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As a specific type of asthenoteratozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by composite abnormalities, including absent, short, coiled, angulation, and irregular-caliber flagella. Mutations in cilia- and flagella-associated protein 43 ( CFAP43 ) are one of the main causative factors of MMAF established to date. To identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations, we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing panel. After systematic analysis, seven mutations in CFAP43 , including five novel mutations and two previously reported mutations, were identified from four families and related to MMAF in an autosomal recessive pattern. Papanicolaou staining, immunofluorescence, and electronic microscopy further clarified the semen characteristics and abnormal sperm morphologies, including disorganized axonemal and peri-axonemal structures, of the CFAP43 -deficient men. The female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection, and one of them successfully gave birth to a healthy boy. This study significantly expands the mutant spectrum of CFAP43 , and together with the available information regarding male infertility and MMAF, provides new information for the genetic diagnosis and counseling of MMAF in the future., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Shift workers are at increased risk of obesity and metabolic diseases, but their eating patterns on work and non-workdays are understudied. We aimed to examine whether energy intake and macronutrient intake of day and night shift nurses were different during work and non-workdays. We used a mixed-methods approach to study food intake of shift working nurses from two hospitals during day and night shifts. Participants completed baseline questionnaires about eating behaviour, sleep, chronotype, mood and shift work disorder. Participants then completed a 4-d food diary which included a non-workday prior to the first shift, the first and last shift (either day or night) and the following non-workday. After completion of the food diaries, we used semi-structured interviews to explore the qualitative aspects of eating behaviours. Seventy-nine shift-working nurses participated in the study. Daily energy intake was not significantly different on work and non-workdays in day or night shift workers ( p  > 0.05). Whilst macronutrient consumption was also not different between day and night shift workers ( p  > 0.05), sugar intake was higher in day compared to night shift workers ( p  = 0.02) on the non-workday prior to the first workday. In qualitative interviews, participants reported their eating to be different on day and night shifts as well as work and non-workdays. Eating behaviour in day and night shift workers was highly influenced by food availability, convenience, peers, and family members. Nurses qualitatively report that night and day shifts result in them eating differently despite no statistically discernible difference in energy intake.

This paper investigates the clinical efficacy of an automatic mobile trainer for gait training in stroke patients. Neuro-Developmental Treatment (NDT) is a rehabilitation method for stroke patients that enhances motor learning through repeated practice. Despite the proven effectiveness of therapist-assisted NDT, it is labor-intensive and demands health resources. Therefore, we developed automatic trainers based on NDT principles to perform gait training. This paper modifies the mobile trainer's intervention patterns to improve the subject's longitudinal gait symmetry, lateral pelvic displacement symmetry, and pelvic rotation. We first invited ten healthy subjects to test the modified trainer and then recruited 26 stroke patients to undergo the same gait training. Longitudinal symmetry, lateral symmetry, and pelvic rotation were assessed before, during, and after the intervention. Most subjects show improvements in longitudinal symmetry, lateral symmetry, and pelvic rotation after using the trainer. These results confirm the trainer's effectiveness of the modified intervention schemes in helping clinical gait rehabilitation for stroke patients.

Non-polar m-plane GaN terahertz quantum cascade laser (THz-QCL) structures have been studied. One is traditional three-well resonant-phonon (RP) design scheme. The other is two-well phonon scattering injection (PSI) design scheme. The peak gains of 41.8 and 44.2 cm -1 have been obtained at 8.2 and 7.7 THz respectively at 300 K according to the self-consistent non-equilibrium Green's function calculation. Different from the usual GaAs two-well design, the upper and lower lasing levels are both ground states in the GaN quantum wells for the PSI scheme, mitigating the severe broadening effect for the excited states in GaN. To guide the fabrication of such devices, the doping effect on the peak gain has been analyzed. The two designs have demonstrated distinct doping density dependence and it is mainly attributed to the very different doping dependent broadening behaviors. The results reveal the possibility of GaN based THz-QCL lasing at room temperature., (© 2023. The Author(s).)

Objective and Design: Post-traumatic urethral stricture is a clinical challenge for both patients and clinicians. Targeting glutamine metabolism to suppress excessive activation of urethral fibroblasts (UFBs) is assumed to be a potent and attractive strategy for preventing urethral scarring and stricture., Material or Subjects: In cellular experiments, we explored whether glutaminolysis meets the bioenergetic and biosynthetic demands of quiescent UFBs converted into myofibroblasts. At the same time, we examined the specific effects of M2-polarized macrophages on glutaminolysis and activation of UFBs, as well as the mechanism of intercellular signaling. In addition, findings were further verified in vivo in New Zealand rabbits., Results: It revealed that glutamine deprivation or knockdown of glutaminase 1 (GLS1) significantly inhibited UFB activation, proliferation, biosynthesis, and energy metabolism; however, these effects were rescued by cell-permeable dimethyl α-ketoglutarate. Moreover, we found that exosomal miR-381 derived from M2-polarized macrophages could be ingested by UFBs and inhibited GLS1-dependent glutaminolysis, thereby preventing excessive activation of UFBs. Mechanistically, miR-381 directly targets the 3'UTR of Yes-associated protein (YAP) mRNA to reduce its stability at the transcriptional level, ultimately downregulating expression of YAP, and GLS1. In vivo experiments revealed that treatment with either verteporfin or exosomes derived from M2-polarized macrophages significantly reduced urethral stricture in New Zealand rabbits after urethral trauma., Conclusion: Collectively, this study demonstrates that exosomal miR-381 from M2-polarized macrophages reduces myofibroblast formation of UFBs and urethral scarring and stricture by inhibiting YAP/GLS1-dependent glutaminolysis., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Intense ultraviolet (UV) exposure can cause phototoxic reactions, such as skin inflammation, resulting in injury. UV is a direct cause of DNA damage, but the mechanisms underlying transcriptional regulation within cells after DNA damage are unclear. The bioinformatics analysis of transcriptome sequencing data from UV-irradiated and non-UV-irradiated skin showed that transcription-related proteins, such as HSF4 and COIL, mediate cellular response to UV irradiation. HSF4 and COIL can form a complex under UV irradiation, and the preference for binding target genes changed because of the presence of a large number of R-loops in cells under UV irradiation and the ability of COIL to recognize R-loops. The regulation of target genes was altered by the HSF4-COIL complex, and the expression of inflammation and ageing-related genes, such as Atg7, Tfpi, and Lims1, was enhanced. A drug screen was performed for the recognition sites of COIL and R-loop. N6-(2-hydroxyethyl)-adenosine can competitively bind COIL and inhibit the binding of COIL to the R-loop. Thus, the activation of downstream inflammation-related genes and inflammatory skin injury was inhibited., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Cross protection application of HA5-1, an attenuated mutant of papaya ringspot virus (PRSV) HA strain from Hawaii, was withdrawn from Taiwan due to the narrow geographic strain specificity of HA5-1. Here, to overcome this problem, we created attenuated mutants of PRSV YK, a dominant severe strain from Taiwan, by mutating helper component protease (HC-Pro) at F 7 , R 181 , F 206 , and D 397 residues critical for potyviral pathogenicity. PRSV YK HC-Pro R 181 I, F 206 L, and D 397 N single-mutant viruses induced mild symptoms, but their adverse effects on growth of papaya plants disqualified them as useful protective viruses. However, F 7 I single-mutant and F 7 I + F 206 L double-mutant viruses displayed mild symptoms followed by recovery, and they showed a zigzag pattern of accumulation in papaya plants, indicating their potential to trigger RNA silencing and retain partial antagonistic suppression of host defense. Although F 7 I + R 181 I and F 7 I + D 397 N double-mutant viruses caused symptomless infection, they accumulated barely above mock level and, thus, were not qualified as proper protective viruses. RNA silencing suppression (RSS) analysis by agroinfiltration in Nicotiana benthamiana plants revealed that the HC-Pro F 7 I and F 7 I + F 206 L mutant proteins were weaker in RSS ability than the wild-type protein. Under greenhouse conditions, F 7 I and F 7 I + F 206 L mutant viruses were genetically stable but not aphid transmissible. Compared with the HA5-1 mutant's low degree (10%) of protection to papaya plants, the F 7 I and F 7 I + F 206 L mutants provided complete (100%) protection to papaya and horn melon plants against strain YK. Thus, F 7 I and F 7 I + F 206 L mutants solve the problem of strain-specific protection and have great potential for control of PRSV in Taiwan., Competing Interests: The author(s) declare no conflict of interest.

