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We study the direct production of the J^{PC}=1^{++} charmonium state χ_{c1}(1P) in electron-positron annihilation by carrying out an energy scan around the mass of the χ_{c1}(1P). The data were collected with the BESIII detector at the BEPCII collider. An interference pattern between the signal process e^{+}e^{-}→χ_{c1}(1P)→γJ/ψ→γμ^{+}μ^{-} and the background processes e^{+}e^{-}→γ_{ISR}J/ψ→γ_{ISR}μ^{+}μ^{-} and e^{+}e^{-}→γ_{ISR}μ^{+}μ^{-} is observed by combining all the data samples. The χ_{c1}(1P) signal is observed with a significance of 5.1σ. This is the first observation of a C-even state directly produced in e^{+}e^{-} annihilation. The electronic width of the χ_{c1}(1P) resonance is determined to be Γ_{ee}=(0.12_{-0.08}^{+0.13})  eV, which is of the same order of magnitude as theoretical calculations.

We study the processes e^{+}e^{-}→K_{S}^{0}D_{s}^{+}D^{*-} and e^{+}e^{-}→K_{S}^{0}D_{s}^{*+}D^{-}, as well as their charge conjugated processes, at five center-of-mass energies between 4.628 and 4.699 GeV, using data samples corresponding to an integrated luminosity of 3.8  fb^{-1} collected by the BESIII detector at the BEPCII storage ring. Based on a partial reconstruction technique, we find evidence of a structure near the thresholds for D_{s}^{+}D^{*-} and D_{s}^{*+}D^{-} production in the K_{S}^{0} recoil-mass spectrum, which we refer to as the Z_{cs}(3985)^{0}. Fitting with a Breit-Wigner line shape, we find the mass of the structure to be (3992.2±1.7±1.6)  MeV/c^{2} and the width to be (7.7_{-3.8}^{+4.1}±4.3)  MeV, where the first uncertainties are statistical and the second are systematic. The significance of the Z_{cs}(3985)^{0} signal is found to be 4.6σ including both the statistical and systematic uncertainty. We report the Born cross section multiplied by the branching fraction at different energy points. The mass of the Z_{cs}(3985)^{0} is close to that of the Z_{cs}(3985)^{+}. Assuming SU(3) symmetry, the cross section of the neutral channel is consistent with that of the charged one. Hence, we conclude that the Z_{cs}(3985)^{0} is the isospin partner of the Z_{cs}(3985)^{+}.

Using a data sample corresponding to an integrated luminosity of 11.3  fb^{-1} collected at center-of-mass energies from 4.23 to 4.70 GeV with the BESIII detector, we measure the product of the e^{+}e^{-}→π^{+}π^{-}ψ_{2}(3823) cross section and the branching fraction B[ψ_{2}(3823)→γχ_{c1}]. For the first time, resonance structure is observed in the cross section line shape of e^{+}e^{-}→π^{+}π^{-}ψ_{2}(3823) with significances exceeding 5σ. A fit to data with two coherent Breit-Wigner resonances modeling the sqrt[s]-dependent cross section yields M(R_{1})=4406.9±17.2±4.5  MeV/c^{2}, Γ(R_{1})=128.1±37.2±2.3  MeV, and M(R_{2})=4647.9±8.6±0.8  MeV/c^{2}, Γ(R_{2})=33.1±18.6±4.1  MeV. Though weakly disfavored by the data, a single resonance with M(R)=4417.5±26.2±3.5  MeV/c^{2}, Γ(R)=245±48±13  MeV is also possible to interpret data. This observation deepens our understanding of the nature of the vector charmoniumlike states. The mass of the ψ_{2}(3823) state is measured as (3823.12±0.43±0.13)  MeV/c^{2}, which is the most precise measurement to date.

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency., (© 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

As we all know, medical postgraduate education is very important for training high-quality clinicians, and can have a long-term impact on the promotion of the global health service system. In recent years, following the example of developed countries in Europe and America, the Chinese government has reformed the training mode of medical postgraduates and implemented the double tutor system. Although this system will bring many positive effects in theory, the difficulties encountered in implementing this system are real and need the joint efforts of schools, tutors and students to solve them. This article closely follows the background of the current era, compares the differences between Chinese and foreign graduate training modes, and emphatically discusses the significance and problems of the double tutor system in the postgraduate education reform in China., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Pulmonary hypertension (PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular (RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: non-invasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes., (© 2022 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Based on (10087±44)×10^{6}  J/ψ events collected with the BESIII detector, the process J/ψ→γπ^{+}π^{-}η^{'} is studied using two largest decay channels of the η^{'} meson, η^{'}→γπ^{+}π^{-} and η^{'}→ηπ^{+}π^{-}, η→γγ. A new resonance, which we denote as the X(2600), is observed with a statistical significance larger than 20σ in the π^{+}π^{-}η^{'} invariant mass spectrum, and it has a connection to a structure around 1.5  GeV/c^{2} in the π^{+}π^{-} invariant mass spectrum. A simultaneous fit on the π^{+}π^{-}η^{'} and π^{+}π^{-} invariant mass spectra with the two η^{'} decay modes indicates that the mass and width of the X(2600) state are 2618.3±2.0_{-1.4}^{+16.3}  MeV/c^{2} and 195±5_{-17}^{+26}  MeV, where the first uncertainties are statistical, and the second systematic.

Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1±8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3±10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P <0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH.

To determine whether glutamine consumption is associated with embryo quality and aneuploidy, a retrospective study was conducted in an in vitro fertilization center. Spent embryo culture media from patients undergoing assisted reproduction treatment and preimplantation genetic testing (PGT) were obtained on day 3 of in vitro culture. Embryo quality was assessed for cell number and fragmentation rate. PGT for aneuploidy was performed using whole genome amplification and DNA sequencing. Glutamine levels in spent embryo culture media were analyzed by gas chromatography-mass spectrometry. The results demonstrated that glutamine was a primary contributor to the classification of the good-quality and poor-quality embryos based on the orthogonal partial least-squares discriminant analysis model. Glutamine consumption in the poor-quality embryos was significantly higher than that in the good-quality embryos (P < 0.05). A significant increase in glutamine consumption was observed from aneuploid embryos compared with that from euploid embryos (P < 0.01). The Pearson correlation coefficients between embryo quality and glutamine consumption, and between aneuploidy and glutamine consumption, were 0.430 and 0.757, respectively. The area under the ROC curve was 0.938 (95% CI: 0.902-0.975) for identifying aneuploidy. Animal experiments demonstrate that increased glutamine consumption may be a compensatory mechanism to mitigate oxidative stress. Our data suggest that glutamine consumption is associated with embryo quality and aneuploidy. Glutamine may serve as a molecular indicator for embryo assessment and aneuploidy testing., (© 2022. The Author(s).)

