Search

Purpose: Head and neck squamous cell carcinomas (HNSCCs) are heterogeneous and complex malignancies. The present study aimed to explore potential molecular classifications and establish promising prognostic candidate biomarkers for human papillomavirus (HPV)‐negative HNSCC. Methods: We performed unsupervised clustering in HPV‐negative patients from the TCGA‐HNSCC database and identified molecular subclusters based on HNSCC prognosis. Weighted gene co‐expression network analysis was used to identify cluster‐related gene modules and identify reliable candidate genes. Biomarker signature was established from these candidate genes via 10‐fold cross validation in a least absolute shrinkage and selection operator (LASSO) Cox regression model and validated in The Cancer Genome Atlas Program (TCGA) cohort and four external Gene Expression Omnibus (GEO) validation cohorts. Results: We identified three molecular subclusters (C1–C3), and tumour microenvironment and survival evaluation results showed that C3 had high immune cell infiltration and better prognosis. However, C1 and C2 had low immune cell infiltration, and C1 had a worse survival outcome. A 20‐gene signature was established from the input candidate genes via 10‐fold cross validation in the LASSO Cox regression model. The signature was first validated in a training cohort, followed by a testing cohort and the entire cohort. A total of 347 patients from four external GEO validation cohorts indicated great performance of the signature in predicting outcomes. Conclusion: Compared with HPV‐positive patients, those with HPV‐negative HNSCC had an immunosuppressed tumour microenvironment. The 20‐gene signature was developed based on the characteristic unsupervised clustering molecular subclusters to predict survival outcomes in patients with HPV‐negative HNSCC. [ABSTRACT FROM AUTHOR]

In this paper, a joint detection strategy of Willie based on two phases observation is proposed and an energy‐efficient covert communication scheme with an adaptive assist nodes group (AANG) based on uniform jamming power (UJP) strategy is proposed to against the joint‐phase detection of Willie, which achieves covert communication with lower energy cost and higher average covert rate (ACR). The probability of detection error (PDE) at Willie with joint‐phase detection and ACR are derived. Furthermore, the optimal power allocation of legitimate transmitters is resolved to maximize ACR. Numerical results demonstrate the benefit of the proposed scheme over the covert rate and consumed jamming power. [ABSTRACT FROM AUTHOR]

Background: To explore the short‐ and long‐term outcomes in patients with nasopharyngeal carcinoma (NPC) with magnetic resonance imaging (MRI)‐detected residual disease at 3 months post‐treatment who received intervention either promptly (0 month) or following observation (after an additional 3 months). Methods: A total of 272 patients with residual disease at 3 months post‐treatment (observation [observation for additional 3 months]: 122, intervention [prompt intervention]: 150) were analyzed. Univariate and multivariate analyses were performed to examine the survival. Adverse events were analyzed in all patients. Results: Patients in the observation group had a lower 3‐year overall survival (77.1% vs. 85.2%), progression‐free survival (10.2% vs. 18.1%), and locoregional relapse‐free survival (10.2% vs. 20.6%) (all p <.05), but not distant metastasis‐free survival (83.8% vs. 78.4%, p =.189), whereas patients in the intervention group achieved higher complete remission (CR) rates (43.3% vs. 21.2%, p =.003). Patients who achieved CR after prompt intervention had a better survival rate than those who achieved observation‐CR or non‐CR (p <.001). Multivariate analyses revealed that a wait‐and‐see policy was an independent prognostic factor for impaired survival (p <.001). No significant differences of acute or late toxicities were observed between the two groups. Conclusions: Patients with NPC with MRI‐detected residual disease 3 months post‐radiotherapy should be encouraged to undergo prompt intervention rather than adopting a passive wait‐and‐see policy. [ABSTRACT FROM AUTHOR]

In light of the prelingual deafness and early-adulthood-onset dystonia in this case, combined with the family history and negative results of laboratory and imaging tests, the diagnosis of DDS was suspected. 9 Havránková P, Jech R, Roth J, Urgosík D, Ruzicka E. Beneficial effect of deep brain stimulation of GPi in a patient with dystonia-deafness phenotype. Keywords: dystonia; subthalamic nucleus; stimulation EN dystonia subthalamic nucleus stimulation 1124 1127 4 11/07/22 20221101 NES 221101 Dystonia-deafness syndrome (DDS) is a distinct clinical entity with an unclear pathophysiological mechanism. 8 Dulski J, Schinwelski M, Mandat T, Pienczk-Reclawowicz K, Slawek J. Long-term follow-up with video of a patient with deafness-dystonia syndrome treated with DBS-GPi. [Extracted from the article]

In order to counter the double attack with wardens and eavesdroppers in the practical scenario, a distributed transmission scheme with security and covertness is proposed, which combines coding techniques and transmission protocol. The covert message is encoded by rateless codes and transmitted embedded in normal frames. The security is based on the random essence of rateless coding, and the covertness is achieved by ignoring the error frames and maintaining the signal waveform. The inter‐collusion between multiple wardens and eavesdroppers greatly increases the potential security hazards, which is first discussed in this paper. The authors can counter the inter‐collusion attack by adjusting the ratio of covert frame transmission in the distributed transmission scheme with security and covertness. Compared with the related work, this paper has many advantages, such as good robustness, lower extra complexity, and the insurance of the performance for both normal message and covert message. The analysis and simulation results show that our distributed transmission scheme with security and covertness can achieve both covertness and security based on the effective design under the existing communication system. [ABSTRACT FROM AUTHOR]

This letter proposes a joint weighted power detector based on maximum a posteriori probability criterion for Willie aiming at two‐hop covert communication scenario, which is a near optimal detector. Instead of only supervising one single phase, Willie combines the observations of two phases to make joint decision in the proposed scheme. The proposed scheme achieves lower probability of detection error than adding‐power‐directly‐detector scheme and the existing single‐phase‐detector scheme due to sufficient utilization of the two‐phase observations. Numerical results demonstrate the benefit of authors' proposed scheme. [ABSTRACT FROM AUTHOR]

Summary: A gene upregulated in Nicotiana benthamiana after Bamboo mosaic virus (BaMV) infection was revealed as 1‐deoxy‐d‐xylulose‐5‐phosphate reductoisomerase (NbDXR). DXR is the key enzyme in the 2‐C‐methyl‐d‐erythritol‐4‐phosphate (MEP) pathway that catalyzes the conversion of 1‐deoxy‐d‐xylulose 5‐phosphate to 2‐C‐methyl‐d‐erythritol‐4‐phosphate.Knockdown and overexpression of NbDXR followed by BaMV inoculation revealed that NbDXR is involved in BaMV accumulation. Treating leaves with fosmidomycin, an inhibitor of DXR function, reduced BaMV accumulation. Subcellular localization confirmed that DXR is a chloroplast‐localized protein by confocal microscopy. Furthermore, knockdown of 1‐hydroxy‐2‐methyl‐2‐(E)‐butenyl‐4‐diphosphate reductase, one of the enzymes in the MEP pathway, also reduced BaMV accumulation. The accumulation of BaMV increased significantly in protoplasts treated with isopentenyl pyrophosphate. Thus, the metabolites of the MEP pathway could be involved in BaMV infection.To identify the critical components involved in BaMV accumulation, we knocked down the crucial enzyme of isoprenoid synthesis, NbGGPPS11 or NbGGPPS2. Only NbGGPPS2 was involved in BaMV infection. The geranylgeranyl pyrophosphate (GGPP) synthesized by NbGGPPS2 is known for gibberellin synthesis. We confirmed this result by supplying gibberellic acid exogenously on leaves, which increased BaMV accumulation.The de novo synthesis of gibberellic acid could assist BaMV accumulation. [ABSTRACT FROM AUTHOR]