Background/objectives: Shift work has been linked to unhealthy eating behaviors such as imbalanced diet, or increased empty calorie food/beverage consumption. However, most research has focused on the impact of shift timing. The concept of shift work is complex, and it contains several domains such as shift timing, intensity, and speed. Previous studies have suggested that greater shift intensity and quicker shift speed may contribute to adverse health effects. However, evidence regarding associations between other domains of shift work and empty calorie food/beverage consumption has been relatively lacking. Therefore, the purpose of this study was to evaluate how other shift work domains related to empty calorie food/beverage consumption and whether different shift work domains interacted to influence the intake of foods or beverages., Design: A 14-day intensive longitudinal study employing ecological momentary assessment., Settings and Participants: Eighty registered nurses working in 24 accredited Taiwanese hospitals (i.e., 9 medical centers, 12 regional hospitals, and 3 district hospitals) were recruited., Methods: During the study period, a convenience sample of 77 participants completed 2444 momentary surveys about empty calorie food/beverage consumption on a smartphone. Three shift work domains (shift timing, intensity, and speed) were evaluated based on registry-based work schedules. To study how these shift work domains influenced empty calorie food/beverage consumption, we employed three-level mixed-effects regression models for data analyses., Results: Findings suggested that greater night shift intensity increased the likelihood of sugar-sweetened beverage intake (odds ratio = 1.64, 95% confidence interval [1.01, 2.68]). The impacts of work shift intensity and shift timing on sugar-sweetened beverage consumption varied by shift speed. Among participants assigned a schedule with either medium or rapid shift speed, higher work shift intensity was associated with a higher probability of sugar-sweetened beverage consumption. Compared to day shifts, those who were assigned a quicker shift speed on evening shifts were more likely to consume sugar-sweetened beverages. However, associations between night shift intensity and sugar-sweetened beverage intake did not change by shift speed. Furthermore, shift intensity and shift timing did not interact to affect empty calorie food/beverage consumption., Conclusions: This study demonstrated assignments of shift schedules (i.e., high night shift intensity, more changes in shift timings) might influence workers' consumption of empty calorie foods/beverages. Therefore, identifying and mitigating hazardous shift schedules may help to improve shift workers' eating behaviors and benefit their overall health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Because of the growing number of clinical antibiotic resistance cases in recent years, novel antimicrobial peptides (AMPs) may be ideal for next-generation antibiotics. This study trained a Wasserstein generative adversarial network with gradient penalty (WGAN-GP) based on known AMPs to generate novel AMP candidates. The quality of the GAN-designed peptides was evaluated in silico, and eight of them, named GAN-pep 1-8, were selected by an AMP Artificial Intelligence (AI) classifier and synthesized for further experiments. Disc diffusion testing and minimum inhibitory concentration (MIC) determinations were used to identify the antibacterial effects of the synthesized GAN-designed peptides. Seven of the eight synthesized GAN-designed peptides displayed antibacterial activity. Additionally, GAN-pep 3 and GAN-pep 8 presented a broad spectrum of antibacterial effects and were effective against antibiotic-resistant bacteria strains, such as methicillin-resistant Staphylococcus aureus and carbapenem-resistant Pseudomonas aeruginosa . GAN-pep 3, the most promising GAN-designed peptide candidate, had low MICs against all the tested bacteria. In brief, our approach shows an efficient way to discover AMPs effective against general and antibiotic-resistant bacteria strains. In addition, such a strategy also allows other novel functional peptides to be quickly designed, identified, and synthesized for validation on the wet bench.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of chemotherapy and remains a huge clinical challenge. Here, we explore the role of microcirculation hypoxia induced by neutrophil extracellular traps (NETs) in the development of CIPN and look for potential treatment., Methods: The expression of NETs in plasma and dorsal root ganglion (DRG) are examined by ELISA, IHC, IF and Western blotting. IVIS Spectrum imaging and Laser Doppler Flow Metry are applied to explore the microcirculation hypoxia induced by NETs in the development of CIPN. Stroke Homing peptide (SHp)-guided deoxyribonuclease 1 (DNase1) is used to degrade NETs., Findings: The level of NETs in patients received chemotherapy increases significantly. And NETs accumulate in the DRG and limbs in CIPN mice. It leads to disturbed microcirculation and ischemic status in limbs and sciatic nerves treated with oxaliplatin (L-OHP). Furthermore, targeting NETs with DNase1 significantly reduces the chemotherapy-induced mechanical hyperalgesia. The pharmacological or genetic inhibition on myeloperoxidase (MPO) or peptidyl arginine deiminase-4 (PAD4) dramatically improves microcirculation disturbance caused by L-OHP and prevents the development of CIPN in mice., Interpretation: In addition to uncovering the role of NETs as a key element in the development of CIPN, our finding provides a potential therapeutic strategy that targeted degradation of NETs by SHp-guided DNase1 could be an effective treatment for CIPN., Funding: This study was funded by the National Natural Science Foundation of China81870870, 81971047, 81773798, 82271252; Natural Science Foundation of Jiangsu ProvinceBK20191253; Major Project of "Science and Technology Innovation Fund" of Nanjing Medical University2017NJMUCX004; Key R&D Program (Social Development) Project of Jiangsu ProvinceBE2019732; Nanjing Special Fund for Health Science and Technology DevelopmentYKK19170., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Prostate cancer (PCa) is the second leading cause of male cancer-related deaths in the United States. The pre-mature forms of prostate-specific antigen (PSA), proPSA, were shown to be associated with PCa. However, there is a technical challenge in the development of antibody-based immunoassays for specific recognition of each individual proPSA isoform. Herein, we report the development of highly specific, antibody-free, targeted mass spectrometry assays for simultaneous quantification of [-2], [-4], [-5], and [-7] proPSA isoforms in voided urine. The newly developed proPSA assays capitalize on Lys-C digestion to generate surrogate peptides with appropriate length (9-16 amino acids) along with long-gradient liquid chromatography separation. The assay utility of these isoform markers was evaluated in a cohort of 30 well-established clinical urine samples for distinguishing PCa patients from healthy controls. Under the 95% confidence interval, the combination of [-2] and [-4] proPSA isoforms yields the area under curve (AUC) of 0.86, and the AUC value for the combined all four isoforms was calculated to be 0.85. We have further verified [-2]proPSA, the dominant isoform, in an independent cohort of 34 clinical urine samples. Validation of proPSA isoforms in large-scale cohorts is needed to demonstrate their potential clinical utility.

Cancers are caused by accumulated DNA mutations. This recognition of the central role of mutations in cancer and recent advances in next-generation sequencing, has initiated the massive screening of clinical samples and the identification of 1000s of cancer-associated gene mutations. However, proteomic analysis of the expressed mutation products lags far behind genomic (transcriptomic) analysis. With comprehensive global proteomics analysis, only a small percentage of single nucleotide variants detected by DNA and RNA sequencing have been observed as single amino acid variants due to current technical limitations. Proteomic analysis of mutations is important with the potential to advance cancer biomarker development and the discovery of new therapeutic targets for more effective disease treatment. Targeted proteomics using selected reaction monitoring (also known as multiple reaction monitoring) and parallel reaction monitoring, has emerged as a powerful tool with significant advantages over global proteomics for analysis of protein mutations in terms of detection sensitivity, quantitation accuracy and overall practicality (e.g., reliable identification and the scale of quantification). Herein we review recent advances in the targeted proteomics technology for enhancing detection sensitivity and multiplexing capability and highlight its broad biomedical applications for analysis of protein mutations in human bodily fluids, tissues, and cell lines. Furthermore, we review recent applications of top-down proteomics for analysis of protein mutations. Unlike the commonly used bottom-up proteomics which requires digestion of proteins into peptides, top-down proteomics directly analyzes intact proteins for more precise characterization of mutation isoforms. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large-scale targeted detection and quantification of important protein mutations are discussed., (© 2021 John Wiley & Sons Ltd.)