O. elatus Nakai is a traditional medicine that has been confirmed to exert effective antioxidant and anti-inflammatory functions, and is used for the treatment of different disorders. However, its potential beneficial effects on drug induced hepatotoxicity and relevant molecular mechanisms remain unclear. This study investigated the protective effect and further elucidated the mechanisms of action of O. elatus on liver protection. O. elatus chlorogenic acids-enriched fraction (OEB), which included chlorogenic acid and isochlorogenic acid A, were identified by HPLC-MS/MS. OEB was administrated orally daily for seven consecutive days, followed by a single intraperitoneal injection of an overdose of APAP after the final OEB administration. The effects of OEB on immune cells in mice liver were analyzed using flow cytometry. APAP metabolite content in serum was detected using HPLC-MS/MS in order to investigate whether OEB affects CYP450 activities. The intestinal content samples were processed for 16 s microbiota sequencing. Results demonstrated that OEB decreased alanine aminotransferase, aspartate aminotransferase contents, affected the metabolism of APAP, and decreased the concentrates of APAP, APAP-CYS and APAP-NAC by inhibiting CYP2E1 and CYP3A11 activity. Furthermore, OEB pretreatment regulated lipid metabolism by affecting the peroxisome proliferator-activated receptors (PPAR) signaling pathway in mice and also increased the abundance of Akkermansia and Parabacteroides . This study indicated that OEB is a potential drug candidate for treating hepatotoxicity because of its ability to affect drug metabolism and regulate lipid metabolism., 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 Jiang, Luo, Zhou, Luo, Hao, Fan, Wu, Gao, Bi, Zhao, Lian and Lian.)

The aim of the present study was to analyze the high-quality blastocyst (HB) rate in all embryo frozen cycles and investigate the pregnancy outcomes for day 5/day 6 (D5/D6) blastocysts with respect to the blastocyst quality in programmed single vitrified-warmed blastocyst transfer (SVBT). We performed a retrospective study comparing D5/D6 HBs in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for all blastocyst frozen cycles. Patients were <35 years at the oocyte collection in their first fresh cycle without fresh transfer. A total of 1,560 IVF/ICSI cycles and 5,328 blastocysts were analyzed. The IVF HB rate was higher than that of ICSI (52.7% vs. 42.6%; P<0.05). The D5 HB rate was much higher than the D6 HB rate (61.6% vs. 29.4%; P<0.05). There were 22.4% (349/1,560) cycles that only had D6 blastocysts, of which IVF cycles were lower than ICSI (19.8% vs. 28.5%; P<0.05). The clinical pregnancy rate and implantation rate in the D5 group were significantly higher than these rates in the D6 group (57.4% vs. 46.2%, 58.9% vs. 47.3%; P<0.05). However, the clinical pregnancy rate and implantation rate of the D5 HBs were not significantly different from those of the D6 HBs (60% vs. 54.5%, 62% vs. 56.3%; P>0.05). In conclusion, the fertilization method (IVF/ICSI) directly influences the HB rate and blastocyst development rates. When we controlled for patient age, transfer frequency, and endometrium on day 5, it was not the development stage (D5/D6), rather the transfer blastocyst quality that played an important role in pregnancy outcomes., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Jiang et al.)

The purpose of this cross-sectional study is to determine the association between yogurt consumption and lipid profiles in the general Chinese population. In this cross-sectional study, a total of 26,824 participants were included from Tianjin, China. Lipid profiles were determined by automated biochemical analyser. Yogurt consumption frequency was assessed by a validated food frequency questionnaire. Analysis of covariance was used to determine the association between daily yogurt consumption and lipid profiles. In the final multivariate model, daily yogurt consumption was negatively associated with triglyceride (TG) ( p for trend <0.001) and positively associated with high density lipoprotein cholesterol (HDL-C) ( p for trend = 0.02). There were no significant differences ( p for trend >0.05) between daily yogurt consumption and total cholesterol (TC) or low density lipoprotein cholesterol (LDL-C). Results suggested that higher daily yogurt consumption was negatively correlated with TG and positively correlated with HDL-C in the general Chinese population.

Intravesical administration of first-line drugs has shown failure in the treatment of bladder cancer owing to the poor tumor retention time of chemotherapeutics. Herein, we report an intracellular hydrolytic condensation (IHC) system to construct long-term retentive nano-drug depots in situ, wherein sustained drug release results in highly efficient suppression of bladder cancer. Briefly, the designed doxorubicin (Dox)-silane conjugates self-assemble into silane-based prodrug nanoparticles, which condense into silicon particle-based nano-drug depots inside tumor cells. Significantly, we demonstrate that the IHC system possesses highly potent antitumor efficacy, which leads to the regression and eradication of large established tumors and simultaneously extends the overall survival of air pouch bladder cancer mice compared with that of mice treated with Dox. The concept of intracellular hydrolytic condensation can be extended via conjugating other chemotherapeutic drugs, which may facilitate rational design of novel nanomedicines for augmentation of chemotherapy., (© 2022 Wiley-VCH GmbH.)

The singly Cabibbo-suppressed decay Λ&#95;{c}^{+}→nπ^{+} is observed for the first time with a statistical significance of 7.3σ by using 3.9  fb^{-1} of e^{+}e^{-} collision data collected at center-of-mass energies between 4.612 and 4.699 GeV with the BESIII detector at BEPCII. The branching fraction of Λ&#95;{c}^{+}→nπ^{+} is measured to be (6.6±1.2&#95;{stat}±0.4&#95;{syst})×10^{-4}. By taking the upper limit of branching fractions of Λ&#95;{c}^{+}→pπ^{0} from the Belle experiment, the ratio of branching fractions between Λ&#95;{c}^{+}→nπ^{+} and Λ&#95;{c}^{+}→pπ^{0} is calculated to be larger than 7.2 at the 90% confidence level, which disagrees with most predictions of the available phenomenological models. In addition, the branching fractions of the Cabibbo-favored decays Λ&#95;{c}^{+}→Λπ^{+} and Λ&#95;{c}^{+}→Σ^{0}π^{+} are measured to be (1.31±0.08&#95;{stat}±0.05&#95;{syst})×10^{-2} and (1.22±0.08&#95;{stat}±0.07&#95;{syst})×10^{-2}, respectively, which are consistent with previous results.

