopic data analyses, including HRESIMS, NMR, and X-ray single-crystal diffraction. The cytotoxic activities of all compounds against HeLa, HepG2, MCF-7, and H460 cell lines were detected using the MTT assay. Among these, 5 showed the highest activity against HeLa cells. Subsequently, the apoptotic, anti-invasive, and anti-migration effects of 5 on HeLa cells were determined by flow cytometer, transwell invasion assay, and wound-healing assay, respectively. The result suggested that 5 distinctly induced the apoptosis in HeLa cells and inhibited their invasion and migration. Further studies on anticancer mechanisms were conducted using Western blotting. As a result, 5 increased the cleavage of PARP and the expression of pro-apoptotic protein Bax. Moreover, 5 notably upregulated the phosphorylation of p38 and JNK, whereas inhibited the expression of p-ERK and p-AKT. Our results demonstrated that 5 could be a potential leading compound for further application in the treatment of cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment., Methods: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I 2 ), to analyze the clinical outcome of FSG., Results: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups., Conclusions: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aims to investigate the effect of Naotaifang(NTF) on the proteins associated with microglial polarization and glial scar in the rat model of cerebral ischemia reperfusion injury(CIRI). The CIRI model was established by middle cerebral artery occlusion/reperfusion. The 48 successfully modeled rats were randomized into model 7 d, model 14 d, NTF 7 d, and NTF 14 d groups(n=12). In addition, 12 SD rats were selected as the sham group. The NTF group was administrated with NTF suspension at 27 g·kg~(-1)·d~(-1) by gavage, and the sham, model 7 d, and model 14 d groups were administrated with the same volume of normal saline every day by gavage for 7 and 14 days, respectively. After the intervention, Longa score was evaluated. The infarct volume was measured by 2,3,5-triphenyl-2H-tetrazolium chloride(TTC) staining. Morris water maze and open field tests were carried out to evaluate the spatial learning, memory, cognitive function, and anxiety degree of rats. Hematoxylin-eosin(HE) staining was employed to observe the morphological structure and damage of the brain tissue. The immunofluorescence assay was employed to measure the expression of glial fibrillary acidic protein(GFAP) and glial scar. Western blot was employed to determine the protein levels of GFAP, neurocan, phosphacan, CD206, arginase-1(Arg-1), interleukin(IL)-1β, IL-6, and IL-4. Compared with the sham, model 7 d and model 14 d groups showed cerebral infarction of different degrees, severe pathological injury of cerebral cortex and hippocampus, neurological impairment, reduced spatial learning and memory, cognitive dysfunction, severe anxiety, astrocyte hyperplasia, thickening penumbra glial scar, and up-regulated protein levels of IL-1β, IL-6, GFAP, neurocan, phosphacan, CD206, and Arg-1(P&lt;0.01). Compared with the model group, NTF 7 d and NTF 14 d groups improved spatial learning, memory, and cognitive function, reduced anxiety, improved nerve function, reduced cerebral infarction volume, reduced astrocyte hyperplasia, thinned penumbra glial scar, down-regulated the protein levels of GFAP, neurocan, phosphacan, IL-6, and IL-1β, and up-regulated the protein levels of IL-4, CD206, and Arg-1(P&lt;0.05 or P&lt;0.01). NTF exerts a neuroprotective effect on CIRI by inducing the M2 polarization of microglia, inhibiting inflammatory response, and reducing the formation of glial scar.

A synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A-F, a cinnamoylphloroglucinol collection discovered from Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5-benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6-addition/enol-keto tautomerism cascade reaction for the construction of the dihydropyrano[3,2-d]xanthene tetracyclic core of cleistoperlones A and B, and a rare inverse-electron-demand hetero-Diels-Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D-F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1/Blue and HSV-1/153)., (© 2023 Wiley-VCH GmbH.)

Familial hypercholesterolemia (FH) is a common hereditary cholesterol metabolic disease that usually leads to an increase in the level of low-density lipoprotein cholesterol in plasma and an increase in the risk of cardiovascular disease. The lack of disease screening and diagnosis often results in FH patients being unable to receive early intervention and treatment, which may mean early occurrence of cardiovascular disease. Thus, more requirements for FH identification and management have been proposed. Recently, machine learning (ML) has made great progress in the field of medicine, including many innovative applications in cardiovascular medicine. In this review, we discussed how ML can be used for FH screening, diagnosis and risk assessment based on different data sources, such as electronic health records, plasma lipid profiles and corneal radian images. In the future, research aimed at developing ML models with better performance and accuracy will continue to overcome the limitations of ML, provide better prediction, diagnosis and management tools for FH, and ultimately achieve the goal of early diagnosis and treatment of FH., 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., (© 2023 Luo, Wang, Hu, Fu, Zhang and Jiang.)

