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Objectives: This study aimed to primarily examine the association between memory deficit and increased fall risk, second, explore the underlying neuroanatomical linkage of this association in the elderly with aMCI and mild AD. Methods: In this cross-sectional study, a total of 103 older adults were included (55 cognitively normal, CN; 48 cognitive impairment, CI, elderly with aMCI, and mild AD). Memory was assessed by the Auditory Verbal Learning Test (AVLT). Fall risk was evaluated by the Timed Up and Go (TUG) Test, heel strike angles, and stride speed, which were collected by an inertial-sensor-based wearable instrument (the JiBuEn™ gait analysis system). Brain volumes were full-automatic segmented and quantified using AccuBrain® v1.2 from three-dimensional T1-weighted (3D T1W) MR images. Multivariable regression analysis was used to examine the extent of the association between memory deficit and fall risk, the association of brain volumes with memory, and fall risk. Age, sex, education, BMI, and HAMD scores were adjusted. Sensitivity analysis was conducted. Results: Compared to CN, participants with aMCI and mild AD had poorer cognitive performance (p < 0.001), longer TUG time (p = 0.018), and smaller hippocampus and medial temporal volumes (p = 0.037 and 0.029). In the CI group, compared to good short delayed memory (SDM) performance (AVLT > 5), the elderly with bad SDM performance (AVLT ≤ 3) had longer TUG time, smaller heel strike angles, and slower stride speed. Multivariable regression analysis showed that elderly with poor memory had higher fall risk than relative good memory performance among cognitive impairment elderly. The TUG time increased by 2.1 s, 95% CI, 0.54∼3.67; left heel strike angle reduced by 3.22°, 95% CI, −6.05 to −0.39; and stride speed reduced by 0.09 m/s, 95% CI, −0.19 to −0.00 for the poor memory elderly among the CI group, but not found the association in CN group. In addition, serious medial temporal atrophy (MTA), small volumes of the frontal lobe and occipital lobe were associated with long TUG time and small heel strike angles; small volumes of the temporal lobe, frontal lobe, and parietal lobe were associated with slow stride speed. Conclusion: Our findings suggested that memory deficit was associated with increased fall risk in the elderly with aMCI and mild AD. The association might be mediated by the atrophy of medial temporal, frontal, and parietal lobes. Additionally, increased fall risk, tested by TUG time, heel stride angles, and stride speed, might be objective and convenient kinematics markers for dynamic monitoring of both memory function and fall risk. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer with limited treatment options and extremely poor prognosis worldwide. Recently, the proteolysis targeting chimeras (PROTACs), which aim to induce proteasome-mediated degradation of interesting proteins via recruiting E3 ligases, have become the advanced tools and attractive molecules for cancer treatment. However, the anticancer effects of PROTACs in HCC remain to be clarified. Here, we evaluate the anticancer activity of ARV-771, a previously reported PROTAC compound designed for bromodomain and extra-terminal domain (BET) proteins, in HCC. We show that ARV-771 suppresses the cell viability and colony formation of HCC cells via arresting cell cycle progression and triggering apoptosis. Further investigations reveal that ARV-771 notably downregulates multiple non-proteasomal deubiquitinases which are critical to the development of cancers. Additionally, HCC cells can decrease their sensitivity to ARV-771 via activating the MEK/ERK and p38 MAPKs. ARV-771 also inhibits HCC progression in vivo. Moreover, we show that ARV-771 and sorafenib, a Raf inhibitor that clinically used for targeted therapy of liver cancer, can synergistically inhibit the growth of HCC cells. Overall, this study not only explores the anticancer activity of ARV-771 and its underlying mechanisms in HCC, but also deepens our understanding of deubiquitinases, MAPKs, cell cycle, and apoptosis induction in cancer therapy. [ABSTRACT FROM AUTHOR]

Study objectives: To investigate the extent to which sleep quality associated with plasma Aβ levels in amnestic mild cognitive impairment (aMCI) elderly. Methods: A total of 172 cognitively normal (NC) elderly and 133 aMCI elderly were included in this study. For the evaluation of sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used. Levels of plasma Aβ were determined by the sandwich enzyme-linked immunosorbent assay technique. Multivariable linear regression analysis was applied to evaluate associations between sleep quality and plasma Aβ levels after adjusting potential confounders. Results: Compared to NC subjects, participants with aMCI had a higher global PSQI score (8.72 ± 3.87 vs. 7.10 ± 3.07, p < 0.001). The global PSQI score was positively associated with plasma Aβ42 level in the aMCI group (β = 0.063, 95% CI 0.001–0.125, and p = 0.049) but not in the NC group (p > 0.05). Additionally, a higher global PSQI score was associated with a higher plasma Aβ42/Aβ40 ratio in both NC (β = 0.010, 95% CI 0.003–0.016, and p = 0.003) and aMCI groups (β = 0.012, 95% CI 0.005–0.018, and p < 0.001). The association between global PSQI score and plasma Aβ42/Aβ40 ratio was stronger in individuals with aMCI relative to the NC subjects (β = 0.076 vs. 0.030, p for interaction = 0.023). Conclusion: Poor sleep quality was associated with plasma Aβ42 and Aβ42/Aβ40 ratio, with a stronger effect among individuals with aMCI. A better understanding of the role of sleep in plasma Aβ levels in aMCI patients could lead to effective sleep-based intervention against the risk of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Forensic entomology could provide valuable data for the minimum postmortem interval (PMImin) estimation and other relevant information, such as causes and circumstances of death. Some representatives of flesh flies are one of the dominant necrophagous insects during early stages of decomposition, demonstrating unique biological characteristics compared with other necrophagous flies. Moreover, they lead to global health concerns as carriers of various pathogenic micro-organisms, and dominantly result in the traumatic myiasis. Thus, sarcophagid flies are considered important in decomposition processes for PMImin estimation. However, the utility of sarcophagid flies has been seriously hampered by limited ecological, biological and taxonomic knowledge of them. The aim of this paper is to provide a brief review on the species, distribution and biological habit of forensically important sarcophagid flies. In addition, the relation between traumatic myiasis and flesh flies, molecular identification methods and developmental pattern of flesh flies are summarized. [ABSTRACT FROM AUTHOR]