We report here the purification of a novel metal-binding protein from Oratosquilla oratoria ( O. oratoria MT-1) by gel and ion-exchange chromatography. SDS-PAGE and MALDI-TOF analyses demonstrated that isolated O. oratoria MT-1 was of high purity with a molecular weight of 12.4 kDa. The fluorescence response to SBD-F derivatives revealed that O. oratoria MT-1 contained a large number of sulfhydryl groups, which is a general property of metallothioneins. Zn and Cu metal stoichiometries for O. oratoria MT-1 were 3.97:1 and 0.55:1, respectively. The proportion of cysteine (Cys) residues in the amino acid composition was 32.69%, and aromatic amino acids were absent. The peptide sequence coverage with Macrobrachium rosenbergii calmodulin (accession AOA3S8FSK5) was 60%. Infrared spectroscopy of O. oratoria MT-1 revealed two obvious peaks at absorption frequencies for the amide I band and the amide II band. CD spectra revealed that the secondary structure was mainly composed of random coil (57.6%) and β-sheet (39.9%). An evaluation of in vitro antioxidant activity revealed that isolated O. oratoria MT-1 has strong reducing activities, exhibiting scavenging rates for DPPH and OH of 77.8% and 75.8%, respectively (IC 50 values 0.57 mg/mL and 1.1 mg/mL). O. oratoria MT-1 may be used as a functional additive in cosmetics, health foods, and medical products, as well as a reference material for quantitative analysis of metallothionein in such products.

Subgroup J Avian leukosis virus (ALV-J) is an important pathogen of poultry tumor diseases. Since its discovery, it has caused significant economic losses to the poultry industry. Thus, the rapid detection of molecular level with strong specificity is particularly important whether poultry are infected with ALV-J. In this study, we designed primers and probe for real-time fluorescent reverse-transcription recombinase-aided amplification assay (RT-RAA) based on the ALV-J gp85 sequence. We had established a real-time fluorescent RT-RAA method and confirmed this system by verifying the specificity and sensitivity of the primers and probe. In addition, repeatability tests and clinical sample regression tests were used for preliminary evaluation of this detection method. The sensitivity of established method was about 10 1 copies/μL, and the repeatability of the CV of the C T value is 4%, indicating repeatability is good. Moreover, there was no cross-reactivity with NDV, IBV, IBDV, H9N2, MDV, and REV, and other avian leukosis virus subgroups, such as subgroups A, B, C, D, K and E. Importantly, the real-time fluorescent RT-RAA completed the test within 30 min at a constant temperature of 41°C. Forty-two clinical samples with known background were tested, and the test results were coincided with 100%. Overall, these results suggested that the real-time fluorescent RT-RAA developed in this study had strong specificity, high sensitivity, and good feasibility. The method is simple, easy, and portable, that is suitable for clinical and laboratory diagnosis, and provides technical support for the prevention and control of ALV-J., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is associated with high mortality and disability, with a substantial socioeconomic burden. With the standardization of the treatment process, there is increasing interest in the role that the secondary insult of TBI plays in outcome heterogeneity. The secondary insult is neither detrimental nor beneficial in an absolute sense, among which the inflammatory response was a complex cascade of events and can thus be regarded as a double-edged sword. Therefore, clinicians should take the generation and balance of neuroinflammation following TBI seriously. In this review, we summarize the current human and animal model studies of neuroinflammation and provide a better understanding of the inflammatory response in the different stages of TBI. In particular, advances in neuroinflammation using proteomic and transcriptomic techniques have enabled us to identify a functional specific delineation of the immune cell in TBI patients. Based on recent advances in our understanding of immune cell activation, we present the difference between diffuse axonal injury and focal brain injury. In addition, we give a figurative profiling of the general paradigm in the pre- and post-injury inflammatory settings employing a bow-tie framework., 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 Zheng, Lee, Qi, Wang, Xu, Wu and Mao.)

Background: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD)., Methods: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212)., Findings: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 μg group, three (15%) of 20 in the 10 μg group, six (30%) of 20 in the 15 μg group, seven (35%) of 20 in the 20 μg group, five (31%) of 16 in the 25 μg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19., Interpretation: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale., Funding: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences., Competing Interests: C-FQ and BY are co-inventors on pending patent applications related to the ARCoV mRNA vaccine. LW is an employee of Suzhou Abogen Biosciences. S-YY and ZH are employees of Walvax. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Objective: To analyze the dynamic changes of schistosomiasis in Poyang County of Jiangxi Province from 2004 to 2020, so as to provide insight into the development of the schistosomiasis elimination strategy., Methods: Schistosomiasis control data were captured from Poyang County from 2004 to 2020, and the epidemiological data of schistosomiasis were collected from national schistosomiasis surveillance sites in Poyang County from 2005 to 2020. The endemic status of schistosomiasis was analyzed in Poyang County from 2004 to 2020, and a Joinpoint regression analysis was performed to investigate the trends of schistosomiasis in Poyang County from 2004 to 2020., Results: The sero-prevalence and egg-prevalence of human Schistosoma japonicum infections reduced from 24.39% (24 976/102 397) and 4.53% (259/5 721) in 2004 to 5.37% (2 421/45 100) [annual percent change (APC) = average annual percent change (AAPC) = -8.64%] and 0 (0/3 963) in 2020 (APC = AAPC = -32.07%) in Poyang County, and the trends were both significant (both P < 0.01). The sero-prevalence of S. japonicum infections reduced from 1.21% (294/24 332) in bovines in 2013 to 0.58% (35/5 999) in 2020 in Poyang County, with one turning point (AAPC = -8.20%, P > 0.05). There were no townships or villages with emerging snail habitats in Poyang County from 2004 to 2020, and there were three turning points of trend in the proportion of snail areas detected in total snail areas (AAPC = -2.30%, P > 0.01). The sero-prevalence and adjusted prevalence of S. japonicum infections reduced from 60.82% (742/1 220) and 10.16% (124/1 220) in local residents in 2005 to 5.73% (70/1 221) and 0 in 2020 in national schistosomiasis surveillance sites of Poyang County, and the trends for sero-prevalence (APC = AAPC = 17.47%, P < 0.01) and adjusted prevalence of S. japonicum infections (APC = AAPC = -44.92%, P < 0.01) were both statistically significant. S. japonicum infections were identified in 10 (2005) and 2 local livestock (2007), with prevalence of 10.00% (10/100) and 13.33% (2/15), respectively, and S. japonicum infections were detected in snails in 2008 and 2009; however, no positive samples of mixed O. hupensis were detected by loop-mediated isothermal amplification., Conclusions: The endemic situation of schistosomiasis control had remarkably reduced in Poyang County from 2004 to 2020; however, there are still challenges for consolidating schistosomiasis control achievements and even elimination of schistosomiasis.