Objective: This study aimed to identify potential biomarkers for prostate cancer (PCa) progression and metastasis, and to discern their biological functions., Methods: Bioinformatics methods were used to screen for hub genes. The expression level of key hub genes in PCa was determined and their prognostic significance was examined. A series of functional assays were performed to investigate the function of the highest-ranking hub gene., Results: Actin related protein 2/3 complex subunit 1A (ARPC1A) was identified as the hub gene. ARPC1A was highly expressed in PCa tissues and cell lines, and was an independent prognostic factor for predicting biochemical recurrence after radical prostatectomy and overall survival of PCa patients. Knockdown of ARPC1A inhibited PCa cell migration, invasion and cytoskeleton formation, but had no impact on cell proliferation and cell cycle progression. In vivo, ARPC1A overexpression promoted lung metastasis of PCa, but had no efffect on tumor growth. Additionally, glutamine metabolism was identified as an upstream regulator of ARPC1A, and promoted migration, invasion and cytoskeletal changes of PCa cell through ARPC1A., Conclusion: These findings suggested that ARPC1A, which correlates with poor prognosis in PCa, functions downstream of glutamine metabolism to regulate cytoskeletal changes, cellular migration and cellular invasion in this disease., (© 2023. The Author(s).)

Aim: To evaluate the differences between human lacrimal gland adenoid cystic carcinoma with high-grade transformation (LACC-HGT) primary cells cultured by high-grade transformation tissue and non-high-grade transformation (non-HGT) primary cells cultured by non-high-grade transformation tissue in proliferation, metastasis, drug susceptibility, and genes., Methods: LACC-HGT primary cells were established by tissue block culture, and the 4 th to 10 th generation primary cells were selected as research objects. The cells were preliminarily identified by immunofluorescent staining. The differences between non-HGT and LACC-HGT primary cells in terms of proliferation, metastasis, and drug susceptibility were compared by cell counting kit-8 (CCK-8) assay, wound healing, and drug sensitivity experiments. Differentially expressed genes were screened using mRNA array. Gene expression was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR)., Results: LACC-HGT primary cells were successfully cultured by tissue block culture. Immunofluorescence staining results showed that cytokeratin (CK) and CK7 expression levels were positive in LACC-HGT primary cells. CCK-8 results showed that the proliferation ability of LACC-HGT cells was significantly higher than that of non-HGT cells. Wound healing experiment showed that the migration ability of LACC-HGT cells was significantly higher than that of non-HGT cells. LACC-HGT cells were also less sensitive to cisplatin and paclitaxel than non-HGT cells. Compared with non-HGT cells, 9566 differentially expressed genes were found in LACC-HGT primary cells, of which 5162 were up-regulated and 4404 were down-regulated. The expression of N-acetylneuraminate pyruvate lyase (NPL), MARVEL domain containing 3 (MARVELD3), syntabulin (SYBU), and allograft inflammatory factor 1 (AIF1) was higher in LACC-HGT cells than in non-HGT cells, whereas that of periostin (POSTN) was lower., Conclusion: LACC-HGT primary cells have faster proliferation, stronger migration ability, and poorer sensitivity to chemotherapy drugs than non-HGT primary cells. The expression of mRNAs in non-HGT and LACC-HGT primary cells are significantly different. These features are speculated to be the reasons why high-grade transformation tissues exhibit higher malignant degree and poorer prognosis than their counterparts., (International Journal of Ophthalmology Press.)

Weekend effect has been considered to be associated with poorer quality of care and patient's survival. For acute myocardial infarction (AMI) patients, the question of whether patients admitted during off-hours have worse outcomes as compared with patients admitted during on-hours is still inconclusive. We conducted this study to explore the weekend effect in AMI patients, using a nationwide insurance database in Taiwan. Using Taiwan National Health Insurance (NHI) claims database, we designed a retrospective cohort study, and extracted 184,769 incident cases of AMI through the NHI claims database between January 2006 and December 2014. We divided the patients into weekend admission group and weekday admission group. Patients were stratified as ST elevation/non-ST elevation AMI and receiving/not receiving percutaneous coronary intervention (PCI). We used a logistic regression model to examine the relative risk of in-hospital mortality and 1-year mortality which were obtained from the Taiwan National Death Registry between study groups. We found no difference between weekend group and weekday group for risk of in-hospital mortality (15.8% vs 16.2%, standardized difference 0.0118) and risk of 1-year mortality (30.2% vs 30.9%, standardized difference 0.0164). There was no statistically significant difference among all the comparisons through the multivariate logistic regression analysis adjusting for all the covariates and stratifying by the subtypes of AMI and whether or not executing PCI during hospitalization. As for AMI patients in Taiwan, admission on weekends or weekdays did not have a significant impact on either in-hospital mortality or 1-year cumulative mortality., (© 2023. The Author(s).)

On-site nucleic acid testing (NAT) plays an important role for disease monitoring and pathogen diagnosis. In this work, we developed an automated and fully-integrated nucleic acid analyzer by combining the automated liquid handling robot technique with the microfluidic droplet-based real-time PCR assay technique. The present analyzer could achieve multiple operations including sample introduction, nucleic acid extraction based on magnetic solid-phase extraction, reverse transcription and, sample droplet generation, PCR amplification, real-time and dual fluorescence detection of droplet array. A strategy of constructing an integrated compact and low-cost system was adopted to minimize the analyzer size to 50 × 45 × 45 cm (length × width × height), and reduce the instrument cost to ca. $900 with a single analysis cost less than $5. A simple chip was also designed to pre-load reagents and carry oil-covered PCR reaction droplets. We applied the analyzer to identify eight types of influenza pathogens in human throat swabs, and the results were consistent with the colloidal gold method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The parabrachial nucleus (PBN) is an important structure regulating the sleep-wake behavior and general anesthesia. Astrocytes in the central nervous system modulate neuronal activity and consequential behavior. However, the specific role of the parabrachial nucleus astrocytes in regulating the sleep-wake behavior and general anesthesia remains unclear. Methods: We used chemogenetic approach to activate or inhibit the activity of PBN astrocytes by injecting AAV-GFAabc1d-hM3Dq-eGFP or AAV-GFAabc1d-hM4Di-eGFP into the PBN. We investigated the effects of intraperitoneal injection of CNO or vehicle on the amount of wakefulness, NREM sleep and REM sleep in sleep-wake behavior, and on the time of loss of righting reflex, time of recovery of righting reflex, sensitivity to isoflurane, electroencephalogram (EEG) power spectrum and burst suppression ratio (BSR) in isoflurane anesthesia. Results: The activation of PBN astrocytes increased wakefulness amount for 4 h, while the inhibition of PBN astrocytes decreased total amount of wakefulness during the 3-hour post-injection period. Chemogenetic activation of PBN astrocytes decreased isoflurane sensitivity and shortened the emergence time from isoflurane-induced general anesthesia. Cortical EEG recordings revealed that PBN astrocyte activation decreased the EEG delta power and BSR during isoflurane anesthesia. Chemogenetic Inhibition of PBN astrocytes increased the EEG delta power and BSR during isoflurane anesthesia. Conclusion: PBN astrocytes are a key neural substrate regulating wakefulness and emergence from isoflurane anesthesia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Yao, Chen, Su, Zheng, Yan, Deng, Shi, Liu, Gao, Lin, Zhu, Lin, Zhu, Cai, Zhang and Chen.)