Background: Lymph node (LN) metastasis is crucial in determining the prognosis and treatment options for colon cancer patients. Our work was to study whether the lymph nodes beyond D3 station in transverse colon cancer, especially 206 LN, should be dissected. Methods: A total of 225 patients within our department were reviewed. The primary and secondary endpoints were overall survival (OS) and disease‐free survival (DFS). We employed Propensity score weighting (PSW) for weighing participants to balance observed confounders between the 206D+ group and the 206D− group. Results: The rate of metastasis in station 206 was 9.3%. Only T stage (OR, 3.009; 95% CI, 1.018–8.892), N stage (OR, 9.818; 95% CI, 1.158–83.227), and M stage (OR, 26.126; 95% CI, 1.274–535.945) were an independent risk factor for 206 station metastasis in multivariate logistic analysis. The 206D+ group had a similarly survival than the 206D− group (3‐year DFS, 89.6% v 85.9%; p = 0.389; 3‐year OS, 94.6% v 85.3% p = 0.989). PSW further verified it. Metastasis of 206 station LN is not an independent prognostic factor, but a predictive factor of DFS. Conclusion: Station 206 LN positive is a predictive factor for DFS. Only the patient with T1‐3, N+ who is at a high risk of 206 station LN metastases should consider dissecting 206 station LN. [ABSTRACT FROM AUTHOR]

In this study, twenty‐six peanut varieties and their cold‐pressed oils from eleven provinces in China were investigated for their oil content, acid value, peroxide value, fatty acid profiles, bioactive constituents, and induction period (IP) of lipid oxidation. Meanwhile, the effect of the geographical origin of peanut on the quality of cold‐pressed peanut oils (CPOs) was studied. The average acid value of CPOs in southern China was higher than that in northern China (0.49 mg KOH/g versus 0.22 mg KOH/g, p >.05). In addition, the average of oleic acid content, ratio of oleic acid to linoleic acid (O/L), and IP were also higher in southern China than that in northern China (p <.05). However, the average content of campesterol, β‐sitosterol, total phytosterol, linoleic acid, and ratio of unsaturated fatty acid to saturated fatty acid (UFA/SFA) exhibited reverse results (p <.05). At last, the comprehensive evaluation of CPOs based on principal component analysis (PCA) was performed. In all samples, Silihong from Liaoning province, northern China was No.1, and Zhonghua 21 from Xiaogan City, Hubei Province was No.4 which was the first one from southern China. Moreover, heat map clustering analysis further revealed the differences and similarities among different samples, and those results were in accordance with the comprehensive evaluation results. [ABSTRACT FROM AUTHOR]

In shadow detection area, deep learning‐based methods have achieved outstanding performance. However, the potential ambiguity in shadow images is still the main reason for the poor performance of the algorithms. By analysing the relationships among shadow edges, shadow false‐positive information, and shadow areas, an edge‐guided disambiguation module for better shadow detection performance is proposed. The edge‐guided disambiguation module consists two parts: 1) the shadow edge feature is used to guide the comprehensive shadow area feature generation of different resolution. 2) The shadow false‐positive features is applied to reduce ambiguity in the comprehensive shadow area features. In this way, the missed detections is added in the first step and the false detections is reduced in the second step. More accurate detection results is obtained. The comprehensive experiments are proceeded on the three public shadow detection datasets: SBU, UCF, and ISTD. The experimental results demonstrated the effectiveness and robustness of the proposed method. [ABSTRACT FROM AUTHOR]

Aim: To explore the clinical factors associated with pathologic complete response (pCR) for locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and develop a web‐based dynamic nomogram. Methods: Retrospective analysis of patients with examination confirmed LARC from 2011 to 2022. Patients from the Union Hospital of Fujian Medical University were included as the training cohort (n = 1579) and Zhangzhou Hospital of Fujian Medical University as the external validation cohort (n = 246). Results: In the training cohort, after nCRT, 350 (22.2%) patients achieved pCR. More stomas were avoided in pCR patients (73.9% vs. 69.7%, p = 0.043). After a median follow‐up time of 47.7 months (IQR 2–145) shown OS (5‐year: 93.7% vs. 81.0%, HR = 0.310, 95%CI: 0.189–0.510, p < 0.001) and DFS (5‐year: 91.2% vs. 75.0%, HR = 0.204, 95%CI: 0.216–0.484, p < 0.001) were significantly better among patients with pCR than non‐pCR. Multivariable Logistic analysis shown pCR was significantly associated with Pre‐CRT CEA (HR = 0.944, 95%CI: 0.921–0.968; p < 0.001), histopathology (HR = 4.608, 95%CI: 2.625–8.089; p < 0.001), Pre‐CRT T stage (HR = 0.793, 95%CI: 0.634–0.993; p = 0.043), Pre‐CRT N stage (HR = 0.727, 95%CI: 0.606–0.873; p = 0.001), Pre‐CRT MRI EMVI (HR = 0.352, 95%CI: 0.262–0.473; p < 0.001), total neoadjuvant therapy (HR = 2.264, 95%CI: 1.280–4.004; p = 0.005). Meanwhile, the online version of the nomogram established in this study was publicized on an open‐access website (URL: https://pcrpredict.shinyapps.io/LARC2/). The model predicted accuracy with a C‐index of 0.73 (95% CI: 0.70–0.75), with an average C‐index of 0.73 for the internal cross validation and 0.78 (95% CI: 0.72–0.83) for the external validation cohort, showing excellent model accuracy. Delong test results showed the model has an important gain value for clinical characteristics to predict pCR in rectal cancer. Conclusions: Patients with pCR had a better prognosis, including OS and DFS, and were independently associated with Pre‐CRT CEA, histopathology, Pre‐CRT T/N stage, Pre‐CRT MRI EMVI, and TNT. A web‐based dynamic nomogram was successfully established for clinical use at any time. [ABSTRACT FROM AUTHOR]

In order to encourage innovative medicine to address Chinese unmet medical needs, China has changed its drug regulatory landscape to speed up access to new medicines. In order to understand the fast‐changing landscape and to enable planning of more global drug development programs and study designs in China, we reviewed 15 published clinical pharmacology‐related guidances by the National Medical Products Administration (NMPA), and compared them with reference guidances from the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), or the International Conference on Harmonization (ICH), to understand the similarities and differences, especially any China‐specific requirements, such as ethnic sensitivity analysis. Overall, by reviewing these clinical pharmacology‐related NMPA guidances, it is clear that NMPA guidances are very similar to FDA, EMA, and ICH guidances. There are no relevant differences in the major principles, but some differences in structure, contents, and focus were noted. The NMPA is adapting flexibility statements into newly published guidances. Ethnic sensitivity analysis needs to be implemented early in drug development plans. The NMPA encourages sponsors to conduct early clinical trials in China or include China early in multiregional clinical trials, and to obtain safety, efficacy, and pharmacokinetic data for ethnic sensitivity analysis. Depending on the stage of development, ethnic sensitivity analysis can be conducted using in vitro or literature data, other Asian clinical data, or Chinese clinical data. [ABSTRACT FROM AUTHOR]

Chinese English‐language journals in science, technology, and medicine have received scholarly attention, but little is known about their counterparts in the humanities and social sciences. A full understanding of the internationalization of Chinese English‐language humanities and social sciences journals (CELHSSJs) is not possible without an exploration of the phenomenon's social, political, and economic roots. Based on interviews with 26 stakeholders, including journal editors, heads of academic institutes, personnel from related regulatory state administrations, and international publishers, this article explores the implications of the development of CELHSSJs. Rather than treating the realms of academia and politics as distinct, opposing factors, we examine the complicated situation in China. English‐language journals carry out the political mission of the government's 'going out' propaganda policy. For academics and universities, they are largely a means for competing for resources domestically and a venue for power negotiations with overseas publishing groups. Based on our investigation of the dynamics and contradictions involved in the development of CELHSSJs, we argue that the power dynamics and social contexts in which Chinese English‐language journals operate shape China's knowledge production and dissemination as much as the content of these journals does. [ABSTRACT FROM AUTHOR]