Seaweeds have numerous biologically active ingredients, such as polysaccharides, polyphenols and carotenoids, that are beneficial to human health. Although these benefits might be related to the synthesis, secretion or reabsorption of uric acid, no studies have explored the relationship between seaweeds consumption and hyperuricaemia (HUA) in the general population. The aim of this study was to investigate whether seaweeds consumption is related to HUA in a large-scale adult population. A cross-sectional study was conducted with 32 365 adults (17 328 men and 15 037 women) in Tianjin, People's Republic of China. Frequency of seaweeds consumption was assessed by a validated self-administered FFQ. HUA was defined as serum uric acid levels >420 μmol/L in men and >350 μmol/L in women. The association between seaweeds consumption and HUA was assessed by multiple logistic regression analysis. Restricted cubic spline functions were used for non-linearity tests. The prevalence of HUA in men and women was 21·17 % and 5·93 %, respectively. After adjustments for potential confounding factors, the OR (95 % CI) for HUA across seaweed consumption (g/1000 kcal per d) were 1·00 (reference) for level 1, 0·91 (95 % CI 0·81, 1·02) for level 2; 0·90 (95 % CI 0·81, 1·01) for level 3; 0·86 (95 % CI 0·78, 0·97) for level 4 in men and 0·90 (95 % CI 0·73, 1·10) for level 2; 0·82 (95 % CI 0·67, 1·00) for level 3; 0·84 (95 % CI 0·68, 1·03) for level 4 in women, respectively. A negative correlation between seaweeds consumption and HUA in males but not in females was observed. Further studies are needed to explore the causal relationship.

Based on electron-positron collision data collected with the BESIII detector operating at the Beijing Electron-Positron Collider II storage rings, the value of R≡σ(e^{+}e^{-}→hadrons)/σ(e^{+}e^{-}→μ^{+}μ^{-}) is measured at 14 center-of-mass energies from 2.2324 to 3.6710 GeV. The resulting uncertainties are less than 3.0% and are dominated by systematic uncertainties.

Purpose: To explore the feasibility and safety of centrally located hepatocellular carcinoma (CL-HCC) treated by narrow-margin resection combined with intraoperative electron radiotherapy (IOERT)., Methods and Materials: From November 2009 to November 2016, 37 consecutive patients were treated with IOERT as adjuvant treatment during narrow-margin resection for CL-HCC. Long-term outcomes, adverse events for surgery, and acute and chronic toxicities were analyzed., Results: The median follow-up was 57.82 months (range, 3.75-111.41 months). A total dose of 15 Gy (range 12 to 17Gy) (prescribed at the 90% isodose) was delivered with a 0.9cm (range 0.8-1.2 cm) median treatment depth targeting the narrow-margin. The 1-year, 3-year and 5-year OS rates were 91.39%, 88.34% and 88.34%, respectively. The 1-year, 3-year and 5-year DFS rates were 80.81%, 68.59% and 54.17%, respectively. In the univariate analysis, none of the treatment characteristics were predictive of overall survival. Fifteen (40.5%) patients suffered from a recurrence event. No patient had marginal recurrence. The 1-year, 3-year and 5-year intrahepatic recurrence rates were 19.75%, 25.92% and 39.58%, respectively. The 1-year, 3-year and 5-year extrahepatic recurrence rates were 2.7%, 5.95% and 9.87%, respectively. There was no 30-day surgical-related death. Three patients had grade 4, and 28 patients had grade 3 alanine aminotransferase (ALT) levels, and seven patients had grade 4, and 30 patients had grade 3 aspartate transaminase (AST) levels. All of them returned to normal within four months. There was no acute radiation-induced liver injury during follow-up. There were no acute or chronic toxicities associated with IOERT., Conclusion: IOERT for narrow-margin CL-HCC may achieve good long-term survival outcomes, without significantly increasing acute and chronic toxicities. An IOERT dose of 15Gy may be the safest and most feasible. IOERT might be considered as an adjuvant therapy for CL-HCC patients with a narrow-margin., 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 Wu, Zhai, Li, Cai, Ma, Wang, Wu, Wang, Wu, Zeng, Chen, Li, Wu and Feng.)

The rapid identification of bacterial antibiotic susceptibility is pivotal to the rational administration of antibacterial drugs. In this study, cefotaxime (CTX)-derived resistance in Salmonella typhimurium (abbr. CTX r - S. typhimurium ) during 3 months of exposure was rapidly recorded using a portable Raman spectrometer. The molecular changes that occurred in the drug-resistant strains were sensitively monitored in whole cells by label-free surface-enhanced Raman scattering (SERS). Various degrees of resistant strains could be accurately discriminated by applying multivariate statistical analyses to bacterial SERS profiles. Minimum inhibitory concentration (MIC) values showed a positive linear correlation with the relative Raman intensities of I 990 / I 1348 , and the R 2 reached 0.9962. The SERS results were consistent with the data obtained by MIC assays, mutant prevention concentration (MPC) determinations, and Kirby-Bauer antibiotic susceptibility tests (K-B tests). This preliminary proof-of-concept study indicates the high potential of the SERS method to supplement the time-consuming conventional method and help alleviate the challenges of antibiotic resistance in clinical therapy.