Natural restoration has often been considered an effective measure for rehabilitating degraded ecosystems. However, its impact on the structure and diversity of soil microbial communities, particularly within a salinized grassland during its restoration succession, remains unclear. In this study, we examined the effects of natural restoration on the Shannon-Wiener diversity index, Operational Taxonomic Units (OTU) richness, and structure of the soil microbial community of a sodic-saline grassland in China using high-throughput amplicon sequencing data from representative successional chronosequences. Our results indicated that natural restoration resulted in a significant mitigation of the grassland salinization (pH from 9.31 to 8.32 and electrical conductivity from 393.33 to 136.67 μs·cm -1 ) and a significant alteration of the soil microbial community structure of the grassland (p < 0.01). However, the effects of natural recovery differed in terms of the abundance and diversity of bacteria and fungi. For example, the relative abundance of the bacterial phyla Acidobacteria increased by 116.45 % in the topsoil and 339.03 % in the subsoil, while that of the fungal phyla Ascomycota decreased by 8.86 % in the topsoil and 30.18 % in the subsoil. There was no significant effect of restoration on bacterial diversity, but fungal diversity increased by 15.02 % in the Shannon-Wiener index and 62.20 % in the OTU richness in the topsoil. Model-selection analysis further corroborated that the alteration of the soil microbial structure by natural restoration may be due to the fact that the bacteria could adapt to the alleviated salinized grassland soil and the fungi could adapt to the improved soil fertility of the grasslands. Overall, our results contribute to an in-depth understanding of the impacts of natural restoration on soil microbial diversity and community structure in salinized grasslands during the long-term successional course. This may also help to apply natural restoration as a greener practice option for managing degraded ecosystems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Liang-Jun Hu reports financial support was provided by Chinese Academy of Sciences. Liang-Jun Hu reports financial support was provided by National Natural Science Foundation of China. Liang-Jun Hu reports financial support was provided by Ministry of Science & Technology of China. Weina Wang reports financial support was provided by China Scholarship Council. Huanjun Liu reports financial support was provided by Chinese Academy of Sciences. Lifei Chen reports financial support was provided by National Natural Science Foundation of China. Kadri Koorem declares no interest of this paper. Yingchao Hu declares no interest of this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lipase is involved in lipid hydrolysis, which is related to nematodes' energy reserves and stress resistance. However, the role of lipases in Bursaphelenchus xylophilus, a notorious plant-parasitic nematode responsible for severe damage to pine forest ecosystems, remains largely obscure. Here, we characterized a class III lipase as a candidate effector and named it BxLip-3. It was transcriptionally up-regulated in the parasitic stages of B. xylophilus and specifically expressed in the oesophageal gland cells and the intestine. In addition, BxLip-3 suppressed cell death triggered by the pathogen-associated molecular patterns PsXEG1 and BxCDP1 in Nicotiana benthamiana, and its Lipase-3 domain is essential for immunosuppression. Silencing of the BxLip-3 gene resulted in a delay in disease onset and increased the activity of antioxidant enzymes and the expression of pathogenesis-related (PR) genes. Plant chitinases are thought to be PR proteins involved in the defence system against pathogen attack. Using yeast two-hybrid and co-immunoprecipitation assays, we identified two class I chitinases in Pinus thunbergii, PtChia1-3 and PtChia1-4, as targets of BxLip-3. The expression of these two chitinases was up-regulated during B. xylophilus inoculation and inhibited by BxLip-3. Overall, this study illustrated that BxLip-3 is a crucial virulence factor that plays a critical role in the interaction between B. xylophilus and host pine., (© 2023 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Background: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation that arises in the context of infectious, inflammatory, or neoplastic triggers. The aim of this study was to establish a predictive model for the timely differential diagnosis of the original disease resulting in HLH by validating clinical and laboratory findings to further improve the efficacy of therapeutics for HLH., Methods: We retrospectively enrolled 175 secondary HLH patients in this study, including 92 patients with hematologic disease and 83 patients with rheumatic disease. The medical records of all identified patients were retrospectively reviewed and used to generate the predictive model. We also developed an early risk score using multivariate analysis weighted points proportional to the β regression coefficient values and calculated its sensitivity and specificity for the diagnosis of the original disease resulting in HLH., Results: The multivariate logistic analysis revealed that lower levels of hemoglobin and platelets (PLT), lower levels of ferritin, splenomegaly and Epstein-Barr virus (EBV) positivity were associated with hematologic disease, but young age and female sex were associated with rheumatic disease. The risk factors for HLH secondary to rheumatic diseases were female sex [OR 4.434 (95% CI, 1.889-10.407), P =0.001], younger age [OR 6.773 (95% CI, 2.706-16.952), P <0.001], higher PLT level [OR 6.674 (95% CI, 2.838-15.694), P <0.001], higher ferritin level [OR 5.269 (95% CI, 1.995-13.920), P =0.001], and EBV negativity [OR 27.656 (95% CI, 4.499-169.996), P <0.001]. The risk score included assessments of female sex, age, PLT count, ferritin level and EBV negativity, which can be used to predict HLH secondary to rheumatic diseases with an AUC of 0.844 (95% CI, 0.836~0.932)., Conclusion: The established predictive model was designed to help clinicians diagnose the original disease resulting in secondary HLH during routine practice, which might be improve prognosis by enabling the timely treatment of the underlying disease., 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 Gao, Hu, Ma, Shi, Wang, Ma, Song, Zhu and Wang.)