With the rapid development of voltage source converter based high-voltage direct current, power flow analysis becomes increasingly important for AC/DC hybrid systems. This study extends the holomorphic embedding (HE) method to the VSC-based AC/DC power flow problem. With an appropriate embedding technique, a general embedded model is established for AC/DC power flow with VSCs, which can not only preserve the deterministic property of HE that enables it to derive the desired solution in an explicit manner but also flexibly accommodate various bus types, VSC configurations, control strategies and operating conditions. Moreover, the sparsity of the recursive matrix in power series calculations and the introduction of the iterative calculation of the inverse matrix (ICIM) to rational approximants contribute to the high computational efficiency of the model. The proposed method is shown to be feasible and efficient by illustrative cases and is further extended to multi-terminal (VSC-MTDC) configurations to verify its flexibility. [ABSTRACT FROM AUTHOR]

With the rapid development of voltage source converter based high‐voltage direct current, power flow analysis becomes increasingly important for AC/DC hybrid systems. This study extends the holomorphic embedding (HE) method to the VSC‐based AC/DC power flow problem. With an appropriate embedding technique, a general embedded model is established for AC/DC power flow with VSCs, which can not only preserve the deterministic property of HE that enables it to derive the desired solution in an explicit manner but also flexibly accommodate various bus types, VSC configurations, control strategies and operating conditions. Moreover, the sparsity of the recursive matrix in power series calculations and the introduction of the iterative calculation of the inverse matrix (ICIM) to rational approximants contribute to the high computational efficiency of the model. The proposed method is shown to be feasible and efficient by illustrative cases and is further extended to multi‐terminal (VSC‐MTDC) configurations to verify its flexibility. [ABSTRACT FROM AUTHOR]

Tomato spotted wilt virus (TSWV) is one of the most devastating plant viruses and often causes severe crop losses worldwide. Generally, mature plants become more resistant to pathogens, known as adult plant resistance. In this study, we demonstrated a new phenomenon involving developmentally regulated susceptibility of Arabidopsis thaliana to TSWV. We found that Arabidopsis plants become more susceptible to TSWV as plants mature. Most young 3‐week‐old Arabidopsis were not infected by TSWV. Infection of TSWV in 4‐, 5‐, and 6‐week‐old Arabidopsis increased from 9%, 21%, and 25%, respectively, to 100% in 7‐ to 8‐week‐old Arabidopsis plants. Different isolates of TSWV and different tospoviruses show a low rate of infection in young Arabidopsis but a high rate in mature plants. When Arabidopsis dcl2/3/4 or rdr1/2/6 mutant plants were inoculated with TSWV, similar results as observed for the wild‐type Arabidopsis plants were obtained. A cell‐to‐cell movement assay showed that the intercellular movement efficiency of TSWV NSm:GFP fusion was significantly higher in 8‐week‐old Arabidopsis leaves compared with 4‐week‐old Arabidopsis leaves. Moreover, the expression levels of pectin methylesterase and β‐1,3‐glucanase, which play critical roles in macromolecule cell‐to‐cell trafficking, were significantly up‐regulated in 8‐week‐old Arabidopsis leaves compared with 4‐week‐old Arabidopsis leaves during TSWV infection. To date, this mature plant susceptibility to pathogen infections has rarely been investigated. Thus, the findings presented here should advance our knowledge on the developmentally regulated mature host susceptibility to plant virus infection. [ABSTRACT FROM AUTHOR]

Summary: RNA silencing is a major defense mechanism against invading viruses in plants. Argonaute proteins (AGOs) are the key players in RNA silencing. The number of AGO family members involved varies depending on the plant species and they play distinct or sometimes redundant roles in antiviral defense.By using a virus‐induced gene silencing technique, it was found that Nicotiana benthamiana AGO1 restricted Bamboo mosaic virus (BaMV) accumulation, but NbAGO10, the closest paralog of NbAGO1, positively regulated BaMV accumulation.Immunoprecipitation assay revealed BaMV virus‐derived small interfering RNAs (vsiRNAs) in NbAGO10 complexes. Transient overexpression of NbAGO10 increased BaMV RNA accumulation, but with co‐expression of NbAGO1, BaMV RNA accumulation was reduced, which suggests that NbAGO10 may have competed with NbAGO1 for sequestering BaMV vsiRNA and prevented the formation of RNA‐induced silencing complexes. In addition, overexpression of NbAGO10 decreased BaMV vsiRNA accumulation. A host enzyme, small RNA degrading nuclease 1 (SDN1), also was found to interact with NbAGO10 on in vivo pull‐down assay. Silencing of SDN1 elevated BaMV vsiRNA level and decreased BaMV RNA accumulation in N. benthamiana, indicating that NbAGO10 might recruit SDN1 for BaMV vsiRNA degradation.The results herein suggested that NbAGO10 plays a pro‐viral role by BaMV vsiRNA sequestration and degradation. [ABSTRACT FROM AUTHOR]

Theta‐burst stimulation (TBS) is a varied form of repetitive transcranial magnetic stimulation (rTMS) and has more rapid and powerful effects than rTMS. Experiments on the human motor cortex have demonstrated that intermittent TBS has facilitatory effects, whereas continuous TBS has inhibitory effects. Huang's simplified model provides a solid basis for elucidating such after‐effects. However, evidence increasingly indicates that not all after‐effects of TBS are as expected, and high variability among individuals has been observed. Studies have suggested that the GABAergic and glutamatergic neurotransmission play a vital role in the aforementioned after‐effects, which might explain the interindividual differences in these after‐effects. Herein, we reviewed the latest findings on TBS from animal and human experiments on glutamatergic and GABAergic neurotransmissions in response to TBS. Furthermore, an updated theoretical model integrating glutamatergic and GABAergic neurotransmissions is proposed. [ABSTRACT FROM AUTHOR]

Key Points: Synaptic plasticity is involved in daily activities but abnormal plasticity may be deleterious. In this study, we found that motor plasticity could be modulated by suppressing the premotor cortex with the theta burst form of repetitive transcranial magnetic stimulation. Such changes in motor plasticity were associated with reduced learning of a simple motor task. We postulate that the premotor cortex adjusts the amount of motor plasticity to modulate motor learning through heterosynaptic metaplasticity. The present results provide an insight into how the brain physiologically coordinates two different areas to bring them into a functional network, a concept that could be employed to intervene in diseases with abnormal plasticity. Abstract: Primary motor cortex (M1) plasticity is known to be influenced by the excitability and prior activation history of M1 itself. However, little is known about how its plasticity is influenced by other areas of the brain. In the present study on humans of either sex who were known to respond to theta burst stimulation from previous studies, we found plasticity of M1 could be modulated by suppressing the premotor cortex with the theta burst form of repetitive transcranial magnetic stimulation. Motor plasticity was distorted and disappeared 30 min and 120 min, respectively, after premotor excitability was suppressed. Further evaluation revealed that such changes in motor plasticity were associated with impaired learning of a simple motor task. We postulate that the premotor cortex modulates the amount of plasticity within M1 through heterosynaptic metaplasticity, and that this may impact on learning of a simple motor task previously shown to be directly affected by M1 plasticity. The present results provide an insight into how the brain physiologically coordinates two different areas to bring them into a functional network. Furthermore, such concepts could be translated into therapeutic approaches for diseases with aberrant plasticity. [ABSTRACT FROM AUTHOR]

Abstract: The number of elderly patients with cancer is increasing. Medical comorbidities are more common in this population. Little is known regarding the prognostic relevance of comorbidities in elderly patients with nasopharyngeal carcinoma (NPC). Using the National Cancer Data Base (NCDB), we queried patients age >65 years diagnosed with NPC and treated with definitive radiation between 2004 and 2012 to examine the association between comorbidity and survival outcomes. Comorbidity was assessed with the Charlson Comorbidity Index (CCI). The influence of comorbidity on overall survival (OS) was evaluated. Cox proportional hazards model was used to study the impact of comorbidity on OS. A total of 1137 patients met the specified criteria. Median follow‐up was 61.2 months. Five‐year OS was 50.4%. Comorbidities were present in 22.4% of patients, with 17.6% of patients having a CCI score of 1% and 4.8% having a CCI score of ≥2. Patients with a CCI score of 0 had significantly higher 5‐year OS than patients with a CCI score of 1 or ≥2 (53.1% vs. 42.2% vs. 32.9%, P < 0.001). In multivariate analysis, CCI was a statistically significant independent prognostic factor for the risk of death of all causes for patients with a CCI score of 1 (hazard ratio [HR]: 1.242; 95% confidence interval [CI]: 1.002–1.539) or CCI score of ≥2 (HR: 1.625; 95% CI: 1.157–2.283) when compared to patients with a CCI score of 0. Comorbidity as measured by CCI is a strong independent prognostic factor for OS in elderly patients with NPC and lends support to the inclusion of comorbidity assessment due to its prognostic value when treating elderly patients with NPC. [ABSTRACT FROM AUTHOR]