Background: Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. In China, it is the most common cancer in the female genital tract. However, the genomic profiles of Chinese cervical cancer patients remain unclear., Materials and Methods: A total of 129 cervical cancer patients were enrolled in this study (113 squamous, 12 adenocarcinoma, 2 adenosquamous, and 2 neuroendocrine carcinoma). To classify the clinical features and molecular characteristics of cervical cancer, the genomic alterations of 618 selected genes were analyzed in the samples of these patients, utilizing target next-generation sequencing (NGS) technology. Furthermore, the findings from the Chinese cohort were then compared with the data of Western patients downloaded from The Cancer Genome Atlas (TCGA) database, in terms of gene expression files, mutation data, and clinical information., Results: All studied patients had valid somatic gene alterations, and the most frequently altered genes were PIK3C , TP53 , FBXW7 , ARID1A , ERBB2 , and PTEN . Comparison of genomic profiling showed significantly different prevalence of genes, including TP53, KMT2C , and RET , between the Chinese and the TCGA cohorts. Moreover, 57 patients (44.19%) with 83 actionable alterations were identified in our cohort, especially in PI3K and DNA damage repair (DDR) pathways. After an in-depth analysis of cervical cancer data from the TCGA cohort, DDR alteration was found to be associated with extremely higher tumor mutation burden (TMB) (median mutation count: 149.5 vs 66, p <0.0001), and advanced stages (p <0.05). Additionally, DDR alteration, regardless of its function, was positively correlated with hypoxia feature and score. Moreover, patients with a high hypoxia score were positively correlated with a high abundance of mast cell resting, but lower abundance of CD8+ T cells and activated mast cell. Finally, CDHR5 was identified as the hub gene to be involved in the DDR-hypoxia network, which was negatively correlated with both the DDR alteration and hypoxia score., Conclusions: Overall, a unique genomic profiling of Chinese patients with cervical cancer was uncovered. Besides, the prevalent actionable variants, especially in PI3K and DDR pathways, would help promote the clinical management. Moreover, DDR alteration exerted the significant influence on the tumor microenvironment in cervical cancer, which could guide the clinical decisions for the treatment. CDHR5 was the first identified hub gene to be negatively correlated with DDR or hypoxia in cervical cancer, which had potential effects on the treatment of immune checkpoint inhibitors (ICIs)., 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 Wen, Guo, Zhou, Wu and Li.)

A promising anode material consisting of bimetallic thiophosphate Zn x Co 1- x PS 3 and CoS 2 with 2D/3D heterostructure is designed and prepared by an effective chemical transformation. Density functional theory calculations illustrate that the Zn 2+ can effectively modulate the electrical ordering of Zn x Co 1- x PS 3 on the nanoscale: the reduced charge distribution emerging around the Zn ions can enhance the local built-in electric field, which will accelerate the ions migration rate by Coulomb forces and provide tempting opportunities for manipulating Li + storage behavior. Moreover, the merits of the large planar size enable Zn x Co 1- x PS 3 to provide abundant anchoring sites for metallic CoS 2 nanocubes, generating a 2D/3D heterostructure with a strong electric field. The resultant Zn x Co 1- x PS 3 /CoS 2 can offer the combined advantages of bimetallic alloying and heterostructure in lithium storage applications, leading to outstanding performance as an anode material for lithium-ion batteries. Consequently, a high capacity of 794 mA h g -1 can be retained after 100 cycles at 0.2 A g -1 . Even at 3.0 A g -1 , a satisfactory capacity of 465 mA h g -1 can be delivered. The appealing alloying-heterostructure and electrochemical performance of this bimetallic thiophosphate demonstrate its great promise for applications in practical rechargeable batteries., (© 2021 Wiley-VCH GmbH.)

Materials with superhydrophobic surfaces have received vast attention in various industries due to their valuable properties, such as their self-cleaning and antifouling effects. These promising superhydrophobic properties are taken into high priority, particularly for medical devices and applications. The development of an ideal superhydrophobic surface is a challenging task and is constantly progressing. Various strategies have been introduced; however, a minority of them are cost-effective. This work presents a facile fabrication of the superhydrophobic surface by using graphene and titanium dioxide (TiO 2 ) nanoparticles. The graphene and TiO 2 hybrid nanoparticles are dip-coated on a biodegradable thermoplastic poly(lactic acid) (PLA) substrate. The thermoplastic PLA is approved by the Food and Drug Administration (FDA), and is widely utilized in medical devices. The graphene/TiO 2 coating is substantiated to transform the hydrophilic PLA film into superhydrophobic biomaterials that can help to reduce hazardous medical-device complications. The surface wettability of the graphene/TiO 2 nanoparticle-coated PLA surface was evaluated by measuring the apparent water contact angle. The surface chemical composition and surface morphology were analyzed via Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The graphene/TiO 2 -coated PLA film achieved superhydrophobic properties by demonstrating a water contact angle greater than 150°. The water contact angle of the graphene/TiO 2 coating increased along with the concentration of the nanoparticles and the ratio of TiO 2 to graphene. Moreover, the graphene/TiO 2 coating exhibited excellent durability, whereby the contact angle of the coated surface remained unchanged after water immersion for 24 h. The duration of the effectiveness of the superhydrophobic coating suggests its suitability for medical devices, for which a short duration of administration is involved. This study reports an easy-to-replicate and cost-effective method for fabricating superhydrophobic graphene/TiO 2 -coated surfaces, which additionally substantiates a potential solution for the manufacturing of biomaterials in the future.

Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues. However, the application of these fluorescence contrast agents in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) was dramatically hammered as a result of lacking active targeting and poor retention time in tumor, which limited the Signal to Noise Ratio (SNR) and narrowed the imaging window for complicated surgery. Herein, we reported an activated excretion-retarded tumor imaging ( AERTI ) strategy, which could be in situ activated with MMP-2 and self-assembled on the surface of tumor cells, thereby resulting in a promoted excretion-retarded effect with an extended tumor retention time and enhanced SNR. Briefly, the AERTI strategy could selectively recognize the Integrin α v β 3 . Afterwards, the AERTI strategy would be activated and in situ assembled into nanofibrillar structure after specifically cleaved by MMP-2 upregulated in a variety of human tumors. We demonstrated that the AERTI strategy was successfully accumulated at the tumor sites in the 786-O and HepG2 xenograft models. More importantly, the modified modular design strategy obviously enhanced the SNR of AERTI strategy in the imaging of orthotopic RCC and HCC. Taken together, the results presented here undoubtedly confirmed the design and advantage of this AERTI strategy for the imaging of tumors in metabolic organs., (© 2021 The Authors.)