Microbial graphene oxide reduction is a developing method that serves to reduce both production costs and environmental impact in the synthesis of graphene. This study demonstrates microbial graphene oxide reduction using Shewanella decolorationis NTOU1 under neutral and mild conditions (pH = 7, 35 °C, and 1 atm). Graphene oxide (GO) prepared via the modified Hummers' method is used as the sole solid electron acceptor, and the characteristics of reduced GO (rGO) are investigated. According to electron microscopic images, the surface structure of GO was clearly changed from smooth to wrinkled after reduction, and whole cells were observed to be wrapped by GO/rGO films. Distinctive appendages on the cells, similar to nanowires or flagella, were also observed. With regard to chemical-bonding changes, after a 24-h reaction of 1 mg mL -1 , GO was reduced to rGO, the C/O increased from 1.4 to 3.0, and the oxygen-containing functional groups of rGO were significantly reduced. During the GO reduction process, the number of S. decolorationis NTOU1 cells decreased from 1.65 × 10 8 to 1.03 × 10 6 CFU mL -1 , indicating the bactericide effects of GO/rGO. In experiments adding consistent concentrations of initial bacteria and lactate, it was shown that with the increase of GO additions (0.5-5.0 mg mL -1 ), the first-order reaction rate constants ( k ) of lactate metabolism and acetate production increased accordingly; in experiments adding consistent concentrations of initial bacteria and GO but different lactate levels (1 to 10 mM), the k values of lactate metabolism did not change significantly. The test results of adding different electron transfer mediators showed that riboflavin and potassium ferricyanide were able to boost GO reduction, whereas 2,6-dimethoxy-1,4-benzoquinone and 2,6-dimethyl benzoquinone completely eliminated bacterial activity.