Background Environmental enrichment ( EE) has been shown to enhance cognitive function in mouse models of Alzheimer's disease ( AD). Magnesium-L-threonate (MgT) is a compound with a newly discovered effect to rescue learning and memory function in aging and AD mice. Aim To study the additive therapeutic effect of EE combined with MgT ( EM) and the potential mechanism underlying the effects. Materials and Methods APP/ PS1 mice were treated with EE, MgT, or combination of EE and MgT ( EM) and compared for restored memory function. Results EM was more effective in improving cognition and spatial memory than either treatment alone in either long-term (12 months, started at 3 months old, which was before disease manifestation) or short-term (3 months, started at 6 months old, which was after disease manifestation) treatment. The behavioral improvement has coincided with rescue of synaptic contacts in the hippocampal region of the AD mouse brain. Immunoblots also showed that EM but neither single treatment rescued the activity reduction in Ca MKII and CREB, two important downstream molecules in the N-methyl-D-aspartate receptor ( NMDAR) pathway. Conclusion Environmental enrichment and MgT may synergistically improve recognition and spatial memory by reducing synaptic loss and restoring the NMDAR signaling pathway in AD mice, which suggests that combination of EE and MgT may be a novel therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the incidence, consequences, and predictors of serious chemotherapy‐induced thrombocytopenia (CIT) in nasopharyngeal carcinoma (NPC). Materials and Methods: We retrospectively reviewed the clinical records of patients with NPC between 2013 and 2015. Multivariate Cox proportional hazards regression model and propensity score matching were used to estimate the effect of serious CIT on overall survival. Univariate and multivariate logistic regression analyses were applied to identify the predictors of serious CIT. Results and Conclusion: The incidence of serious CIT was 5.21% in patients with NPC. Patients who experienced serious thrombocytopenia had a worse long‐term prognosis, while the difference in short‐term survival rate was slight. Chemotherapy regimens of gemcitabine and platinum, 5‐fluorouracil and platinum, taxane and platinum, serum potassium ion concentration, serum lactate dehydrogenase levels, platelet count, red blood cell count, and estimated glomerular filtration rate were predictors of serious CIT. [ABSTRACT FROM AUTHOR]

The screening of differentially expressed genes in plants after pathogen infection can uncover the potential host factors required for the pathogens. In this study, an up-regulated gene was identified and cloned from N icotiana benthamiana plants after B amboo mosaic virus ( BaMV) inoculation. The up-regulated gene was identified as a member of the Rab small guanosine triphosphatase ( GTPase) family, and was designated as NbRABG 3f according to its in silico translated product with high identity to that of RABG 3f of tomato. Knocking down the expression of NbRABG 3f using a virus-induced gene silencing technique in a protoplast inoculation assay significantly reduced the accumulation of BaMV. A transiently expressed NbRABG3f protein in N . benthamiana plants followed by BaMV inoculation enhanced the accumulation of BaMV to approximately 150%. Mutants that had the catalytic site mutation ( NbRABG3f/ T22 N) or had lost their membrane-targeting capability ( NbRABG3f/Δ C3) failed to facilitate the accumulation of BaMV in plants. Because the Rab GTPase is responsible for vesicle trafficking between organelles, a mutant with a fixed guanosine diphosphate form was used to identify the donor compartment. The use of green fluorescent protein ( GFP) fusion revealed that GFP- NbRABG3f/ T22 N clearly co-localized with the Golgi marker. In conclusion, BaMV may use NbRABG3f to form vesicles derived from the Golgi membrane for intracellular trafficking to deliver unidentified factors to its replication site; thus, both GTPase activity and membrane-targeting ability are crucial for BaMV accumulation at the cell level. [ABSTRACT FROM AUTHOR]

Gliomas are common and refractory primary tumors closely associated with the fine structures of the brain. Photothermal therapy (PTT) has recently shown promise as an effective treatment for gliomas. However, nonspecific accumulation of photothermal agents may affect adjacent normal brain structures, and the inflammatory response induced during PTT may result in an increased risk of brain tumor recurrence or metastasis. Here, the design and fabrication of an intelligent nanomachine is reported based on Gd2O3@Ir/TMB‐RVG29 (G@IT‐R) hybrid nanomaterials. These nanomaterials enable tumor‐specific PTT and eliminate inflammation to protect normal brain tissue. The mechanism involves the rabies virus glycopeptide‐29 peptide (RVG29) passing through the blood–brain barrier (BBB) and targeting gliomas. In the tumor microenvironment, Ir nanozymes can act as logic control systems to trigger chromogenic reaction amplification of 3,3′,5,5′‐tetramethylbenzidine (TMB) for tumor‐specific PTT, whereas in normal brain tissues, they scavenge reactive oxygen species (ROS) generated by poor therapy and function as protective agents. Autophagy inhibition of Gd2O3 enables excellent photothermal therapeutic effects on orthotopic gliomas and protection against inflammation in normal cells. The results of this study may prove useful in developing highly efficient nanomedicines for glioma treatment. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The management of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) remains controversial. This study aimed to evaluate a novel IPFP preservation technique—“the medially pedicled IPFP flap”—for reducing postoperative pain, wound complications, and improving functional recovery after TKA.A retrospective analysis was conducted on TKA cases at our institution from 2018 to 2021, including those with IPFP preservation (medially pedicled flap) versus IPFP complete resection. Patient demographics, perioperative parameters (blood loss, operative time, length of hospital stay, visual analogue scale [VAS] score, white cell count [WBC], C‐reactive protein [CRP], erythrocyte sedimentation rate [ESR], and wound oozing), and postoperative follow‐up data (VAS, Knee Society [KSS], or Knee Society functional assessment [KSFA] scores) were compared between groups. Independent sample t‐tests were used to compare continuous data and chi‐squared tests were used to compare categorical data between groups.Six hundred thirty patients were included, with 278 in the medial pedicled IPFP flap group (preservation group) and 352 in the IPFP resection group (resection group). The operative time was significantly shorter in the preservation versus resection group (125.5 ± 23.2 vs 130.3 ± 28.7 mins, p = 0.03), as was the length of hospital stay (8.4 ± 2.7 vs 9.2 ± 2.3 days, p < 0.01). Regarding pain, the preservation group had significantly lower VAS scores on postoperative day 2 (2.0 ± 0.8 vs 2.4 ± 1.2, p < 0.001) and day 3 (1.5 ± 0.5 vs 1.8 ± 1.0, p < 0.001). CRP and ESR levels on postoperative day 5 were also significantly lower in the preservation group. Wound oozing rates were significantly lower in the preservation versus resection group (0.7% vs 2.8%, p = 0.04). No significant differences existed in VAS, KSS, or KSFA scores at the last follow‐up.The novel IPFP preservation technique significantly improved surgical exposure, shortened operative time and length of hospital stay. It also reduced wound pain and oozing compared to IPFP resection. [ABSTRACT FROM AUTHOR]

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self‐renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re‐epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non‐human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment. [ABSTRACT FROM AUTHOR]

Objectives: Primary pulmonary lymphoepithelioma‐like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein–Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB‐treated PLELC. Viral EBNA‐1 and BamHI‐W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results: Progression‐free survival (PFS) was significantly longer in EBNA‐1 high or BamHI‐W high groups. A longer PFS was also observed in patients with both high plasma EBNA‐1 or BamHI‐W and PD‐L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA‐1 and BamHI‐W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions: Plasma EBV DNA could be a useful and easy‐to‐use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging. [ABSTRACT FROM AUTHOR]