Background and Purpose: The implantation of carotid artery stents prevents recurrent ischemic stroke in patients with carotid stenosis. This study aimed to investigate associations between change of ophthalmic artery flow (COAF) post carotid stenting and recurrent ischemic stroke, as well as the link toward the anterior and posterior circulations and patients' prognosis after carotid stenting., Methods: This retrospective, longitudinal cohort study recruited 87 left side carotid stenosed ischemic stroke patients undergoing left side carotid stenting between year of 2009 and 2013, and patients were followed up to 9 years after carotid procedures. Clinical data were derived from medical records. The primary outcome was stroke recurrence. Predictive factors were stenosis  > 50% in one intracranial artery and ROAF. Kaplan-Meier and Cox regression analyses were used to identify risk factors associated with stroke recurrence., Results: Among 87 included patients undergone left side carotid stent treatment, 44 had stroke recurrence within 3 years after carotid stenting. The recurrence group had significantly greater proportions of COAF after stenting (p = 0.001), and middle cerebral artery (MCA) and basilar artery or vertebral artery (BA/VA) stenosis > 50% (all p < 0.001) than the no-recurrence group. Survival was significantly shorter in patients with COAF than in those without (p < 0.01). Regression analysis showed that COAF was associated with stroke recurrence (HR: 3.638, 95% CI 1.54-8.62, p = 0.003). The recurrence rate was highest in patients with bilateral MCA stenosis  > 50% (100%), followed by left MCA stenosis  > 50% plus BA/VA stenosis  > 50% (83.33%) or COAF (82.14%). Patients with bilateral MCA stenosis  < 50% had no recurrence within 3-year follow-up., Conclusions: Prognosis after carotid stenting is poorer for patients with MCA stenosis  > 50%, BA/VA stenosis  > 50% and/or COAF. Carotid duplex and magnetic resonance angiography provide definitive information for prognosis prediction., (© 2022. The Author(s).)

Objective: This study was to explore the risk factors for postoperative bladder neck contracture (BNC) after transurethral operation of prostate in patients with small-volume prostatic obstruction., Methods: Clinicopathologic data at our center from February 2016 to January 2020 were retrospectively collected and analyzed. Clinicopathological characteristics between patients with and without BNC were compared. Multivariate logistic regression was used to determine the risk factors for postoperative BNC., Results: There were a total of 39 patients (8.53%) with postoperative BNC. Multivariate logistic regression analysis demonstrated that preoperative bladder neck diameter (BND), intravesical prostatic protrusion (IPP), surgical methods (transurethral resection of prostate (TURP)/anatomical endoscopic enucleation of the prostate (AEEP)), and postoperative urinary tract infection (UTI) were independent risk factors for postoperative BNC in patients with small-volume prostatic obstruction (P < 0.05). The incidence of postoperative BNC in patients undergoing AEEP was significantly decreased compared with those undergoing TURP. The optimal cut-off value of preoperative IPP was 6.10 mm while the optimal cut-off value of preoperative BND was 2.52 cm., Conclusions: Larger preoperative bladder neck and higher preoperative IPP lead to decreased incidence of postoperative BNC in patients with small-volume prostatic obstruction. Active management of postoperative UTI could effectively prevent the occurrence of postoperative BNC. Compared with TURP, complete AEEP would contribute to reduce BNC in patients with small-volume prostatic obstruction., Competing Interests: Declaration of competing interest Not applicable., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest Dr Tao Liu was employed by Beijing Novartis Pharma Company Limited. Drs Ruan, Zhang, Zhuo Liu, Lin, Wang, Xu, Xiang, Cheng, Ha, Gong, and Ji have no conflicts of interest to declare.

The recent designs of terahertz quantum cascade lasers usually employ the short periodic length and also the tall barriers for high-temperature operation. In this work, the effect of high-energy lying non-relevant subbands is studied based on nonequilibrium Green's function formalisms model, demonstrating those subbands are probable to play a minor role on the population inversion, but play a major role on the optical gain at high temperatures. The phenomenon can be ascribed to the appearance of leakages crossing neighboring periods via sequential resonant tunneling, and those leakages are inherently created by the specific features of the two-well configuration in this design that the phonon well should be wide enough for performing the phonon scattering to depopulate the lower-laser subband. The narrower periodic length design can strengthen this inter-period leakage. A parasitic absorption between the first high-lying nonrelevant subbands from two laser wells can closely overlap the gain shape and thus significantly reduce the peak gain., (© 2022. The Author(s).)

The phenomenon of cross adaptation refers to the ability of plants to improve their resistance to other stress after experiencing one type of stress. However, there are limited reports on how ultraviolet radiation B (UVB) pretreatment affects the enrichment, transport, and tolerance of cadmium (Cd) in plants. Since an appropriate UVB pretreatment has been reported to change plant tolerance to stress, we hypothesized that this application could alter plant uptake and tolerance to heavy metals. In this study, a woody plant species, 84K poplar ( Populus alba × Populus glandulosa ), was pretreated with UVB and then subjected to Cd treatment. The RT-qPCR results indicated that the UVB-treated plants could affect the expression of Cd uptake, transport, and detoxification-related genes in plants, and that the UVB-Pretreatment induced the ability of Cd absorption in plants, which significantly enriched Cd accumulation in several plant organs, especially in the leaves and roots. The above results showed that the UVB-Pretreatment further increased the toxicity of Cd to plants in UVB-Cd group, which was shown as increased leaf malonaldehyde (MDA) and hydrogen peroxide (H 2 O 2 ) content, as well as downregulated activities of antioxidant enzymes such as Superoxide Dismutase (SOD), Catalase (CAT), and Ascorbate peroxidase (APX). Therefore, poplar plants in the UVB-Cd group presented a decreased photosynthesis and leaf chlorosis. In summary, the UVB treatment improved the Cd accumulation ability of poplar plants, which could provide some guidance for the potential application of forest trees in the phytoremediation of heavy metals in the future.

This study investigates gait symmetry and single-leg stance balance of professional yoga instructors versus age-matched typically developed controls using inertial measurement unit (IMU)-based evaluation. We recruited twenty-five yoga instructors and twenty-five healthy control subjects to conduct the walking experiments and single-leg stance tests. Kinematic data were measured by attaching IMUs to the lower limbs and trunk. We assessed the asymmetry of swing phases during the normal-walk and tandem-walk tests with eyes open and closed, respectively. The subjects subsequently conducted four single-leg stance tests, including a single-leg stance on both legs with eyes open and closed. Two balance indexes regarding the angular velocities of the waist and chest were defined to assess postural stability. The gait asymmetry indexes of yoga instructors were significantly lower than those of the typically developed controls. Similarly, the yoga instructors had better body balance in all four single-leg stance tests. This study's findings suggest that yoga improves gait asymmetry and balance ability in healthy adults. In the future, further intervention studies could be conducted to confirm the effect of yoga training.

Background: Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk., Methods: This prospective cohort study included 3928 adults aged ≥ 55 years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis., Results: Of the 3928 participants (mean age: 69 years; 2060 [52%] were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval [CI], 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR [95% CI], 1.27 [1.16 to 1.38]) and after excluding those with serum high-sensitivity C-reactive protein above 10 mg/L (HR [95% CI], 1.21[1.11 to 1.31]) or 3 mg/L (HR [95% CI], 1.19 [1.06 to 1.31]) during follow-up., Conclusions: A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death., (© 2022. The Author(s).)

Background: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. Success is associated with autonomic function modulation; however, the relationship between the changes after ablation is not fully understood. We aimed to investigate the effect of ablation on autonomic modulation by skin sympathetic nerve activity (SKNA) using conventional electrocardiogram (ECG) electrodes and to predict the treatment success., Methods: We enrolled 79 patients. We recorded neuECG for 10 min at 10 kHz before and after ablation. The NeuECG was bandpass-filtered (500-1,000 Hz) and integrated at intervals of 100 ms (iSKNA). iSKNA was averaged over different time windows (1-, 5-,10-s; aSKNAs), and burst analyses were derived from aSKNAs to quantify the dynamics of sympathetic activities. AF recurrence after 3 months was defined as the study endpoint., Results: Sixteen patients experienced AF recurrence after the ablation. For burst analysis of 1-s aSKNA, the recurrence group had a higher bursting frequency than the non-recurrence group (0.074 ± 0.055 vs. 0.109 ± 0.067; p < 0.05) before ablation. The differences between pre- and post-ablation of firing duration longer than 2 s were more in the non-recurrence group (2.75 ± 6.41 vs. -1.41 ± 5.14; p < 0.05), while no significant changes were observed in the percentage of duration longer than 10 s using 5-s aSKNA. In addition, decreases in differences in firing frequency and percentage of both overall firing duration and longer firing duration (> 2 s) between pre- and post-ablation were independently associated with AF recurrence and more area under receiver operating characteristics (ROC) curve in combination with CHADS 2 score (0.833)., Conclusion: We demonstrated the applicability of neuECG for determining sympathetic modulation during AF ablation. Decreasing sympathetic activity is the key to successful ablation., 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 Chen, Lin, Chuang, Lee, Lin, Yu, Tsai, Liao, Lin, Lin and Lo.)