Background: Swelling after apical microsurgery is a postoperative reaction and may reduce quality of life during healing., Aim: To evaluate periapical swelling after apical microsurgery and determine potential risk factors., Methods: Ninety-eight apical microsurgery patients were selected for this study. Before surgery, bone shadow volume and density of pathological tissue were measured by cone beam computed tomography. The other variables (age, gender, operative teeth number, fistula, preoperative swelling, drug use and preoperative root canal treatments) were assessed during examination. Swelling degree was confirmed by questionnaires for patients on postoperative days 1, 7, 14 and 21. Statistical analyses were performed to identify predictors for swelling., Results: Majority of patients reported moderate (45.9%) or severe (34.7%) swelling on day 1, and moderate (44.9%) or mild (45.9%) on postoperative day 7. Ninety-nine percent of patients had no or mild swelling on postoperative day 14. The average swelling level peaked on day 1 postoperatively and gradually decreased. Of statistical significance, age, bone shadow volume and density of pathological tissue acted as predictors of swelling ( P < 0.05). However, there was no significant difference in gender, tooth number, fistula, preoperative swelling, drug use, or preoperative root canal treatments ( P > 0.05)., Conclusion: Younger patients with larger shadow volume and density were significantly more likely to develop swelling after apical microsurgery., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Enoyl-CoA hydratase domain containing 3 (ECHDC3) increased in CD34 + progenitor cells of acute myeloid leukemia (AML) cells after chemotherapy. However, the prognostic significance and function of ECHDC3 in AML remain to be clarified., Methods: In the training cohort, 24 AML (non-acute promyelocytic leukemia, APL) patients were enrolled in Peking University People's Hospital and tested for ECHDC3 in enriched CD34 + cells at diagnosis. In the validation set, 351 bone marrow RNA-seq data of non-APL AML were obtained by two independent online datasets (TCGA-LAML and BEAT-AML). LASSO regression model was conducted to a new prediction model of ECHDC3-related genes. In addition, the ECHDC3 signature was further explored by GO, KEGG, GSEA, and immuno-infiltration analysis. By RNA interference, the function of ECHDC3 in mitochondrial DNA (mt-DNA) transcriptome and chemoresistance was further explored, and the GSE52919 database re-verified the ECHDC3 chemoresistance feature., Results: By Kaplan-Meier analysis, patients with ECHDC3 high demonstrated inferior overall survival (OS) compared to those with ECHDC3 low both in the training (2-year OS, 55.6% vs . 100%, p = 0.011) and validation cohorts (5-year OS, 9.6% vs . 24.3%, p = 0.002). In addition, ECHDC3 high predicted inferior OS in the subgroup of patients with ELN 2017 intermediated (int) risk (5-year OS, 9.5% vs . 26.3%, p = 0.039) or FLT3+NPM1- adverse (adv) risk (4-year OS, 6.4% vs . 31.8%, p = 0.003). In multivariate analysis, ECHDC3 was an independent risk factor of inferior OS (HR 1.159, 95% CI 1.013-1.326, p = 0.032). In the prediction model combining ECHDC3 and nine selected genes (RPS6KL1, RELL2, FAM64A, SPATS2L, MEIS3P1, CDCP1, CD276, IL1R2, and OLFML2A) by Lasso regression, patients with high risk showed inferior 5-year OS (9.3% vs . 23.5%, p < 0.001). Bioinformatic analysis suggested that ECHDC3 alters the bone marrow microenvironment by inducing NK, resting mast cell, and monocyte differentiation. Knocking down ECHDC3 in AML cells by RNAi promoted the death of leukemia cells with cytarabine and doxorubicin., Conclusion: These bioinformatic analyses and experimental verification indicated that high ECHDC3 expression might be a poor prognostic biomarker for non-APL AML, which might be a potential target for reverting chemoresistance., 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 Zhao, Niu, Hu and Lv.)

Objective: This study aimed to explore variables associated with remission rate and survival in patients with acute myeloid leukemia (AML) after induction failure and relapse. Methods: Data of 373 consecutive patients with AML were analyzed after induction failure and relapse. Binary logistics and the Cox model regression were used to identify variables associated with remission rate and outcomes. Results: In patients with AML after induction failure and relapse, the total CR+CRi rates were 50.6% and 40.3%, respectively; among those who achieved CR/CRi, the 3-year RFS rates were 34.4% and 30.4%, respectively, and the 3-year overall survival rates were 40.1% and 31.6%, respectively. In the multivariate analyses, using CLAG or FLAG regimen as a re-induction chemotherapy regimen, age <39 years and SWOG low-risk were significantly associated with higher remission rates in patients with induction failure. Male, secondary AML, SWOG high-risk, the interval from the first remission to relapse within 12 months, and bone marrow blasts ≥20% at the time of relapse were significantly associated with lower remission rates in relapsed patients. Transplantation was significantly associated with prolonged relapse-free survival and overall survival in patients achieving hematologic remission; the SWOG low-risk group was significantly associated with longer overall survival in those with induction failure; and achieving CR (not CRi) or having female gender was associated with longer RFS or overall survival in relapsed patients. Conclusion: Reinduction chemotherapy regimen, age, gender, SWOG risk, secondary AML, the interval from the first remission to relapse, and bone marrow blast percentage at the time of relapse were significantly associated with remission rates in the patients with AML after induction failure and relapse. Transplantation, SWOG low-risk, achieving CR, or female gender were associated with longer survivals in those achieving remission.