Slow transit constipation (STC) is a common type of constipation with a high incidence rate and a large number of patients. We aimed to investigate the therapeutic effects and potential mechanism of paeoniflorin (PAE) on loperamide-induced Sprague Dawley (SD) rat constipation models. Rats with loperamide-induced constipation were orally administered different concentrations of PAE (10, 20, or 40 mg/kg). In vitro, enterochromaffin (EC)-like RIN-14B cells were treated with 20, 40, or 80  μ g/ml PAE. We found that PAE treatment significantly improved the symptoms of constipation and increased the intestinal transit rate. Hematoxylin and eosin (H&E) staining showed that PAE alleviated colonic tissue pathological damage. Besides, our results implied that PAE concentration-dependently promoted the content of 5-hydroxytryptamine (5-HT) catalyzed by tryptophan hydroxylase (Tph)-1 in the serum of loperamide-induced rats and in RIN-14B cells. Western blot and immunofluorescence (IF) stain indicated that PAE also promoted the expression of G protein-coupled BA receptor 1 (TGR5), transient receptor potential ankyrin 1 (TRPA1), phospholipase C (PLC)- γ 1, and phosphatidylinositol 4,5-bisphosphate (PIP2) in vivo and in vitro . RIN-14B cells were cotreated with a TGR5 inhibitor (SBI-115) to explore the mechanism of PAE in regulating the 5-HT secretion. We observed inhibition of TGR5 reversed the increase of 5-HT secretion induced by PAE in RIN-14B cells. We provided evidence that PAE could promote 5-HT release from EC cells and improve constipation by activating the TRPA1 channel and PLC- γ 1/PIP2 signaling. Thus, PAE may provide therapeutic effects for patients with STC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yu Zhan et al.)

The fabrication of solid-state single-molecule switches with high on-off conductance ratios has been proposed to advance conventional technology in areas such as molecular electronics. Herein, we employed the scanning tunneling microscope break junction (STM-BJ) technique to modulate conductance in single-molecule junctions using mechanically induced stretching. Compound 1a possesses two dihydrobenzothiophene (DHBT) anchoring groups at the opposite ends linked with rigid alkyne side arms to form a gold-molecule-gold junction, while 1b contains 4-pyridine-anchoring groups. The incorporation of ferrocene into the backbone of each compound allows rotational freedom to the cyclopentadienyl (Cp) rings to give two distinct conductance states (high and low) for each. Various control experiments and suspended junction compression/retraction measurements indicate that these high- and low-conductance plateaus are the results of conformational changes within the junctions (extended and folded states) brought about by mechanically induced stretching. A high-low switching factor of 42 was achieved for 1a , whereas an exceptional conductance ratio in excess of 2 orders of magnitude (205) was observed for 1b . To the best of our knowledge, this is the highest experimental on-off conductance switching ratio for a single-molecule junction exploiting the mechanically induced STM-BJ method. Computational studies indicated that the two disparate conductance states observed for 1a and 1b result from mechanically induced conformational changes due to an interplay between conductance and the dihedral angles associated with the electrode-molecule interfaces. Our study reveals the structure-function relationship that determines conductance in such flexible and dynamic systems and promotes the development of a single-molecule variable resistor with high on-off switching factors.

Background/objectives: High plain water intake (PWI) lowered body weight, reduced total energy intake, and increased fat oxidation and energy consumption. Because such factors are closely linked to metabolic disorders, which are the main risk factors for nonalcoholic fatty liver disease (NAFLD) onset, it was speculated that higher PWI was associated with a lower risk of NAFLD. However, no prior human studies have examined such relationship. Therefore, the purpose of this study was to evaluate the relationship between PWI and newly diagnosed NAFLD in a large-scale adult population., Subjects/methods: A total of 16,434 participants from 2010 to 2019 in Tianjin, China, were included in this cross-sectional study. PWI was assessed by using a validated self-administered food frequency questionnaire, and it was categorized into three subgroups for analysis: ≤3 cups/day, 4-7 cups/day, and >7 cups/day. NAFLD was diagnosed by abdominal ultrasound. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationship between PWI and NAFLD., Results: Among 16,434 participants, 20.5% (3,364) had newly diagnosed NAFLD. After controlling for demographic characteristics, lifestyle risk factors, and dietary intake, the adjusted ORs (95% CIs) for having NAFLD across PWI categories were 1.00 (reference) for ≤3 cups/day, 0.84 (0.72, 0.97) for 4-7 cups/day, and 0.77 (0.63, 0.94) for >7 cups/day in males and 1.00 (reference) for ≤3 cups/day, 1.02 (0.81, 1.27) for 4-7 cups/day, and 1.08 (0.78, 1.49) for >7 cups/day in females, respectively., Conclusions: This study is the first to show that higher PWI is independently related to lower newly diagnosed NAFLD among males, but not females. Further studies are needed to explore the causal relationship., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: To investigate the potential differences between topography-guided (TG) and wavefront-optimized (WFO) laser in situ keratomileusis (LASIK) for the treatment of myopia., Methods: A systematic literature search was performed to determine relevant trials comparing LASIK with TG and WFO from the time of library construction to August 2020, and The PubMed, Cochrane, Web of Science, EMBASE and Chinese databases ( i.e. CNKI, CBM, WAN FANG and VIP) were accessed. The data on visual acuity, refractive status and wavefront aberration were retrieved and evaluated from three to six months after surgery. STATA (version 14.0) software was used for statistical analysis. A cumulative Meta-analysis was simultaneously performed., Results: Eleven studies with a total of 1425 eyes were incorporated. No statistically significant differences were evident between TG and WFO ablation in the proportion of eyes achieving an uncorrected distance visual acuity (UCVA) of 20/20 or better ( P =0.377), gaining one line or more ( P =0.05), postoperative cylinder ( P =0.40), vertical coma ( P =0.593) and horizontal coma ( P =0.957). After TG ablation, the proportion of the patients' eyes of which postoperative refraction is within ±0.5 diopter of the target refraction was significantly higher than that undergoes WFO ( P =0.003). As opposed to the WFO group, manifest refraction spherical equivalent (MRSE; P =0.000) was lower, and UCVA ( P =0.005) was better in the TG group. The higher-order aberrations (HOAs; P =0.000), spherical aberration ( P =0.000) and coma ( P =0.000) were significantly lower in TG group. The cumulative Meta-analysis illustrated that the proportion of eyes achieving UCVA of 20/20 or better, postoperative refraction within ±0.5 diopter, and MRSE has steady between the two groups., Conclusion: Both TG-LASIK and WFO-LASIK are safe, effective, and predictable for correcting myopia. TG-LASIK may produce fewer aberration and is more precise than WFO-LASIK., (International Journal of Ophthalmology Press.)