Accumulation of abnormal chondroitin sulfate (CS) chains in breast cancer tissue is correlated with poor prognosis. However, the biological functions of these CS chains in cancer progression remain largely unknown, impeding the development of targeted treatment focused on CS. Previous studies identified chondroitin polymerizing factor (CHPF; also known as chondroitin sulfate synthase 2) is the critical enzyme regulating CS accumulation in breast cancer tissue. We then assessed the association between CHPF‐associated proteoglycans (PGs) and signaling pathways in breast cancer datasets. The regulation between CHPF and syndecan 1 (SDC1) was examined at both the protein and RNA levels. Confocal microscopy and image flow cytometry were employed to quantify macropinocytosis. The effects of the 6‐O‐sulfated CS‐binding peptide (C6S‐p) on blocking CS functions were tested in vitro and in vivo. Results indicated that the expression of CHPF and SDC1 was tightly associated within primary breast cancer tissue, and high expression of both genes exacerbated patient prognosis. Transforming growth factor beta (TGF‐β) signaling was implicated in the regulation of CHPF and SDC1 in breast cancer cells. CHPF supported CS–SDC1 stabilization on the cell surface, modulating macropinocytotic activity in breast cancer cells under nutrient‐deprived conditions. Furthermore, C6S‐p demonstrated the ability to bind CS‐SDC1, increase SDC1 degradation, suppress macropinocytosis of breast cancer cells, and inhibit tumor growth in vivo. Although other PGs may also be involved in CHPF‐regulated breast cancer malignancy, this study provides the first evidence that a CS synthase participates in the regulation of macropinocytosis in cancer cells by supporting SDC1 expression on cancer cells. [ABSTRACT FROM AUTHOR]

Background: Thermage is a monopolar radiofrequency (RF). It has become an indispensable part of facial and body youthful methods. Although the current device is constantly improving in epidermal cooling techniques and even automatically measures the local impedance value, applying surface anesthesia can take some of the pain away caused by thermage, and the patient's severe pain in the jaw and neck areas is still difficult to resolve. Methods: The author describes how he uses the combination of the buccal nerve block (BNB) and the superficial cervical plexus block (SCPB) to improve the comfort of the patient's face and neck treatment of patients. It can improve the quality, elasticity, and texture of the skin. Results: According to the author's knowledge of oral and maxillofacial surgery, the combination of BNB and SCPB is applied to the neck and facial analgesia. Combining the BNB and SCPB effectively provides facial and neck anesthesia. The BNB in this technique provides pain relief to the facial skin in the mandibular area and SCPB offers pain relief to the skin of the neck. RF facial rejuvenation treatment often involves the junction of the face and neck to improve the contour of the mandibular margin. Therefore, Whether the RF treatment is aimed at the face or neck, or the treatment is performed simultaneously, we advocate the block both of the buccal nerve and the superficial cervical plexus nerves to achieve perfect analgesia. Still, the dosage of anesthetic medication for the nerve block can be adjusted according to the treatment area. Conclusion: We applied these two nerve blocks and their combination to improve skin laxity with RF therapy for the first time. [ABSTRACT FROM AUTHOR]

Aims: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. Methods: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety‐ and depression‐like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. Results: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety‐like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety‐like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N‐methyl‐D‐aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety‐like behaviors. Conclusions: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS‐like symptoms. These findings may give insight into the treatment of IBS and related psychological distress. [ABSTRACT FROM AUTHOR]

Substrate topographical features induce osteogenic differentiation of bone marrow stem cells (BMSCs), but the underlying mechanisms are unclear. As microRNAs (miRNAs) play key roles in osteogenesis and bone regeneration, it would be meaningful to elucidate the roles of miRNAs in the intracellular signaling cascade of topographical cue‐induced osteogenic differentiation. In this study, the miRNA expression profile of the topographical feature‐induced osteogenic differentiation group is different from that of the chemical‐factors‐induced osteogenic differentiation group. miR‐193a‐3p is sensitive to substrate topographical features and its downregulation enhances osteogenic differentiation only in the absence of osteogenesis−inducing medium. Also, substrate topographical features specifically activate a nonclassical osteogenetic pathway—the mitogen‐activated protein kinase (MAPK) pathway. Loss‐ and gain‐of‐function experiments demonstrate that miR‐193a‐3p regulates the MAPK pathway by targeting the MAP3k3 gene. In conclusion, this data indicates that different osteogenic‐lineage‐related intracellular signaling cascades are triggered in BMSCs subjected to biophysical or chemical stimulation. Moreover, the miR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic lineage specification of BMSCs, and hence may be a promising molecular target for bone regenerative therapies. [ABSTRACT FROM AUTHOR]

The orchid industry faces severe threats from diseases caused by viruses. Argonaute proteins (AGOs) have been shown to be the major components in the antiviral defence systems through RNA silencing in many model plants. However, the roles of AGOs in orchids against viral infections have not been analysed comprehensively. In this study, Phalaenopsis aphrodite subsp. formosana was chosen as the representative to analyse the AGOs (PaAGOs) involved in the defence against two major viruses of orchids, Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV). A total of 11 PaAGOs were identified from the expression profile analyses of these PaAGOs in P. aphrodite subsp. formosana singly or doubly infected with CymMV and/or ORSV. PaAGO5b was found to be the only one highly induced. Results from overexpression of individual PaAGO5 family genes revealed that PaAGO5a and PaAGO5b play central roles in the antiviral defence mechanisms of P. aphrodite subsp. formosana. Furthermore, a virus‐induced gene silencing vector based on Foxtail mosaic virus was developed to corroborate the function of PaAGO5s. The results confirmed their importance in the defences against CymMV and ORSV. Our findings may provide useful information for the breeding of traits for resistance or tolerance to CymMV or ORSV infections in Phalaenopsis orchids. [ABSTRACT FROM AUTHOR]

Emerging evidence suggested that epigenetic regulators can exhibit both activator and repressor activities in gene transcriptional regulation and disease development, such as cancer. However, how these dual activities are regulated and coordinated in specific cellular contexts remains elusive. Here, it is reported that KDM5C, a repressive histone demethylase, unexpectedly activates estrogen receptor alpha (ERα)‐target genes, and meanwhile suppresses type I interferons (IFNs) and IFN‐stimulated genes (ISGs) to promote ERα‐positive breast cancer cell growth and tumorigenesis. KDM5C‐interacting protein, ZMYND8, is found to be involved in both processes. Mechanistically, KDM5C binds to active enhancers and recruits the P‐TEFb complex to activate ERα‐target genes, while inhibits TBK1 phosphorylation in the cytosol to repress type I IFNs and ISGs. Pharmacological inhibition of both ERα and KDM5C is effective in inhibiting cell growth and tumorigenesis. Taken together, it is revealed that the dual activator and repressor nature of an epigenetic regulator together contributes to cancer development. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot ulcer (DFU) is a common and serious complication of diabetes, and its treatment is challenging. Platelet‐rich plasma (PRP) gel and umbilical cord mesenchymal stem cells (UC‐MSCs) gel have been concerned as new therapies for DFU in recent years, and comparative studies on the efficacy and mechanisms of these methods, however, are rarely reported. Methods: Thirty patients with DFU were selected and divided into the PRP group and the UC‐MSCs group, and wound healing, foot blood vessels (ABI index), infection index (CRP), neuropathy symptoms (TCSS score), and foot skin temperature before and after treatment were compared between the two groups. SPSS 21.0 was used for statistical analysis. Results: The results showed that the efficacy of the UC‐MSCs gel group was significantly better than that of the PRP group in terms of wound healing rate, time to complete wound closure, ABI index, CRP level and TCSS score. No statistically significant difference in foot skin temperature was observed between the two groups. Conclusion: The efficacy of UC‐MSCs gel is significantly superior to that of PRP gel in the treatment of DFU, with shortened time to complete wound closure, increased wound healing rate, better pain and infection control, and improved vascular and neurological symptoms. [ABSTRACT FROM AUTHOR]