The migratory plant-parasitic nematode Bursaphelenchus xylophilus is the pathogen of the pine wilt disease (PWD), causing serious damage to pine forests in China. During the process of plant resistance to multiple pathogens, plant immunity plays a key role. In this current study, the pathogen-associated molecular pattern (PAMP) BxCDP1 in B. xylophilus has been identified, but the host target protein of BxCDP1 and its key amino acid region inducing the plant immunity have yet to be elucidated. We found that BxCDP1 could trigger superoxide production, H 2 O 2 production, and callose deposits. A RING-H2 finger protein 1 (RHF1) of Pinus thunbergii was screened and characterized as a target protein of BxCDP1 by yeast two-hybrid and co-immunoprecipitation (Co-IP). Moreover, two peptides (namely M9 and M16) proved to be key regions of BxCDP1 to induce PAMP-triggered immunity (PTI) in Nicotiana benthamiana , which also induced the expression of pathogenesis-related (PR) genes ( PtPR-3 , PtPR-4 , and PtPR-5 ) in P. thunbergii and enhanced the resistance of the host to B. xylophilus . These results indicate that BxCDP1 plays a critical role in the interaction between B. xylophilus and P. thunbergii , and both peptides M9 and M16 have the potential to be developed and utilized as immune inducers of pines against B. xylophilus in future., 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 Hu, Wu, Wen, Ye, Qiu, Rui and Zhang.)

Objective: The study aims to explore the efficacy and safety of low-dose chemotherapy combined with tyrosine kinase inhibitor (TKI) as an induction therapy for Philadelphia-chromosomal-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: The data of the consecutive newly diagnosed patients with Ph(+) ALL were reviewed. The efficacy and safety of low-dose chemotherapy and conventional-dose chemotherapy combined with TKI were compared. Results: A total of 217 patients with a median age of 38 (10-69) years old were included in this study. 78 patients were in the low-dose chemotherapy group, and 139 patients were in the conventional-dose chemotherapy group. There were no significant differences in the 4-week complete remission (CR) rate (98.7% vs 97.0%, P =0.766) and overall CR rate (100% vs 100%, P =1.000) between the two groups. Multivariate analyses showed that the chemotherapy intensity was not related to the disease-free survival rate and overall survival rate. However, the lower incidence of infection ( P =0.017) , the shorter duration of neutropenia ( P =0.001) and PLT<20 × 10(9)/L ( P =0.057) , and the lower red blood cell transfusion volume ( P =0.002) were more common in the low-dose chemotherapy group than in the conventional-dose chemotherapy group. Conclusions: The low-dose chemotherapy is superior to the conventional-dose chemotherapy combined with TKI as induction therapy in Ph(+) ALL with similar efficacy but is safer.

Bursaphelenchus xylophilus is the most economically important species of migratory plant-parasitic nematodes (PPNs) and causes severe damage to forestry in China. The successful infection of B. xylophilus relies on the secretion of a repertoire of effector proteins. The effectors, which suppress the host pine immune response, are key to the facilitation of B. xylophilus parasitism. An exhaustive list of candidate effectors of B. xylophilus was predicted, but not all have been identified and characterized. Here, an effector, named BxSCD3, has been implicated in the suppression of host immunity. BxSCD3 could suppress pathogen-associated molecular patterns (PAMPs) PsXEG1- and INF1-triggered cell death when it was secreted into the intracellular space in Nicotiana benthamiana. BxSCD3 was highly up-regulated in the early infection stages of B. xylophilus . BxSCD3 does not affect B. xylophilus reproduction, either at the mycophagous stage or the phytophagous stage, but it contributes to the virulence of B. xylophilus. Moreover, BxSCD3 significantly influenced the relative expression levels of defense-related (PR) genes PtPR-3 and PtPR-6 in P inus thunbergii in the early infection stage. These results suggest that BxSCD3 is an important toxic factor and plays a key role in the interaction between B. xylophilus and host pine.

Background: Bursaphelenchus xylophilus is the causal agent of pine wilt disease (PWD) that has caused enormous ecological and economic losses in China. The mechanism in the interaction between nematodes and pine remains unclear. Plant parasitic nematodes (PPNs) secrete effectors into host plant tissues. However, it is poorly studied that role of effector in the infection of pine wood nematode (PWN)., Results: We cloned, characterized and functionally validated the B. xylophilus effector BxML1, containing an MD-2-related lipid-recognition (ML) domain. This protein inhibits immune responses triggered by the molecular pattern BxCDP1 of B. xylophilus. An insitu hybridization assay demonstrated that BxML1 was expressed mainly in the dorsal glands and intestine of B. xylophilus. Subcellular localization analysis showed the presence of BxML1 in the cytoplasm and nucleus. Furthermore, number of B. xylophilus and morbidity of pine were significantly reduced in Pinus thunbergii infected with B. xylophilus when BxML was silenced. Using yeast two-hybrid (Y2H) and coimmunoprecipitation (CoIP) assays, we found that the BxML1 interacts with cyclophilin protein PtCyP1 in P. thunbergii., Conclusions: This study illustrated that BxML1 plays a critical role in the B. xylophilus-plant interaction and virulence of B. xylophilus., (© 2022. The Author(s).)