ZnS/carbon nanocomposites have potential electrochemical applications due to their improved conductivity and more active sites through modification of the carbon materials. Herein, we report a facile method to synthesize the nanocomposites comprising ZnS nanoparticles and nitrogen-doped carbon (ZnS@NC). The inorganic-organic hybrid ZnS-amine material ZnS(ba) (ba = n -butylamine) is synthesized on a large scale by a reflux method, which effectively shortens the reaction time while maintaining the high yield compared with the solvothermal method. Then ZnS(ba) is used as precursor for obtaining ZnS@NC nanocomposites via a vacuum pyrolysis route, in which the content of carbon and nitrogen can be controlled by adjusting the pyrolysis temperature. Further, a series of ZnS-amine hybrid materials ZnS(ha), ZnS(en) 0.5 and ZnS(pda) 0.5 (ha = n -hexylamine; en = ethylenediamine; pda = 1,3-propanediamine) are synthesized and used as precursors for the preparation of ZnS@NC materials, indicating the universality of this method. Moreover, the as-synthesized ZnS@NC materials exhibit remarkable lithium storage performance with outstanding cycling stability, high-rate capability and remarkable pseudo-capacitance characteristics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The exploration of advanced anode materials through rational structure/phase design is the key to developing high-performance rechargeable batteries. Herein, tetraphosphorus tetraselenide (Se 4 P 4 ) nanoparticles confined within porous carbon (named SeP@C) are developed for lithium-ion batteries. The designed SeP@C shows a set of structural/compositional advantages as lithium-ion battery anodes including high electrical conductivity, low ion diffusion barrier, and relieved lithiation stress. Consequently, the SeP@C electrode displays superior comprehensive lithium storage performance, e.g., high reversible capacity (640.8 mA h g -1 at 0.1 A g -1 ), excellent cycling stability (500 cycles with respective capacity retention of over or nearly 100%), and good rate capability, representing a comparable lithium storage performance in reported phosphide-based anodes. More significantly, it shows excellent energy storage properties in lithium-ion full cells which can light up 85 red LEDs for over 3.2 h. This work offers an advanced electrode construction guidance of phosphorous-based anodes for the development of high-performance energy storage devices., (© 2021 IOP Publishing Ltd.)

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a rare and chronic progressive clinical entity, characterized by elevated serum IgG4 along with tissue infiltration by IgG4 + plasma cells. It is an immune-mediated fibro-inflammatory condition that can affect virtually any organ and tissue. IgG4-related lung disease (IgG4-RLD) occupies 14% of all IgG4-RD, with nonspecific symptoms and various abnormal radiographic patterns. Published data on IgG4-related hypertrophic pachymeningitis (IgG4-RHP), an increasingly recognized central nervous system manifestation of IgG4-RD, is also limited. Both lung and cranial dura involvement have not yet been reported until now. We further entail a review of the literature on the clinicopathologic features and differential diagnosis of this uncommon disease. We herein report an interesting case of a 70-year-old male patient admitted due to headache and fever. A magnetic resonance imaging (MRI) of the brain revealed extensive dural thickening with marked enhancement. Chest computed tomography (CT) scan showed nodular or mass-like consolidation and focal interstitial change. Thoracoscopic lung biopsy and lumbar puncture were conducted. After careful histopathological observation and consideration of alternative differential diagnoses, he was diagnosed with IgG4-related disease with lung and cranial dural involvement based upon significant elevation of serum and cerebrospinal fluid (CSF) IgG4 concentration. The patient was started on oral prednisolone 60 mg/day (1.0 mg/kg/day) for 14 days, and a tapering dose of 5 mg every 2 weeks followed by maintenance therapy at low dose for 3 months. His clinical manifestations, and serologic and imaging findings improved with steroid treatment. Currently, the patient remains well without disease progression. IgG4-RD should be considered as a differential when diagnosing other similar multisystemic lesions. Clinical examination, careful histological observation, and immunostaining for appropriate markers are essential in establishing the diagnosis. Clinicians should become familiar with this alternative differential diagnosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Soil bacteria play a key role in the plant-soil system and can regulate the growth of Phoebe bournei seedlings under fertilization. However, there are few reports on how soil bacteria respond to fertilization and regulate seedling growth. This study adopted the "3414" field fertilization experiment, combined with soil microbial sequencing, nutrient contents, and biomass measurement, to explore the changes of soil chemical properties and bacterial structure under different NPK fertilization conditions and to establish the coupling relationship between soil bacteria, soil nutrients, and plant growth. The results showed that NPK fertilization decreased soil pH; increased soil N, P, and K content; reduced bacterial diversity and abundance; promoted the growth of dominant bacterial species; and enhanced Phoebe bournei seedlings' soil N, P, and K elements. NPK fertilization promoted Proteobacteria growth, especially of three genera ( Methylobacterium , Sphingobium , and Acinetobacter ) and Actinobacteria, while it decreased Acidobacteria and Chloroflexi. By reducing the ratio of N to K and increasing P, NPK fertilization can slow soil acidification, promote bacterial reproduction, maintain P. bournei seedlings' soil ecological stability, and balance the seedlings' growth and sustainable soil utilization. AD3 , Pseudomonas , and Rhodanobacter can be used as the marker species for N, P, and K fertilization, respectively, while Methylobacterium , Brevundimonas , Acinetobacter , and Sphingobium can be used as indicator species for soil pH and soil N, P, and K content changes, respectively. These results provided a theoretical basis and technical guidance for the effective fertilization and cultivation of robust P. bournei seedlings.