Extranodal natural killer/T‐cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein–Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single‐cell RNA sequencing (scRNA‐seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single‐cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV‐encoded genes and low infiltration of tumor‐associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single‐cell resolution, highlighting the crucial role of malignant NK cells with EBV‐encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL. [ABSTRACT FROM AUTHOR]

The long noncoding RNA (lncRNA) AUXIN‐REGULATED PROMOTER LOOP (APOLO) recognizes a subset of target loci across the Arabidopsis thaliana genome by forming RNA–DNA hybrids (R‐loops) and modulating local three‐dimensional chromatin conformation. Here, we show that APOLO regulates shade avoidance syndrome by dynamically modulating expression of key factors. In response to far‐red (FR) light, expression of APOLO anti‐correlates with that of its target BRANCHED1 (BRC1), a master regulator of shoot branching in Arabidopsis thaliana. APOLO deregulation results in BRC1 transcriptional repression and an increase in the number of branches. Accumulation of APOLO transcription fine‐tunes the formation of a repressive chromatin loop encompassing the BRC1 promoter, which normally occurs only in leaves and in a late response to far‐red light treatment in axillary buds. In addition, our data reveal that APOLO participates in leaf hyponasty, in agreement with its previously reported role in the control of auxin homeostasis through direct modulation of auxin synthesis gene YUCCA2, and auxin efflux genes PID and WAG2. We show that direct application of APOLO RNA to leaves results in a rapid increase in auxin signaling that is associated with changes in the plant response to far‐red light. Collectively, our data support the view that lncRNAs coordinate shade avoidance syndrome in A. thaliana, and reveal their potential as exogenous bioactive molecules. Deploying exogenous RNAs that modulate plant–environment interactions may therefore become a new tool for sustainable agriculture. Synopsis: The Arabidopsis lncRNA APOLO influences chromatin architecture to regulate transcription of specific genes, including auxin‐responsive genes which are involved in the plant's response to shade avoidance. Here, APOLO is shown to respond to changes in light by influencing transcription and plant behavior. APOLO modulates the expression of BRANCHED1 (BRC1), a master regulator of shoot branching in Arabidopsis, through chromatin looping around the BRC1 promoter.APOLO‐mediated chromatin looping is influenced by changes in light exposure and regulates branching behavior.Low‐red/far‐red light ratio‐mediated leaf hyponasty depends on APOLO regulation of auxin‐related genes.In vitro‐transcribed APOLO directly sprayed onto plants is sufficient to alter plant auxin homeostasis in response to light conditions. [ABSTRACT FROM AUTHOR]

Benzoic acid (BA) is widely used as an antimicrobial preservative to prolong the shelf‐life of pickled vegetables. A method for rapidly determining the BA content in forty pickled vegetable samples was developed by coupling ultrasonic extraction with surface‐enhanced Raman scattering (SERS) and an adaptive iteratively reweighted penalized least‐squares (AirPLS) algorithm. The results obtained with this method were compared and correlated with those from high‐performance liquid chromatography measurements. Amplification of the Raman scattering via the SERS effect was induced by gold nanoparticles (AuNPs) when BA was irradiated with a 785 nm laser. The AirPLS algorithm was used to reduce the background interference signal, which was also amplified. The amplified Raman scattering effect of BA in the pickled vegetables displayed a positive and significant correlation with the HPLC concentration of BA, with high reproducibility. For HPLC determination of the concentration of BA in the range of 0–820 ppm, the BA monomer's intensity of the 944–1,005 cm−1 and 1,366–1,373 cm−1 peaks, and BA dimer's intensity of the 1,025 cm−1 and 1,465–1,482 cm−1 peaks in the SERS spectrum were respectively converted to the Z‐ratio BA monomer and Z‐ratio BA dimer standard scores by Z‐Score conversion. The sum's (Z‐ratio BA monomer + Z‐ratio BA dimer) sensitivity was 100%, and specificity was 90.9% by receiver operating characteristic curve. This study found that a Raman spectroscopy‐based monitoring method can be one of the fastest screening inspection options that can complete an analysis within a short period of time and produce reliable results. This approach is particularly cost‐effective, which makes it suitable for the initial screening of raw materials and provides an effective management strategy easy to communicate with food safety officials. [ABSTRACT FROM AUTHOR]

Limbal stem/progenitor cells (LSC) represent the source of corneal epithelium renewal. LSC proliferation and differentiation are essential for corneal homeostasis, however, the regulatory mechanism remains largely unexplored. Here, we performed single‐cell RNA sequencing and discovered proliferation heterogeneity as well as spontaneously differentiated and senescent cell subgroups in multiply passaged primary LSC. Fasciculation and elongation protein zeta 1 (FEZ1) and Dickkopf‐1 (DKK1) were identified as two significant regulators of LSC proliferation and senescence. These two factors were mainly expressed in undifferentiated corneal epithelial cells (CECs). Knocking down the expression of either FEZ1 or DKK1 reduced cell division and caused cell cycle arrest. We observed that DKK1 acted as a downstream target of FEZ1 in LSC and that exogenous DKK1 protein partially prevented growth arrest and senescence upon FEZ1 suppression in vitro. In a mouse model of corneal injury, DKK1 also rescued the corneal epithelium after recovery was inhibited by FEZ1 suppression. Hence, the FEZ1–DKK1 axis was required for CEC proliferation and the juvenile state and can potentially be targeted as a therapeutic strategy for promoting recovery after corneal injury. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to compare the use of qualitative fetal fibronectin, quantitative fetal fibronectin, and placental α-microglobulin-1 in women with symptoms of preterm labor, to evaluate which vaginal biomarker performs the best in clinical practice.Material and Methods: This prospective observational study included women who presented with symptoms of preterm labor at 24+0 to 34+0  weeks of gestation at a large tertiary maternity hospital in Auckland, New Zealand. Women were managed according to hospital guidelines using qualitative fetal fibronectin. Quantitative fetal fibronectin and placental α-microglobulin-1 tests were also taken, with clinicians blinded to the results. Management and delivery outcomes were collected from clinical records. The primary outcome was the rate of antenatal hospital admission. Analysis was performed according to predefined management protocols for each of the tests.Results: A total of 128 women had all three biomarkers tests taken. Spontaneous preterm birth rates were 7/128 (5.5%) ≤34+0  weeks and 20/128 (15.6%) <37+0  weeks of gestation; 5/128 (3.9%) delivered within 7 days of testing. Positive results were recorded in 28 qualitative fetal fibronectin tests, 25 quantitative fetal fibronectin tests with 11 ≥200 ng/mL, and 16 placental α-microglobulin-1 tests. The use of quantitative fetal fibronectin or placental α-microglobulin-1 would have lowered antenatal admission rates: 27/128 (21.1%) for qualitative fetal fibronectin, 11/128 (8.6%) for quantitative fetal fibronectin (admission threshold ≥200 ng/mL), and 15/128 (11.7%) for placental α-microglobulin-1. No additional women with quantitative fetal fibronectin <200 ng/mL delivered within 7 days or missed corticosteroids compared with standard care (qualitative fetal fibronectin); however, an additional 3 cases had a false-negative placental α-microglobulin-1 and clinical care may have been compromised (no antenatal corticosteroids or admission).Conclusions: The use of quantitative fetal fibronectin (admission threshold ≥200 ng/mL) has the potential to reduce the rate of antenatal admissions for women with symptoms of preterm labor without compromising use of antenatal interventions that improve outcomes for babies born preterm. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the risk stratification among elderly Nasopharyngeal carcinoma (NPC) patients (≥60 years old) and select the beneficiaries from concurrent chemotherapy (CCRT) combined with induction chemotherapy (IC). Materials and Methods: A total of 909 elderly non‐metastatic NPC patients treated with cisplatin‐based CCRT or IC + CCRT between January 2007 and December 2016 were included. Prognostic nomograms were generated according to clinical characteristics and serum biomarkers. The survival outcomes of patients treated with CCRT versus IC + CCRT were compared in three well‐matched risk groups (high, medium, and low risk) after PSM analysis. Benefit of IC in people older or younger than 70 years and effect of different IC regimens and cycles on prognosis were analyzed. Results: Nomograms of overall survival (OS) (C‐index: 0.64, 95% CI, 0.61–0.89) and disease special survival (DSS) (C‐index: 0.65, 95% CI, 0.62–0.71) showed good prognostic accuracy. The nomogram for DSS included variables of age, gender, ACE, EBV DNA, N stage, and T stage. OS included variables of age, smoking history, ACE, ALB, EBV DNA, N stage, and T stage. The corresponding 5‐year OS rates of high, medium and low risk groups were 87.4%, 82.2%, and 60.9%, respectively (p < 0.001), while the 5‐year DSS rates were 92.2%, 84.3%, and 69.0%, respectively (p < 0.001). In the high risk group, IC + CCRT led to significantly higher 5‐year OS and DSS rate compared with CCRT (5‐year OS rate, 73.5% versus 51.8%, p = 0.006; 5‐year DSS rate, 81.4% versus 61.3%, p = 0.002). While in the medium and low risk groups, OS and DSS were not significantly different (OS: p = 0.259, 0.186; DSS: p = 0.29, 0.094). Subgroup analysis showed in the high risk group, only people younger than 70 years old could benefit from IC. TPF and IC cycles of three could lead to the best survival results. Conclusion: Compared with CCRT, OS, and DSS among high risk elderly patients were significantly improved by the addition of IC in patients younger than 70 years old. TPF and three IC cycles were recommended. [ABSTRACT FROM AUTHOR]