Inspired by a previously reported biomimetic synthesis study, four new naturally occurring phloroglucinol trimers 1-4 with unusual 6/5/5/6/6/6-fused hexacyclic ring systems, along with two known analogues ( 5 and 6 ) and two known biogenetically related dimers ( 10 and 11 ), were isolated from Rhodomyrtus tomentosa . Their structures and absolute configurations were unambiguously elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism calculation. By mimicking two potentially alternative biosynthetic pathways, the first asymmetric syntheses of 1-4 and the racemic syntheses of 5 and 6 were achieved in only five to six steps without the need for protecting groups. Furthermore, phloroglucinol dimers 10 and 11 exhibited significant in vitro antiviral activity against the respiratory syncytial virus.

A new chromone glycoside, 8- O - β -D-Glucopyranosyl-2-methylchromone ( 1 ), together with eight known compounds ( 2 - 9 ) were isolated from the Tibetan medicine plant of Swertia punicea . All compounds of this plant were reported for the first time. The structures of these metabolites were elucidated by analysis of their HR-ESI-MS, 1D and 2D NMR spectroscopic data and comparison with data reported in the literature. In vitro test, all compounds were evaluated for their anti-inflammatory activity through the determination of nitric oxide production. Compounds 1 - 2 were evaluated for cytotoxic activities against three human cancer cell lines (HeLa, MDA-MB-231 and A375) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Furthermore, the chemotaxonomic significance of these compounds has also been described.

The plant-parasitic nematode Bursaphelenchus xylophilus, the causal agent of pine wilt disease (PWD), causes enormous economic loss every year. Currently, little is known about the pathogenic mechanisms of PWD. Several effectors have been identified in B. xylophilus, but their functions and host targets have yet to be elucidated. Here, we demonstrated that BxSCD1 suppresses cell death and inhibits B. xylophilus PAMP BxCDP1-triggered immunity in Nicotiana benthamiana and Pinus thunbergii. BxSCD1 was transcriptionally upregulated in the early stage of B. xylophilus infection. In situ hybridization experiments showed that BxSCD1 was specifically expressed in the dorsal glands and intestine. Cysteine residues are essential for the function of BxSCD1. Transient expression of BxSCD1 in N. benthamiana revealed that it was primarily targeted to the cytoplasm and nucleus. The morbidity was significantly reduced in P. thunbergii infected with B. xylophilus when BxSCD1 was silenced. We identified 1-aminocyclopropane-1-carboxylate oxidase 1, the actual ethylene-forming enzyme, as a host target of BxSCD1 by yeast two-hybrid and coimmunoprecipitation. Overall, this study illustrated that BxSCD1 played a critical role in the B. xylophilus-plant interaction., (© 2021 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Objective: Rheumatoid arthritis (RA) patients are prone to develop thromboembolic complications due to the chronic inflammatory nature of RA. Only one systematic review and meta-analysis has attempted to evaluate venous thromboembolism risk in RA patients. However, this review has become outdated due to the recent publication of several high-quality retrospective cohort studies. The aim of the study was to evaluate the risks of deep vein thrombosis, pulmonary embolism, and overall venous thromboembolism event incidence in RA patients., Materials and Methods: Five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE) were systematically searched according to PRISMA guidelines for eligible studies. With the available literature, we conducted a random-effect meta-analysis to evaluate odds ratios of deep vein thrombosis, pulmonary embolism, and venous thromboembolism incidence in RA patients and healthy controls., Results: We found 12 eligible studies detailing 272,884 RA patients and 2,280,454 age and sex-matched healthy controls. Meta-analysis revealed elevated risks for deep vein thrombosis (Odd's ratio: 2.25), pulmonary embolism (2.15), and overall venous thromboembolism incidence (2.23) in RA patients., Conclusions: This meta-analysis provides evidence concerning the elevated risks of deep vein thrombosis, pulmonary embolism, and venous thromboembolism in RA patients. The findings herein may aid in developing clinical awareness and assisting best practice guideline development for RA patients with thromboembolic complications.