Subjective well-being includes ‘affect’ and ‘satisfaction with life’ (SWL). This study proposes a unified approach to construct a profile of subjective well-being based on social media language in Facebook status updates. We apply sentiment analysis to generate users’ affect scores, and train a random forest model to predict SWL using affect scores and other language features of the status updates. Results show that: the computer-selected features resemble the key predictors of SWL as identified in early studies; the machine-predicted SWL is moderately correlated with the self-reported SWL (r = 0.36, p < 0.01), indicating that language-based assessment can constitute valid SWL measures; the machine-assessed affect scores resemble those reported in a previous experimental study; and the machine-predicted subjective well-being profile can also reflect other psychological traits like depression (r = 0.24, p < 0.01). This study provides important insights for psychological prediction using multiple, machine-assessed components and longitudinal or dense psychological assessment using social media language. [ABSTRACT FROM AUTHOR]

To describe the combined surgical technique of laparoscopic radical hysterectomy and pelvic lymphadenectomy (LRH + LPL) for cervical cancers and summarize our experiences in prevention and treatment of complications, so as to provide strategies to prevent and appropriately manage the complications that may occur during these procedures.A retrospective study was conducted on LRH + LPL in 117 cases of cervical cancer with International Federation of Gynecology and Obstetrics stages Ib (n = 96) and II a (n = 21) from August 1998 to December 2006. The intraoperative and postoperative complications were analyzed.The overall conversion rate was 1.7% (2/117). Four patients had vessel injuries, 3 of which were treated laparoscopically. One patient had a common iliac vein laceration that could not be controlled laparoscopically after failing to deal with the injured branch of common iliac vein. Cystotomy occurred in 5 patients. One case of stage IIa with a bladder laceration longer than 3 cm was converted to laparotomy during the early stages of the learning curve. The remaining 4 were managed laparoscopically. Postoperative complications occurred in 38.5% (n = 45) of the patients, including 38 patients with urinary retention who exhibited complete resolution within 6 months by intermittent training and catheterization, 4 with lymphocyst who underwent conservation treatment, 1 with ureteral fistula that was treated by cystoscopic placement of double-J ureteral stents, 1 with mild adynamic bowel obstruction who received conservative management, and 1 with vesicovaginal fistula that was closed by conservative treatment.With the continuous skilled laparoscopic technology, mastering the tips of prevention, and treatment of complications, LRH + LPL will be widely performed in the future. [ABSTRACT FROM AUTHOR]

Abstract: Objective. : To compare the feasibility, morbidity, and survival outcome of the laparoscopic radical hysterectomy and pelvic lymphadenectomy (LRH+LPL) with abdominal radical hysterectomy and pelvic lymphadenectomy (ARH+APL) for FIGO stage Ib-IIa cervical carcinoma. Methods. : The consecutive cases with FIGO Ib-IIa cervical cancer from August 1998 to December 2005 were documented, including 90 patients underwent LRH+LPL, and 35 patients underwent ARH+APL as control group. The clinic data of perioperative periods and survival were compared between groups. Results. : In laparoscopy group the operating time increased significantly (262.99±67.6 min vs. 217.2±71.56 min, P =0.001), and the recovery time of bowel decreased significantly (1.96±0.62 days vs. 2.40±1.06 days, P =0.025). No significant difference was found between groups when the blood loss during operation (369.78±249.94 ml vs. 455.14±338.05 ml, P =0.125), numbers of the pelvic lymph nodes resected (21.28±8.39 vs. 18.77±9.47, P =0.151), recovery time of bladder function and postoperative hospital stays were compared. All laparoscopic procedures were completed successfully except 2 cases converted to laparotomy. The median follow-up was 26 months (range 5 to 84 months). Ten and five cases lost to follow-up in laparoscopy and laparotomy group, respectively. Excluding the lost cases, the recurrence rate (13.75% vs. 12%, P >0.05) and the mortality rate (10% vs. 8%, P >0.05) between groups was similar. Conclusion. : Our data demonstrated that cervical cancer could be treated successfully with LRH+LPL with similar efficacy and recurrence rates to ARH+APL. LRH+LPL is a safe and effective alternative to conventional abdominal surgery for stage Ib-IIa cervical cancer, and should be used if the surgeon is sufficiently trained. Its clinical value should be confirmed by multicenter randomized clinic trials. [Copyright &y& Elsevier]