Long noncoding RNAs are a group of more than 200 nt, nonprotein coding RNAs, some of which are dysregulated in many pathophysiological processes including endometriosis. This study aims to clarify the roles of dysregulated growth arrest-specific 5 (GAS5) in patients with endometriosis, and unveil the underlying mechanisms. We obtained endometrium samples from 37 patients with endometriosis and 23 controls without endometriosis. Primary endometrial stromal cells (ESCs) and endothelial cells were separated from the endometrium. Levels of GAS5 were quantified using quantitative real-time polymerase chain reaction, and levels of p27, cleaved caspase-3, cleaved poly (ADP-Ribose) polymerase 1, vascular endothelial growth factor A, tissue inhibitor of metalloproteinases 3 (TIMP3), and trypsin-modified soy protein 10 were assessed by immunoblotting. Cell viability was examined using MTT assays, and the cell cycle and apoptosis were analyzed by flow cytometry. Endothelial cell tube formation capacity was assayed in vitro. GAS5 and p27 levels were found lower in the endometrium samples from patients with endometriosis. Primary ESCs from patients with endometriosis had increased viability, reduced apoptosis, and a relatively uncontrolled cell cycle. Gain- and loss-of-function studies confirmed that GAS5 regulated p27 expression in ESCs. Furthermore, GAS5 level was relatively low in primary endothelial cells from patients with endometriosis and GAS5 acted as an angiogenesis inhibitor by regulating the miR-181c-TIMP3 axis. Thus, lower GAS5 level in endometrium might be related to endometriosis by regulating cell proliferation, apoptosis, cell cycle, and angiogenesis., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Objective: Our objective was to investigate the management of patients with asymptomatic suspicious thyroid nodules ≤1 cm., Methods: We retrospectively reviewed medical records of patients with sonographically suspicious thyroid nodules ≤1 cm and without distant metastases, suspicious lymph node metastasis (LNM), or extrathyroidal extension (ETE)., Results: Of the 386 enrolled patients, 174 (45.1%) had immediate surgery (IS), while 212 (54.9%) underwent active surveillance (AS). In the IS group, 166 (95.4%) patients were confirmed as having papillary thyroid microcarcinoma. LNM and ETE were observed in 24.7% and 2.4% cases, respectively. In the AS group, nodule size increased by ≥3 mm in 11 (5.2%) patients and 39 (18.4%) had a >50% increase in nodule volume after a median follow-up of 12 months. Nodules with smaller volume at diagnosis were more likely to increase in volume later. Newly suspicious LNM was detected in 23 (10.8%) patients. Delayed surgery (DS) was performed in 101 patients, with 27 showing disease progression. ETE and LNM were detected in 3% and 36%, respectively, of patients with papillary thyroid microcarcinoma. Compared with IS, tumors in the DS group more frequently showed lateral LNM and capsular invasion (P < .05). No patient had recurrence or died of thyroid cancer during postoperative follow-up (median 26 [4-60] months)., Conclusions: IS or DS of patients with asymptomatic suspicious thyroid nodules ≤1 cm was relatively high in China. The inertia of low-risk nodules and the effectiveness of DS for those that progressed make AS a feasible strategy., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)

Bama minipig is a unique miniature swine bred from China. Their favorable characteristics include delicious meat, strong adaptability, tolerance to rough feed, and high levels of stress tolerance. Unfavorable characteristics are their low lean meat percentage, high fat content, slow growth rate, and low feed conversion ratio. Genome-editing technology using CRISPR/Cas9 efficiently knocked out the myostatin gene (MSTN) that has a negative regulatory effect on muscle production, effectively promoting pig muscle growth and increasing lean meat percentage of the pigs. However, CRISPR/Cas9 genome editing technology is based on random mutations implemented by DNA double-strand breaks, which may trigger genomic off-target effects and chromosomal rearrangements. The application of CRISPR/Cas9 to improve economic traits in pigs has raised biosafety concerns. Base editor (BE) developed based on CRISPR/Cas9 such as cytosine base editor (CBE) effectively achieve targeted modification of a single base without relying on DNA double-strand breaks. Hence, the method has greater safety in the genetic improvement of pigs. The aim of the present study is to utilize a modified CBE to generate MSTN-knockout cells of Bama minipigs. Our results showed that the constructed "all-in-one"-modified CBE plasmid achieved directional conversion of a single C·G base pair to a T·A base pair of the MSTN target in Bama miniature pig fibroblast cells. We successfully constructed multiple single-cell colonies of Bama minipigs fibroblast cells carrying the MSTN premature termination and verified that there were no genomic off-target effects detected. This study provides a foundation for further application of somatic cell cloning to construct MSTN-edited Bama minipigs that carry only a single-base mutation and avoids biosafety risks to a large extent, thereby providing experience and a reference for the base editing of other genetic loci in Bama minipigs., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To compare the diagnostic performance of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and high-resolution ultrasound (HRUS) in euthyroid Hashimoto's thyroiditis (HT). Methods: From January 2016 to January 2019, patients with complete data of preoperative thyroid function, TPOAb, TgAb and HRUS who had undergone thyroid surgery treatment at the First Affiliated Hospital with Nanjing Medical University were reviewed. The diagnostic value of different diagnostic methods was compared using histopathology (HP) examination result as the gold standard. Results: The data of 792 patients (217 males and 575 females) was retrospectively collected. The M ( Q 1 , Q 3 )of patients' age was 41(32,52)years and the range was 16-75 years. With HP as the diagnostic gold standard, TPOAb exhibited similar sensitivity (59.3% vs 61.2%, P =0.752), accuracy (85.0% vs 83.6%, P =0.379), area under the receiver operating characteristic curve (AUC) (0.767 vs 0.764, P =0.886) and higher specificity (94.2% vs 91.6%, P =0.033) when compared with TgAb in diagnosing euthyroid HT. They both exhibited a higher sensitivity (59.3% vs 44.5%, P = 0.002; 61.2% vs 44.5%, P< 0.001), accuracy (85.0% vs 79.7%, P = 0.001; 83.6% vs 79.7%, P = 0.013) and AUC (0.767 vs 0.684, P< 0.001; 0.764 vs 0.684, P< 0.001) than HRUS. Compared with each method alone, the sensitivity and AUC of TPOAb combined with TgAb or HRUS were improved. The combination of three methods showed the greatest sensitivity. Concordance analysis demonstrated that TPOAb and HP had a moderate agreement (Kappa=0.580, 95% CI :0.513-0.647, P <0.001). Conclusions: The combination of thyroid antibodies, TPOAb and TgAb, can improve sensitivity, accuracy and AUC of diagnosis in euthyroid Hashimoto's thyroiditis. The two antibodies combined with HRUS exhibited the highest diagnostic performance. Elevated TPOAb showed moderate diagnostic consistency with histopathologic evidence of HT.