Background: Isocenter deviation, often induced by small displacements of both the device and the patient, is a common error seen in radiotherapy. In this study, we investigated the impact of isocenter deviation on the results of the volumetric modulated arc therapy (VMAT) plan and dosimetric verification gamma passing rate in the treatment of cervical cancer., Methods: The clinical data of 15 patients with cervical cancer who were treated with VMAT were retrospectively collected and analyzed. In this study, the isocenter site modification method was adopted. The VMAT plan with isocenter deviation adjustment was set as the experimental group, while the original plan was set as the control group. The impact of isocenter deviation on the results of the VMAT plan and dosimetric verification gamma passing rate was analyzed. Applying gamma analysis with different test criterions, the impact of isocenter deviation on the gamma passing rates was evaluated, and the sensitivity of different test criterions in identifying isocenter deviation was also analyzed., Results: There was a significant difference in the average dose in the target area between experimental group and control group (P<0.05). In organs at risk (OAR) terms, isocenter deviations also caused significant differences in dose parameters between the two groups. Except that there was no significant difference in the rectal V40 between two groups when the isocenter deviation was greater than 3 mm in the y axis direction. With the increase in the isocenter deviation, there was a trend towards decreased gamma passing rates with different analysis criterions in the experimental group. The 2 mm/2% standard had the highest sensitivity for identifying isocenter deviation., Conclusions: Isocenter deviation has significant effects on the results of the volume rotation intensity modulation plan and dosimetric verification gamma passing rates in the treatment of cervical cancer. When the isocenter deviation was less than 3 mm, a higher gamma passing rate (>90%) could also be obtained under the condition of the 3 mm/3% test criterions. It is recommended that the 2 mm/2% test standard should be utilized in clinical practice., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tcr-21-1514). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

A combined strategy of building blocks recognition and molecular network construction, termed the building blocks-based molecular network (BBMN), was first presented to facilitate the efficient discovery of novel natural products. By mapping the BBMN of the total alkaloid fraction of Flueggea suffruticosa, three Securinega alkaloids (SEAs) with unusual chemical architectures, suffranidines A-C (1-3), were discovered and isolated. Compound 1 characterizes an unprecedented 8/5/6/5/6/6/6/6-fused octacyclic scaffold with a unique cage-shaped 3-azatricyclo[6.4.0.0 3,11 ]dodecane core. Compounds 2 and 3 are highly modified SEA dimers that incorporate additional C6 motifs. A hypothetical biosynthetic pathway for 1-3 was proposed. In addition, 1 significantly induced neuronal differentiation and neurite extension by upregulating eukaryotic elongation factor 2 (eEF2)-mediated protein synthesis., (© 2021 Wiley-VCH GmbH.)

Rhodomentosones A and B ( 1 and 2 ), two pairs of novel enantiomeric phloroglucinol trimers featuring a unique 6/5/5/6/5/5/6-fused ring system were isolated from Rhodomyrtus tomentosa . Their structures with absolute configurations were elucidated by NMR spectroscopy, X-ray crystallography, and ECD calculation. The bioinspired syntheses of 1 and 2 were achieved in six steps featuring an organocatalytic asymmetric dehydroxylation/Michael addition/Kornblum-DeLaMare rearrangement/ketalization cascade reaction. Compounds 1 and 2 exhibited promising antiviral activities against respiratory syncytial virus (RSV).

Background: The pine wood nematode (PWN), Bursaphelenchus xylophilus, is a devastating pathogen of many Pinus species in China. The aim of this study was to understand the interactive molecular mechanism of PWN and its host by comparing differentially expressed genes and candidate effectors from three transcriptomes of B. xylophilus at different infection stages., Results: In total, 62, 69 and 46 candidate effectors were identified in three transcriptomes (2.5 h postinfection, 6, 12 and 24 h postinoculation and 6 and 15 d postinfection, respectively). In addition to uncharacterized pioneers, other candidate effectors were involved in the degradation of host tissues, suppression of host defenses, targeting plant signaling pathways, feeding and detoxification, which helped B. xylophilus survive successfully in the host. Seven candidate effectors were identified in both our study and the B. xylophilus transcriptome at 2.5 h postinfection, and one candidate effector was identified in all three transcriptomes. These common candidate effectors were upregulated at infection stages, and one of them suppressed pathogen-associated molecular pattern (PAMP) PsXEG1-triggered cell death in Nicotiana benthamiana., Conclusions: The results indicated that B. xylophilus secreted various candidate effectors, and some of them continued to function throughout all infection stages. These various candidate effectors were important to B. xylophilus infection and survival, and they functioned in different ways (such as breaking down host cell walls, suppressing host defenses, promoting feeding efficiency, promoting detoxification and playing virulence functions). The present results provide valuable resources for in-depth research on the pathogenesis of B. xylophilus from the perspective of effectors.