Background: Relapsed or refractory Hodgkin lymphoma (R/R HL) is a challenging disease with limited treatment options beyond brentuximab vedotin and checkpoint inhibitors. Herein we present the time‐trend analysis of R/R HL patients who received allogeneic hematopoietic cell transplantation (allo‐HCT) at our center from 2001–2017. Methods: The patients were divided into two distinct treatment cohorts: era1 (2001–2010), and era2 (2011–2017). The primary endpoint was overall survival (OS). Secondary endpoints included progression‐free survival (PFS), non‐relapse mortality (NRM), and cumulative incidence of acute and chronic graft versus host disease (GVHD). Results: Among the 51 patients included in the study, 29 were in era1, and 22 were in era2. There was decreased use of myeloablative conditioning in era2 (18% vs. 31%) compared to era1 and 95% of patients in era2 previously received brentuximab Vedotin (BV). Haploidentical donors were seen exclusively in era2 (0% vs. 14%) and more patients received alternative donor transplants (7% vs. 32%) in era2. The 4‐year OS (34% vs. 83%, p < 0.001) and 4‐year PFS (28% vs. 62%, p = 0.001) were significantly inferior in era1 compared to era2. The incidence of 1‐year NRM was lower in era2 compared to era1 (5% vs. 34%, p = 0.06). The cumulative incidence of acute GVHD at day 100 was similar in both eras (p = 0.50), but the incidence of chronic GVHD at 1 year was higher in era2 compared to era1 (55% vs. 21%, p = 0.03). Conclusions: Despite the advent of novel therapies, allo‐HCT remains an important therapeutic option for patients with R/R HL. [ABSTRACT FROM AUTHOR]

Summary: An up‐regulated gene derived from Bamboo mosaic virus (BaMV)‐infected Nicotiana benthamiana plants was cloned and characterized in this study. BaMV is a single‐stranded, positive‐sense RNA virus. This gene product, designated as NbTRXh2, was matched with sequences of thioredoxin h proteins, a group of small proteins with a conserved active‐site motif WCXPC conferring disulfide reductase activity. To examine how NbTRXh2 is involved in the infection cycle of BaMV, we used the virus‐induced gene silencing technique to knock down NbTRXh2 expression in N. benthamiana and inoculated the plants with BaMV. We observed that, compared with control plants, BaMV coat protein accumulation increased in knockdown plants at 5 days post‐inoculation (dpi). Furthermore, BaMV coat protein accumulation did not differ significantly between NbTRXh2‐knockdown and control protoplasts at 24 hpi. The BaMV infection foci in NbTRXh2‐knockdown plants were larger than those in control plants. In addition, BaMV coat protein accumulation decreased when NbTRXh2 was transiently expressed in plants. These results suggest that NbTRXh2 plays a role in restricting BaMV accumulation. Moreover, confocal microscopy results showed that NbTRXh2‐OFP (NbTRXh2 fused with orange fluorescent protein) localized at the plasma membrane, similar to AtTRXh9, a homologue in Arabidopsis. The expression of the mutant that did not target the substrates failed to reduce BaMV accumulation. Co‐immunoprecipitation experiments revealed that the viral movement protein TGBp2 could be the target of NbTRXh2. Overall, the functional role of NbTRXh2 in reducing the disulfide bonds of targeting factors, encoded either by the host or virus (TGBp2), is crucial in restricting BaMV movement. [ABSTRACT FROM AUTHOR]

Objective: Different strategies for epithelial cell isolation significantly affect the viability and physiological properties of primary cells. Trypsin digestion, a conventional method, causes collateral damage owing to its strong digestive potential. To better preserve the physiological properties of epithelial tissues, we aimed to develop a modified method (hyaluronidase and collagenase I combination) for primary cell isolation. Method: We used conventional and modified methods to compare cell viability, morphology and stemness. Additionally, we investigated the passaging stability of epithelial cells and their capacity for organoid formation. Finally, we compared the two methods for isolating urothelial, oesophageal, lingual, and epidermal epithelial cells. Result: Gingival epithelial cells obtained using the modified method had higher viability, better morphology and stronger stemness than those obtained using the conventional method. Additionally, primary cells obtained using the modified method were stably passaged. Regarding organoid culture, adopting the modified method led to a significant increase in the growth rate and expression of the stem cell markers cytokeratin (CK)‐19 and Ki‐67. Furthermore, the modified method outperformed the conventional method for isolating urothelial, epidermal, oesophageal and lingual epithelial cells. Conclusion: We demonstrated that the combination of hyaluronidase and collagenase I outperformed trypsin in preserving the physiological properties of primary cells and organoid formation. The modified method could be broadly applied to isolate different types of epithelial cells and facilitate studies on organoids and tissue engineering. [ABSTRACT FROM AUTHOR]

Background β-Cells at different stages have different functions and capacity for proliferation, regenerative and apoptosis. The aim of the present study was to investigate whether there are changes in β-cell phonotype in the development of diabetes to identify potential β-cell targets to prevent the progression of diabetes. Methods A cross-sectional study was performed on pancreatic tissues obtained from 80 patients classified into three groups: 25 with type 2 diabetes ( T2D), 25 with impaired fasting glucose ( IFG), and 30 non-diabetics ( ND). The ratio of the insulin-positive area to pancreatic area was used as an indirect marker of β-cell mass. Insulin-positive duct cells and scattered β-cells were defined as newly generated β-cells, whereas insulin/neurogenin 3 (Ngn3), insulin/v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A ( MafA) and insulin/ P16 double-positive cells were defined as immature, mature, and senescent β-cells, respectively; Ki67 was used as a marker of cell proliferation, and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling ( TUNEL) was used as a marker of cell apoptosis. Data were analyzed using the Kruskal-Wallis test. Results There were no significant differences in β-cell mass, the prevalence of insulin-positive duct cells, scattered β-cells, or insulin/Ngn3, insulin/ MafA, and Insulin/Ki67 double-positive cells among groups. The incidence of insulin/ P16 double-positive cells was significantly higher in T2D than ND. β-Cell apoptosis was significantly higher in T2D and IFG than ND. Conclusion The senescence and apoptosis of β-cells may be involved in the course of diabetes. [ABSTRACT FROM AUTHOR]