Left atrial appendage (LAA) closure (LAAC) device implantation may be challenging in cases with difficult LAA anatomy. A deflectable sheath to approach multiple LAA positions may be helpful. We used a deflectable sheath to implant LAAC devices in 20 patients and included 60 cases using the standard sheaths for comparison. The procedures were successful in all patients without peri-procedural complications. After a median follow-up of 1.52 (IQR: 0.76-2.33) years, none of the patients in the deflectable sheath group had peri-device leak ≥3 mm and experienced thromboembolic stroke. In the standard sheath group, after follow-up of 2.03 (IQR: 0.87-3.19) years, 2 had peri-device leak ≥3 mm and 1 experienced thromboembolic stroke. We first proved the idea of using a universal steerable sheath for LAAC device implantation in difficult LAA anatomy, which also allows rapid switching of different LAAC devices., Competing Interests: The work was supported by grants from the Ministry of Science and Technology in Taiwan (MOST 109-2314-B-002-244-MY3 and MOST 110-2314-B-002-198 -MY3). The Ministry of Science and Technology had no role in the conduct of this study. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Objective: In patients with non-valvular atrial fibrillation (NVAF), the left atrial appendage occluder (LAAO) is an alternative treatment for stroke prevention. However, thromboembolic event still occur, and the predictors are unknown., Methods: The first Asian long-term follow-up study consisted of 308 patients with mean age 71.9±9.5 years, mean CHA 2 DS 2 -VASc 4.1 ± 1.8 since 2013. Primary outcome was defined as any type of ischemic stroke/transient ischemic attack (TIA), systemic embolization and cardiovascular death., Results: There was no procedural-related TIA or stroke. After a mean follow-up of 38±16 months, the ischemic stroke/TIA rate was 1.9 and cardiovascular death rate 0.3 per 100 patient-year. The rate of peri-device leak (PDL) was 11.9% and device-related thrombus (DRT) 2.6%. In the multivariable analyses, PDL was the only independent predictor of stroke/TIA (hazard ratio 5.5, p=0.008). CHA 2 DS 2 -VASc score, prior history of stroke, DRT and post-procedural anti-thrombotic regimen/duration were not associated with outcomes. Implantation of Watchman was associated with PDL (odds ratio 4.35, p=0.001)., Conclusions: PDL is the only independent predictor of post-LAAO stroke. The risk of stroke for patients with NVAF may be controllable after LAA is occluded, because PDL is preventable and treatable., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: To compare nurses' non-optimal eating behaviours across different shifts, to examine whether non-day shifts were related to deviation from optimal dietary behaviours compared with day shifts and whether such deviation was related to non-optimal macronutrient intake., Design: This is a 4-day intensive longitudinal study., Methods: A convenience sample of hospital nurses was recruited in Taiwan. From September 2018 through January 2019, 120 participants completed 4-days of 24-h dietary recalls. One-way ANOVA and Kruskal-Wallis H test were used to compare differences in energy and macronutrient intake and frequency of meals and snacking, respectively. Generalized linear regressions examined (1) the associations between shiftwork schedules and non-optimal eating behaviours and (2) associations between non-optimal eating and high energy contribution of non-optimal macronutrients., Results: Nurses consumed less energy on evening and night shifts compared with day shifts. However, energy intake from snacking was higher on evening and night shifts relative to day shifts. Nurses consumed less meals but had higher snacking frequency on non-day shifts. In addition, high energy intake from snacking was positively associated with high energy intake from saturated fat., Conclusions: Nurses were more likely to have non-optimal eating behaviours on non-day shifts, which may contribute to an increased intake of saturated fat; thus, increasing their risk of chronic diseases. Strategies to improve non-day shift nurses' non-optimal eating behaviours may be beneficial to their health., Impact: Shiftwork is known to affect nurses' eating behaviours; however, which shift is associated with unhealthy eating remains inconclusive. Despite lower energy intakes, nurses had higher intake by snacking on evening and night shifts. High snacking intake was associated with a high intake of saturated fat. Hospitals can increase the availability of healthy foods on evening or night shifts, which may improve non-day shift nurses' non-optimal eating behaviours., (© 2022 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background: Rapid developments in medical care-such as monitoring devices, medications, and working hours restrictions for intensive care personnel-have dramatically increased the demand for intensive care physicians. Therefore, nurse practitioner (NP)-staffed care is becoming increasingly important. This study was aimed to compare the outcomes of daytime NP-staffed and daytime resident-staffed nonsurgical intensive care units (ICU)., Methods: We retrospectively assessed patients admitted to a nonsurgical ICU from March 2017 to December 2017. We collected basic patient data, including age, sex, admission diagnosis, transferring unit, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Primary endpoints were ICU mortality, hospital mortality, and 30-day mortality. Secondary endpoints were 48-h readmission, discharge to nonhome locations, and lengths of ICU and hospital stay., Results: A total of 838 subjects were analysed: 334 subjects in the NP-staffed group and 504 in the resident-staffed group. The NP-staffed group was more likely to come from inpatient units (38.3% vs 16.5% for resident-staffed group; p &lt; 0.001) and had lower disease severity (APACHE II score, 13.9 ± 8.4 vs 15.1 ± 8.2 for resident-staffed group; p = 0.047). After adjusting for age, sex, location before ICU admission, APACHE II score, and significantly different basic characteristics, there were no differences in ICU mortality, hospital mortality, or 30-day mortality between the two groups. Secondary analysis showed the NP-staffed group had a lower discharge rate to nonhome locations (2.1% vs 6.3%; p = 0.023) and shorter hospital stay (12.1 ± 14.1 vs 14.2 ± 14.3 days; p = 0.015)., Conclusions: We observed no difference in mortality between daytime NP-staffed and resident-staffed nonsurgical ICUs. Daytime NP-staffed care is an effective, safe, feasible method for staffing nonsurgical ICUs., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Motivation: Antiviral peptides (AVPs) from various sources suggest the possibility of developing peptide drugs for treating viral diseases. Because of the increasing number of identified AVPs and the advances in deep learning theory, it is reasonable to experiment with peptide drug design using in silico methods., Results: We collected the most up-to-date AVPs and used deep learning to construct a sequence-based binary classifier. A generative adversarial network was employed to augment the number of AVPs in the positive training dataset and enable our deep learning convolutional neural network (CNN) model to learn from the negative dataset. Our classifier outperformed other state-of-the-art classifiers when using the testing dataset. We have placed the trained classifiers on a user-friendly web server, AI4AVP, for the research community., Availability and Implementation: AI4AVP is freely accessible at http://axp.iis.sinica.edu.tw/AI4AVP/; codes and datasets for the peptide GAN and the AVP predictor CNN are available at https://github.com/lsbnb/amp&#95;gan and https://github.com/LinTzuTang/AI4AVP&#95;predictor., Supplementary Information: Supplementary data are available at Bioinformatics Advances online., (© The Author(s) 2022. Published by Oxford University Press.)

Recent renewed operating temperatures in terahertz quantum cascade lasers emphasize on narrowing the periodic length in a 2-well resonant-phonon design for a clean quantum level structure, in which the depopulation energy is significantly higher than one longitudinal phonon. In this study, various depopulation energies (small and large) are engineered in a 2-well design; the effect of the high-lying nonrelevant levels on the currents are systematically studied by using the non-equilibrium Green's function method. The engineering of the depopulation energy is unable to avoid the formation of leakage channels, which are activated within at least three neighboring periods via sequential close tunneling. However, a large depopulation energy relaxes the thermal backfilling process; as a result, the net leakages at high temperatures can be significantly suppressed. In addition, pre-alignment remains a critical issue in the design when using a large depopulation energy, which requires improved engineering for the barriers to obtain better laser dynamics., (© 2022. The Author(s).)