Study Objective: It is controversial whether local anesthetic dose requirement for spinal anesthesia for cesarean delivery differs between patients with singleton and patients with multiple gestation pregnancies. The aim of this study was to determine and compare the ED 50 and ED 90 for hyperbaric ropivacaine used for spinal anesthesia for cesarean delivery in patients with singleton pregnancies versus patients with twin pregnancies., Design: Prospective, randomized, comparative dose-finding study., Setting: Operating room, Women's Hospital, Zhejiang University School of Medicine., Patients: 100 patients with singleton pregnancies (Group S) and 100 patients with twin pregnancies (Group T) presenting for scheduled cesarean delivery under combined spinal-epidural anesthesia were enrolled in the study., Interventions: Patients in Group S or Group T were randomly allocated to receive 9.5, 11, 12.5, 14 or 15.5 mg of hyperbaric ropivacaine intrathecally. A dose was considered effective when it achieved a bilateral sensory block level at the T6 dermatome or above within 10 min after intrathecal injection, there was no numerical rating scale (NRS) pain score ≥ 3 intraoperatively, and there was no requirement for epidural supplementation at any time during anesthesia and operation. Values for ED 50 and ED 90 for ropivacaine were determined using probit regression. The difference in ropivacaine dose requirement between patients with singleton pregnancies and patients with twin pregnancies was assessed by calculating relative median potency., Measurements: Success rates for different intrathecal doses of ropivacaine, side effects and neonatal outcomes were recorded., Main Results: The estimated (95% confidence interval) values for ED 50 and ED 90 of intrathecal ropivacaine in patients with singleton pregnancies were 11.2 (10.2 to 12.0) mg and 15.7 (14.4 to 18.3) mg, respectively. The values for ED 50 and ED 90 in patients with twin pregnancies were 10.5 (9.5 to 11.3) mg and 14.8 mg (13.6 to 17.0) mg, respectively. The estimate of relative median potency for ropivacaine between patients with singleton and twin pregnancies was 0.94 (95% confidence interval 0.83 to 1.04)., Conclusion: Patients with singleton and twin pregnancies have similar dose requirement for hyperbaric ropivacaine used for spinal anesthesia for cesarean delivery in the setting of combined spinal-epidural (CSE) anesthesia, no opioids, low weight cohort, insertion with the patients in the right lateral position, and norepinephrine boluses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bufadienolides are cardioactive C24 steroids with an α-pyrone ring at position C17. In the last ten years, accumulating studies have revealed the anticancer activities of bufadienolides and their underlying mechanisms, such as induction of autophagy and apoptosis, cell cycle disruption, inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and stemness, and multidrug resistance reversal. As Na + /K + -ATPase inhibitors, bufadienolides have inevitable cardiotoxicity. Short half-lives, poor stability, low plasma concentration and oral bioavailability in vivo are obstacles for their applications as drugs. To improve the drug potency of bufadienolides and reduce their side effects, prodrug strategies and drug delivery systems such as liposomes and nanoparticles have been applied. Therefore, systematic and recapitulated information about the antitumor activity of bufadienolides, with special emphasis on the molecular or cellular mechanisms, prodrug strategies and drug delivery systems, is of high interest. Here, we systematically review the anticancer effects of bufadienolides and the molecular or cellular mechanisms of action. Research advancements regarding bufadienolide prodrugs and their tumor-targeting delivery strategies are critically summarized. This work highlights recent scientific advances regarding bufadienolides as effective anticancer agents from 2011 to 2019, which will help researchers to understand the molecular pathways involving bufadienolides, resulting in a selective and safe new lead compound or therapeutic strategy with improved therapeutic applications of bufadienolides for cancer therapy., (Copyright © 2020. Published by Elsevier B.V.)