Pentatricopeptide repeat ( PPR) proteins characterized by tandem arrays of a degenerate 35-amino-acid repeat belong to a large family of RNA-binding proteins that are involved in post-transcriptional control of organelle gene expression. PPR proteins are ubiquitous in eukaryotes, and particularly prevalent in higher plants. Schizosaccharomyces pombe has 10 PPR proteins. Among them, ppr3, ppr4, ppr6, and ppr10 participate in mitochondrial post-transcriptional processes and are required for mitochondrial electron transport chain ( ETC) function. In the present work, we showed that deletion of ppr3, ppr4, ppr6, or ppr10 led to apoptotic cell death, as revealed by DAPI and Annexin V- FITC staining. These mutants also exhibited elevated levels of reactive oxygen species ( ROS). RNA sequencing ( RNA-seq) and quantitative RT- PCR analyses revealed that deletion of ppr10 affected critical biological processes. In particular, a core set of genes involved in iron uptake and/or iron homeostasis was elevated in the Δ ppr10 mutant, suggesting an elevated level of intracellular iron in the mutant. Consistent with this notion, Δ ppr3, Δ ppr4, Δ ppr6, and Δ ppr10 mutants exhibited increased sensitivity to iron. Furthermore, the iron chelator, bathophenanthroline disulfonic acid, but not the calcium chelator EGTA, nearly restored the viabilities of Δ ppr3, Δ ppr4, Δ ppr6, and Δ ppr10 mutants, and reduced ROS levels in the mutants. These results show for the first time that deletion of a ppr gene leads to perturbation of iron homeostasis. Our results also suggest that disrupted iron homeostasis in Δ ppr3, Δ ppr4, Δ ppr6, and Δ ppr10 mutants may lead to an increase in the level of ROS and induction of apoptotic cell death in S. pombe. Database The RNA-seq data have been deposited in the National Center for Biotechnology Information ( NCBI) BioProject database (accession number SRP091623) and Gene Expression Omnibus ( GEO) database (accession number ). [ABSTRACT FROM AUTHOR]

On 31st December 2020, The National Science Library of the Chinese Academy of Sciences (CAS) released a list of 65 international scientific journals, all of them indexed by the Web of Science, that were said to be potentially in conflict with academic rigour. The list immediately influenced the publication patterns of Chinese researchers. A year later, on 31st December 2021, CAS released a revised and reduced list of 35 questionable journals and said the publishers in the meantime had reacted constructively and improved the procedures of their journals. This study aims to provide an understanding of the motivations and criteria behind the list, partly by reviewing Chinese policy documents and public debates, partly with a quantitative analysis to detect the relative importance of the criteria used to select the journals for the list. [ABSTRACT FROM AUTHOR]

Background and Purpose: As the only ionotropic receptor in the 5‐HT receptor family, the 5‐HT3 receptor (5‐HT3R) is involved in psychiatric disorders and its modulators have potential therapeutic effects for cognitive impairment in these disorders. However, it remains unclear how 5‐HT3Rs shape synaptic plasticity for memory function. Experimental Approach Extracellular as well as whole‐cell electrophysiological recordings were used to monitor hippocampal LTP and synaptic transmission in hippocampal slices in 5‐HT3AR knockout or 5‐HT3AR‐GFP mice. Immunocytochemistry, qRT‐PCR and western blotting were used to measure receptor expression. We also assessed hippocampal dependent cognition and memory, using the Morris water maze (MWM) and novel object recognition. Key Results: We found that 5‐HT3R dysfunction impaired hippocampal LTP in Schaffer collateral (SC)‐CA1 pathway in hippocampal slices, by facilitating GABAergic inputs in pyramidal cells. This effect was dependent on 5‐HT3Rs on axon terminals. It resulted from reduced expression and function of the cannabinoid receptor 1 (CB1R) co‐localized with 5‐HT3Rs on axon terminals, and then led to diminishment of tonic inhibition of GABA release by CB1Rs. Inhibition of CB1Rs mimicked the facilitation of GABAergic transmission by 5‐HT3R disruption. Consequently, mice with hippocampal 5‐HT3R disruption exhibited impaired spatial memory in MWM tasks. Conclusion and Implications: These results suggest that 5‐HT3Rs are crucial in enabling hippocampal synaptic plasticity via a novel CB1R‐GABAA‐dependent pathway to regulate spatial memory. [ABSTRACT FROM AUTHOR]

Summary: Background: Infantile‐onset inflammatory bowel disease can be caused by defects in interleukin‐10 signalling. The natural history and clinical outcomes of allogeneic haematopoietic stem cell transplantation, medical treatment and surgery have not been thoroughly described. Aims: This study evaluates disease progression and clinical outcome in patients with interleukin‐10 signalling deficiency. Methods: One hundred and nine patients with interleukin‐10 signalling deficiency were retrospectively reviewed from a single tertiary centre. The Kaplan‐Meier method was applied to calculate probabilities of survival and interval between transplant and stoma closure. Results: One hundred and nine patients were reviewed, and 102 patients were included in the survival analysis. One hundred and eight patients were identified with IL10RA mutations, and one patient harboured IL10RB mutation. Seventy‐three patients received haematopoietic stem cell transplantation. The overall survival after transplantation was 64.2% (95% confidence interval, 52.8 to 75.6), and without transplantation, it was 47.5% (95% confidence interval, 14.8 to 80.2, P = 0.47). The median timeframe between transplant and stoma closure was 19.6 months. The probability of survival was significantly lower in patients with perforation (P < 0.001), ileus (P = 0.038) and without thalidomide treatment (P < 0.001) among patients who did not receive haematopoietic stem cell transplantation. The survival probability was not associated with timeframe between transplant and onset, graft source and genotypes. Conclusions: The survival probability was not significantly different between patients with transplantation and the non‐transplanted patients. [ABSTRACT FROM AUTHOR]

Objective: To identify and compare the factors affecting the knowledge of, attitude towards and use of antibiotics between urban and rural residents in China.Methods: A total of 3631 urban and rural residents in Heilongjiang Province, China, were selected using random sampling. Questionnaires recorded demographic characteristics and participant knowledge of, attitude towards and use of antibiotics. The responses of rural and urban residents were compared, and logistic regression analysis was applied to identify the factors that may contribute to the knowledge of, attitude towards and use of antibiotics.Results: The majority of the participants (>60%) were aware that antibiotics could be used to treat bacterial infections and that bacteria could be resistant to antibiotics. However, only roughly half (40-60%) of the participants were aware that bacterial resistance to antibiotics had become a problem in China. Urban participants reported a more adequate knowledge of, attitude towards and use of antibiotics than rural participants. Logistic regression analysis indicated that urban residency, female gender and level of education were associated with knowledge of, attitude towards and use of antibiotics.Conclusions: Within our sample in Heilongjiang Province, the knowledge of, attitude towards and use of antibiotics were suboptimal in roughly half of all urban and rural residents, but better in urban than in rural residents. Targeted interventions to educate rural residents in particular may reduce the misuse of antibiotics. [ABSTRACT FROM AUTHOR]

A gene down‐regulated in Nicotiana benthamiana after bamboo mosaic virus (BaMV) infection had high identity to the nuclear‐encoded chloroplast ferredoxin NADP+ oxidoreductase gene (NbFNR). NbFNR is a flavoenzyme involved in the photosynthesis electron transport chain, catalysing the conversion of NADP+ into NADPH. To investigate whether NbFNR is involved in BaMV infection, we used virus‐induced gene silencing to reduce the expression of NbFNR in leaves and protoplasts. After BaMV inoculation, the accumulation of BaMV coat protein and RNA was significantly reduced. The transient expression of NbFNR fused with orange fluorescent protein (OFP) localized in the chloroplasts and elevated the level of BaMV coat protein. These results suggest that NbFNR could play a positive role in regulating BaMV accumulation. Expressing a mutant that failed to translocate to the chloroplast did not assist in BaMV accumulation. Another mutant with a catalytic site mutation could support BaMV accumulation to some extent, but accumulation was significantly lower than that of the wild type. In an in vitro replication assay, the replicase complex with FNR inhibitor, heparin, the RdRp activity was reduced. Furthermore, BaMV replicase was revealed to interact with NbFNR in yeast two‐hybrid and co‐immunoprecipitation experiments. Overall, these results suggest that NbFNR localized in the chloroplast with functional activity could efficiently assist BaMV accumulation. [ABSTRACT FROM AUTHOR]