In this work, the microstructure and mechanical properties of atmospheric plasma-sprayed coatings of Al 0.5 CoCrFeNi 2 Ti 0.5, prepared using gas-atomized powders at varying spray powers, are studied in as-sprayed and heat-treated conditions. Gas-atomized powders had spherical shapes and uniform element distributions, with major FCC phases and metastable BCC phases. The metastable BCC phase transformed to ordered and disordered BCC phases when sufficient energy was applied during the plasma-spraying process. During the heat treatment process for 2 hrs, disordered BCCs transformed into ordered BCCs, while the intensity of the FCC peaks increased. Spraying power plays a significant role in the microstructure and mechanical properties of plasma sprayed because at a high power, coatings exhibit better mechanical properties due to their dense microstructures resulting in less defects. As the plasma current was increased from 500 A to 700 A, the coatings' hardness increased by approximately 21%, which is directly proportional to the decreased wear rate of the coatings at high spraying powers. As the coatings experienced heat treatments, the coatings sprayed with a higher spraying power showed higher hardness and wear resistances. Precipitation strengthening played a significant role in the hardness and wear resistances of the coatings due to the addition of the titanium element.

Background: Main bottleneck in facilitating integrated pest management (IPM) is the unavailability of reliable and immediate crop damage data. Without sufficient insect pest and plant disease information, farm managers are unable to make proper decisions to prevent crop damage. This work aims to present how an integrated system was able to drive farm managers towards sustainable and data-driven IPM., Results: A system called Intelligent and Integrated Pest and Disease Management (I 2 PDM) system was developed. Edge computing devices were developed to automatically detect and recognize major greenhouse insect pests such as thrips (Frankliniella intonsa, Thrips hawaiiensis, and Thrips tabaci), and whiteflies (Bemisia argentifolii and Trialeurodes vaporariorum), to name a few, and measure environmental conditions including temperature, humidity, and light intensity, and send data to a remote server. The system has been installed in greenhouses producing tomatoes and orchids for gathering long-term spatiotemporal insect pest count and environmental data, for as long as 1368 days. The findings demonstrated that the proposed system supported the farm managers in performing IPM-related tasks. Significant yearly reductions in insect pest count as high as 50.7% were observed on the farms., Conclusion: It was concluded that novel and efficient strategies can be achieved by using an intelligent IPM system, opening IPM to potential benefits that cannot be easily realized with a traditional IPM program. This is the first work that reports the development of an intelligent strategic model for IPM based on actual automatically collected long-term data. The work presented herein can help in encouraging farm managers, researchers, experts, and industries to work together in implementing sustainable and data-driven IPM. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

In hospitals, safety climate refers to the safety policies and regulations established by medical institutions and the measures taken to ensure medical personnel feel safe while working at these institutions. Safety climate can directly affect the overall work performance of medical personnel and indirectly affect patient care quality, which in turn impacts the rate of occupational hazards. Common occupational hazards in the medical workplace include contracting infectious diseases, overwork, irregular circadian rhythm due to working shifts, changes in sleep patterns and dietary habits, musculoskeletal discomfort, workplace violence, workplace stress, and needlestick injuries. This paper was developed to explore the history of promoting needlestick prevention in Taiwan, and discusses how to use the results of empirical research as scientific evidence and critical proofs to advocate for needlestick prevention and to establish related policies. In addition, the process of how improvements to the hospital safety climate and the prevention of occupational hazard incidents mutually influence and complement each other was examined. Future studies are encouraged to explore this topic to further elucidate the sources of workplace stress and to devise methods to ameliorate their influence on workplace stress in medical institutions. The results of these studies may be referenced by relevant government agencies and medical institutions when developing policies promoting safe environments in hospitals that improve the safe-work perceptions of nursing personnel and create comfortable and friendly medical environments.

A 20-year-old girl came to the Tianjin Medical University Eye Hospital because of progressive herniation of her right eye for 3 months. Examination revealed a huge mass behind the right eyeball, which was clinically diagnosed as a space-occupying lesion of the right orbit. Because the tumor was close to the nerve, most of the tumor was resected and pathologically diagnosed as a poorly differentiated leiomyosarcoma. Orbital evisceration was performed later. There was no recurrence during the 10-year follow-up.

Aims: To find the incidence, risk factors and predictors of cardiovascular (CV) mortality for aortic stenosis (AS) in patients with type 2 diabetes mellitus (T2DM)., Methods: Between 2014 and 2019, 20,979 patients with T2DM who underwent echocardiography were enrolled for analysis. The mean follow-up period was 34 months. Multiple risk factors and outcomes for patients with and without AS were presented., Results: AS was present in 776 (3.70%) patients. Age, female, chronic kidney disease, hyperlipidemia, and peripheral arterial disease statistically increased risk of AS. The CV mortality (adjusted hazard ratio [aHR] = 1.97; 95% confidence interval [CI] 1.336 - 2.906, p < 0.001) and risk of hospitalization for heart failure (HHF) (aHR = 1.73, 95% CI 1.442-2.082, p < 0.001) were significantly increased in patients with AS, without significant differences in acute myocardial infarction and stroke. Severity of AS, body mass index (<27 kg/m 2 ), hypertension, hyperuricemia, left ventricular dysfunction (ejection fraction < 50%), and hematocrit (<38%) were significantly associated with increased CV mortality and HHF., Conclusions: AS was associated with an increased risk of CV mortality and HHF in patients with T2DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGF β activity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 blockade. Here we coupled the artificial intelligence (AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGF β pathway activity. Analysis of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution patterns. The digital image analysis approach achieves 74% concordance with the pathologist assessment for tumor-immune phenotypes. The transcriptomic profiling suggests that the TIL score was negatively correlated with TGF β pathway activation, together with elevated TGF β signaling activity observed in excluded and desert tumor phenotypes. The present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes: immune desert, immune excluded or immune inflamed. The association between "cold" tumor-immune phenotypes and TGF β signature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGF β blockade., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Increasing mitochondrial fusion by intra-tumoral grafting of membrane-fused mitochondria created with Pep-1 conjugation (P-Mito) contributes to breast cancer treatment, but it needs to be validated. Using mitochondrial division inhibitor-1 (Mdivi-1, Mdi) to disturb mitochondrial dynamics, we showed that the antitumor action of P-Mito in a mouse model of triple-negative breast cancer depends upon mitochondrial fusion and that Mdi treatment alone is ineffective. P-Mito significantly enhanced Doxorubicin (Dox) sensitivity by inducing mitochondrial fusion and mitophagy, and the same efficiency was also achieved with Mdi by inhibiting mitophagy. Cell death was induced via the p53 pathway and AIF nuclear translocation in the case of P-Mito, versus the caspase-dependent pathway for Mdi. Notably, both mitochondrial treatments reduced oxidative stress and blood vessel density of xenograft tumors, especially P-Mito, which was accompanied by inhibition of nuclear factor kappa-B activation. Furthermore, through enrichment analysis, four microRNAs in serum microvesicles induced by P-Mito caused expression of predicted targets via the PI3K-Akt pathway, and significantly impacted regulation of nuclear processes and myeloid cell differentiation. Clustering of gene-sets implicated a major steroid catabolic network. This study showed diverse roles of mitochondria in breast cancer and revealed effective adjuvant therapy targeting mitochondrial fusion and mitophagy., Competing Interests: Declaration of conflicting interests The authors have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In recent years, organic chromium (III) supplements have received increasing attentions for their low toxicity, high bioavailability and wide range of health-promoting benefits. This study aimed to investigate the preventive effects of chromium (III)-enriched yeast (YCr) on high-fat and high-fructose diet (HFHFD)-induced hyperlipidemia and hyperglycemia in mice, and further clarify its mechanism of action from the perspective of intestinal microbiomics and liver metabolomics. The results indicated that oral administration of YCr remarkably inhibited the aberrant elevations of body weight, blood glucose and lipid levels, hepatic cholesterol (TC) and triglyceride (TG) levels caused by HFHFD. Liver histological examination showed that oral YCr intervention inhibited HFHFD induced liver lipid accumulation. Besides, 16S rDNA amplicon sequencing showed that YCr intervention was beneficial to ameliorating intestinal microbiota dysbiosis by altering the proportion of some intestinal microbial phylotypes. Correlation-based network analysis indicated that the key intestinal microbial phylotypes intervened by YCr were closely related to some biochemical parameters associated with glucose and lipid metabolism. Liver metabolomics analysis revealed that dietary YCr intervention significantly regulated the levels of some biomarkers involved in purine metabolism, glycerophospholipid metabolism, citrate cycle, pyrimidine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and so on. Moreover, dietary YCr intervention regulated the mRNA levels of key genes associated with glucose, cholesterol, fatty acids and bile acids metabolism in liver. These findings suggest that dietary YCr intervention has beneficial effects on glucose and lipid metabolism by regulating intestinal microbiota and liver metabolic pathway, and thus can be served as a functional component to prevent hyperlipidemia and hyperglycemia., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Bipolar disorder (BD) is associated with cognitive impairment and mitochondrial dysfunction. However, the associations among mitochondrial DNA copy number (MCN), treatment response, and cognitive function remain elusive in BD patients., Methods: Sixty euthymic BD patients receiving valproate (VPA) and 66 healthy controls from the community were recruited. The indices of metabolic syndrome (MetS) were measured. Quantitative polymerase chain reaction analysis of blood leukocytes was used to measure the MCN. Cognitive function was measured by calculating perseverative errors and completed categories on the Wisconsin Card Sorting Test (WCST). The VPA treatment response was measured using the Alda scale., Results: BD patients had significantly higher MCN, triglyceride, and C-reactive protein (CRP) levels, waist circumference, and worse performance on the WCST than the controls. Regression models showed that BD itself and the VPA concentration exerted significant effects on increased MCN levels. Moreover, the receiver operating characteristic curve analysis showed that an MCN of 2.05 distinguished VPA responders from nonresponders, with an area under the curve of 0.705 and a sensitivity and specificity of 0.529 and 0.816, respectively. An MCN level ≥2.05 was associated with 5.39 higher odds of being a VPA responder (P = .006). BD patients who were stratified into the high-MCN group had a higher VPA response rate, better WCST performance, lower CRP level, and less MetS., Conclusions: The study suggests a link between the peripheral MCN and cognitive function in BD patients. As an inflammatory status, MetS might modulate this association., (© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.)

Background: The predictive values of the platelet to lymphocyte ratio (PLR) and red cell distribution width (RDW) have been demonstrated in different types of abdominal surgery. The aim of this study was to investigate the interest of the preoperative PLR and RDW as predictors of 30-day postoperative complications in patients with acute mesenteric ischemia (AMI)., Methods: Clinical data of 105 AMI patients were retrospectively reviewed. Postoperative complications were evaluated by the Clavien-Dindo classification. The cutoff values for neutrophil to lymphocyte ratio (NLR), PLR, and RDW were determined by receiver operating characteristic curves. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed., Results: In the univariate analyses, advanced age, female, anemia, high white blood cell (WBC), high PLR, high NLR, high RDW, Charlson comorbidity index (CCI) score ≥2, and bowel resection were associated with the postoperative complications. A multivariable analysis revealed that advanced age, high PLR, high RDW, and bowel resection were independent predictors of postoperative complications., Conclusions: The PLR and RDW might play important roles in evaluation of the risk of postoperative complications in AMI patients. The preoperative PLR and RDW are simple and useful predictors of postoperative complications in AMI patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Some evidence suggests that male infertility increases the risk of cardiovascular diseases (CVDs). However, the evidence in Asian populations is relatively scarce. The aim of this study is to determine whether male infertility increases the risk of CVDs., Materials and Methods: We used inpatient and outpatient data for the years 2000 to 2015 from the Taiwanese Longitudinal Health Insurance Database. We enrolled 7,016 males over 18 years old and diagnosed with male infertility. Of these, 2,326 matched our inclusion criteria and were assigned to the study group. For each infertility patient, four comparison patients were frequency-matched by age and index date to form a control cohort comprising 9,304 patients. Cox proportional hazards analysis was used to estimate the association between male infertility and CVDs., Results: After a 15-year follow-up, the incidence rate of CVDs was higher in the infertility group than the control group (1,460.23 and 1,073.70 per 100,000 person-years, respectively). The Cox proportional hazards regression analysis revealed that the adjusted HR for CVDs was 1.472 for the infertility group (95% CI, 1.288-1.683; p<0.001) relative to the control group. The Kaplan-Meier analysis of the cumulative incidence of CVDs in the two groups showed that the cumulative risk curve for CVDs was significantly higher for the infertility group than the control group., Conclusions: This study shows that men with infertility have a higher risk of developing incident CVDs. In the future, healthcare providers should pay attention to these patients because of their higher health risks., Competing Interests: The authors have nothing to disclose., (Copyright © 2022 Korean Society for Sexual Medicine and Andrology.)

Rationale and Objectives: To investigate the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and texture parameters of primary lesions and lymph nodes for predicting pelvic lymph node metastasis in patients with cervical cancer., Materials and Methods: A total of 143 patients with cervical cancer confirmed by surgical pathology were analyzed retrospectively and 125 patients were enrolled in primary lesions study, 83 patients and 134 lymph nodes were enrolled in lymph nodes study. Patients and lymph nodes were randomly divided into training group and test group at a ratio of 2: 1. The IVIM-DWI parameters and 3D texture features of primary lesions and lymph nodes of all patients were measured. The least absolute shrinkage and selection operator algorithm, spearman's correlation analysis, independent two-sample t-test and Mann-Whitney U-test were used to select texture parameters. Multivariate Logistic regression analysis and receiver operating characteristic curves were used to model and evaluate diagnostic performances., Results: In primary lesions study, model 1 was constructed by combining f value, original&#95;shape&#95;Sphericity and original&#95;firstorder&#95;Mean of primary lesions. In lymph nodes study, model 2 was constructed by combining short diameter, circular enhancement and rough margin of lymph nodes. Model 3 was constructed by combining ADC, f value and original&#95;glszm&#95;Small Area Emphasis of lymph nodes. The areas under curve of model 1, 2 and 3 in training group and test group were 0.882, 0.798, 0.907 and 0.862, 0.771, 0.937 respectively., Conclusion: Models based on IVIM-DWI and texture parameters of primary lesions and lymph nodes both performed well in diagnosing pelvic lymph node metastasis of cervical cancer and were superior to morphological features of lymph nodes. Especially, parameters of lymph nodes showed higher diagnostic efficiency and clinical significance., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Wearable devices have been found effective in training ankle control in patients with neurological diseases. However, the neural mechanisms associated with using wearable devices for ankle training remain largely unexplored. This study aimed to investigate the ankle tracking performance and brain white matter changes associated with ankle tracking learning using a wearable-device system and the behavior-brain structure relationships in middle-aged and older adults., Methods: Twenty-six middle-aged and older adults (48-75 years) participated in this study. Participants underwent 5-day ankle tracking learning with their non-dominant foot using a custom-built ankle tracking system equipped with a wearable sensor and a sensor-computer interface for real-time visual feedback and data acquisition. Repeated and random sequences of target tracking trajectories were both used for learning and testing. Ankle tracking performance, calculated as the root-mean-squared-error (RMSE) between the target and actual ankle trajectories, and brain diffusion spectrum MR images were acquired at baseline and retention tests. The general fractional anisotropy (GFA) values of eight brain white matter tracts of interest were calculated to indicate their integrity. Two-way (Sex × Time) mixed repeated measures ANOVA procedures were used to investigate Sex and Time effects on RMSE and GFA. Correlations between changes in RMSE and those in GFA were analyzed, controlling for age and sex., Results: After learning, both male and female participants reduced the RMSE of tracking repeated and random sequences (both p < 0.001). Among the eight fiber tracts, the right superior longitudinal fasciculus II (R SLF II) was the only one which showed both increased GFA (p = 0.039) after learning and predictive power of reductions in RMSE for random sequence tracking with its changes in GFA [β = 0.514, R 2 change = 0.259, p = 0.008]., Conclusions: Our findings implied that interactive tracking movement learning using wearable sensors may place high demands on the attention, sensory feedback integration, and sensorimotor transformation functions of the brain. Therefore, the SLF II, which is known to perform these brain functions, showed corresponding neural plasticity after such learning, and its plasticity also predicted the behavioral gains. The SLF II appears to be a very important anatomical neural correlate involved in such learning paradigms., (© 2022. The Author(s).)

Purpose: There is a significant disparity in global cancer care and outcome between countries. Progress in the treatment of symptomatic plasma cell myeloma (PCM) in high-income countries is not seen in low- and middle-income countries., Materials and Methods: This is was a retrospective cohort study of all patients diagnosed with PCM between May 1, 2013, and September 30, 2021, at the first hemato-oncology center in Sri Lanka. We aimed to provide data on clinicopathologic characteristics, response, and survival estimates., Results: A total of 79 patients with PCM received first-line therapy during the study period. The median age was 64 years, and approximately one third (33%) of patients were older than 70 years. There were 42 (53%) males and 37 females. Hypercalcemia, renal impairment, anemia, and bone disease were detected in 36.7%, 38%, 72.1%, and 81%, respectively. Thirty-nine, 34, and six patients received a combination of cyclophosphamide, thalidomide, and dexamethasone; bortezomib, thalidomide, and dexamethasone; and other treatments, respectively. The overall response rate (≥ partial response) was approximately 97% for both cyclophosphamide, thalidomide, and dexamethasone and bortezomib, thalidomide, and dexamethasone. Twenty-three (29%) of these patients died during the study period, but only 14 (18%) died due to PCM or associated sepsis. After a median follow-up of 40.6 months (range, 35.2-59.07 months), the median overall survival was 84.2 months (95% CI, 60.87 to not available). The 5-year estimated overall survival was 65%., Conclusion: To our knowledge, this is the only well-characterized study on long-term survival of patients with PCM in Sri Lanka. We have shown that it is possible to successfully apply Western treatment and supportive care protocols to the local population. These published data will help to benchmark and improve the treatment and develop blood cancer care in the local setting.

Objectives: To study the clinical effect and adverse drug reactions of different doses of glucocorticoid (GC) in the treatment of children with recurrence of steroid-sensitive nephrotic syndrome (SSNS)., Methods: A total of 67 children who were hospitalized and diagnosed with SSNS recurrence in the Department of Nephrology, Children's Hospital, Capital Institute of Pediatrics, from November 2017 to December 2019 were enrolled. They were randomly divided into a moderate-dose GC group (32 children) and a full-dose GC group (35 children). The two groups were compared in terms of urinary protein clearance, recurrence rate within 6 months, and incidence rate of GC-associated adverse reactions., Results: There was no significant difference in the urinary protein clearance rate between the moderate-dose GC and full-dose GC groups (91% vs 94%, P >0.05). There was also no significant difference in the recurrence rate within 6 months between the two groups (41% vs 36%, P >0.05). At 6 months of follow-up, compared with the full-dose GC group, the moderate-dose GC group had a significantly lower cumulative dose of prednisone [(87±18) mg/kg vs (98±16) mg/kg, P =0.039] and a significantly lower proportion of children with an abnormal increase in body weight (6% vs 33%, P =0.045). The logistic regression analysis showed that prednisone dose ≥10 mg/alternate day at enrollment was a risk factor for recurrence within 6 months in children with SSNS ( P =0.018)., Conclusions: For children with SSNS recurrence, moderate-dose GC has similar effects to full-dose GC in the remission induction rate and the recurrence rate within 6 months, with a lower cumulative dose and fewer GC-associated adverse reactions within 6 months than full-dose GC.

Chlorophyll (Chl) plays a crucial role in plant photosynthesis. The geranylgeraniol reductase gene ( CHLP ) participates in the terminal hydrogenation of chlorophyll biosynthesis. Although there are many studies related to the genome-wide analysis of Populus trichocarpa , little research has been conducted on CHLP family genes, especially those concerning growth and photosynthesis. In this study, three CHLP genes were identified in Populus . The evolutionary tree indicated that the CHLP family genes were divided into six groups. Moreover, one pair of genes was derived from segmental duplications in Populus . Many elements related to growth were detected by cis -acting element analysis of the promoters of diverse PtrCHLPs . Furthermore, PtrCHLPs exhibit different tissue expression patterns. In addition, PtrCHLP3 is preferentially expressed in the leaves and plays an important role in regulating chlorophyll biosynthesis. Silencing of PtrCHLP3 in poplar resulted in a decrease in chlorophyll synthesis in plants, thus blocking electron transport during photosynthesis. Furthermore, inhibition of PtrCHLP3 expression in poplar can inhibit plant growth through the downregulation of photosynthesis. Ultimately, PtrCHLP3 formed a co-expression network with photosynthesis and chlorophyll biosynthesis-related genes, which synergistically affected the growth and photosynthesis of poplars. Thus, this study provides genetic resources for the improved breeding of fast-growing tree traits., 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 He, Shi, Chen, Li, Niu, Feng, Lu, Tian, Zhang, Lin, Chen, Liu and Wan.)

Objective: Low muscle mass and quality is associated with poor surgical outcomes. Psoas muscle density (PMD)is a validated surrogate for muscle quality that can be easily measured from a clinical computed tomography (CT) scan. The objective of this study was to investigate the association between PMD and short-term postoperative outcomes in patients with acute mesenteric ischemia (AMI)., Methods: From April 2006 and September 2019, the clinical data of all patients who underwent surgical intervention with a preoperative diagnosis of AMI and had preoperative non-contrast CT images available were retrospectively reviewed. PMD was measured by CT at the third lumbar vertebra. The lowest quartile of PMD for men and women in all patients was used as sex-specific cut-off values for low PMD. Univariate and multivariate analyses evaluating risk factors of postoperative complications and 30-day mortality were performed., Results: The cohort consisted of 88 patients with a mean age of 58.8 ± 16.2 years, of whom 21 (23.9%) patients had low PMD based on the diagnostic cut-off values (40.5 HU for men and 28.4 HU for women), 35 (39.8%) patients developed complications within 30 days of the operation, and 10 (11.3%) patients died within 30 days of surgery. Low PMD patients had a higher risk of postoperative complications and 30-day mortality than patients without low PMD patients. In a multivariate analysis, low PMD and low psoas muscle area (PMA) were independent predictors of postoperative complications. However, only low PMD remained an independent risk factor for 30-day mortality., Conclusions: Preoperative assessment of the PMD on CT can be a practical method for identifying AMI patients at risk for postoperative complications and 30-day mortality., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Cadmium, a toxic heavy metal, seriously affects human health and ecological security. The cation/H + exchanger (CAX) family is a unique metal transporter that plays a crucial role in Cd acquisition, transfer, and remission in plants. Although there are many studies related to the genome-wide analysis of Populus trichocarpa, little research has been done on the CAX family genes, especially concerning Cd stress. In this study, genome-wide analysis of the Populus CAX family identified seven stress-related CAX genes. The evolutionary tree indicated that the CaCA family genes were grouped into four clusters. Moreover, seven pairs of genes were derived by segmental duplication in poplars. Cis-acting element analysis identified numerous stress-related elements in the promoters of diverse PtrCAXs. Furthermore, some PtrCAXs were up-regulated by drought, beetle, and mechanical damage, indicating their possible function in regulating stress response. Under cadmium stress, all CAX genes in the roots were up-regulated. Our findings suggest that plants may regulate their response to Cd stress through the TF-CAXs module. Comprehensively investigating the CAX family provides a scientific basis for the phytoremediation of heavy metal pollution by Populus., (Copyright © 2022. Published by Elsevier B.V.)