Introduction. Hypertension is the most prevalent chronic disease and a major risk factor for cardiovascular and cerebrovascular diseases. Gap statement. However, there has been no substantial breakthrough in aetiology, new drug targets, and drug development of hypertension in recent 50 years. Research aim. Therefore, this study was to screen unique intestinal microbiome and serum metabolic biomarkers which can early diagnose and track the prognosis of hypertension patients in different periods, and analyse its underlying mechanisms and functions. Methods. Four groups of stool and serum samples, including healthy controls (HCs), prehypertension (PHT), hypertension (HT), and hypertension-related complications (HTC), were collected. Microbial diversity assessed using 16S rRNA sequencing. The metabolites in serum samples were detected through LC-MS/MS analysis. Results. The composition of gut microbiota in patients exhibited dissimilarities compared to that in healthy subjects, which was distinguished by Prevotella, Slackia , Enterococcus , Bifidobacterium, and Lactobacillales may be potential markers for tracking the progression of hypertension, and Bifidobacterium , Butyricimonas , Adlercreutzia , Faecalibacterium , Lactobacillus , Ruminococcus , Clostridium , and Acidaminococcus demonstrated diagnostic value. Meanwhile, tracking the dynamic changes of deoxycholic acid, 4-oxododecanedioic acid, and l-arginine can serve as biomarkers for early diagnosis, and investigation into the mechanism by which the intestinal microbiome influences the onset and progression of hypertension. In terms of pathogenesis, the findings revealed that Bifidobacterium may caused the changes of AST, indirect bilirubin, ALT, triglyceride and uric acid by affecting metabolites cis-7-hexadecenoic acid methyl ester and N1-acetylspermidine. Additionally, Coprococcus may cause changes in albumin through the influence of androsterone enanthate. Conclusions. These findings highlight that the unique intestinal microbiome and serum metabolic profile in different periods of hypertension will provide valuable insight for timely diagnosis and prognosis tracking in hypertension patients with promising clinical applications.

Objective: This study aimed to develop a diagnostic model of multi-kinematic parameters for patients with amnestic mild cognitive impairment (aMCI)., Method: In this cross-sectional study, 94 older adults were included (33 cognitively normal, CN; and 61 aMCI). We conducted neuropsychological battery tests, such as global cognition and cognitive domains, and collected gait parameters by an inertial-sensor gait analysis system. Multivariable regression models were used to identify the potential diagnostic variables for aMCI. Receiver operating characteristic (ROC) curves were applied to assess the diagnostic accuracy of kinematic parameters in discriminating aMCI from healthy subjects., Results: Multivariable regression showed that multi-kinematic parameters were the potential diagnostic variables for aMCI. The multi-kinematic parameter model, developed using Timed Up and Go (TUG) time, stride length, toe-off/heel stride angles, one-leg standing (OLS) time, and braking force, showed areas under ROC (AUC), 0.96 [95% confidence interval (CI), 0.905-0.857]; sensitivity, 0.90; and specificity, 0.91. In contrast, a single kinematic parameter's sensitivity was 0.26-0.95 and specificity was 0.21-0.90. Notably, the separating capacity of multi-kinematic parameters was highly similar to Montreal Cognitive Assessment (MoCA; AUC: 0.96 vs. 0.95). Compared to cognitive domain tests, the separating ability was comparable to Auditory Verbal Learning Test (AVLT) and Boston Naming Test (BNT; AUC: 0.96 vs. 0.97; AUC: 0.96 vs. 0.94)., Conclusion: We developed one diagnostic model of multi-kinematic parameters for patients with aMCI in Foshan., 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 Huang, Hou, Liu, Shang, Luo, Lv, Zhang, Lin, Huang, Tao, Wang, Zhang, Chen, Pan and Xie.)

Background: The present study aimed to investigate longitudinal associations between bone mineral densities (BMDs) and appendicular skeletal muscle (ASM) mass in different regions of the body using three different indicators, in Chinese community-dwelling middle-aged and elderly men., Methods: A total of 1,343 men aged ≥ 40 years from a Chinese community were assessed at baseline (2014-2016), one-year follow-up (2016-2017; n  = 648), two-year follow-up (2017-2018; n  = 407), and three-year follow up (2018-2019; n  = 208). At all the four time-points, measurements included ASM mass and BMDs for all regions of the body using dual-energy X-ray absorptiometry. A questionnaire was completed by patients and biochemical markers were assessed. We applied three different indicators to define ASM mass or lean mass respectively, including the appendicular skeletal muscle index (ASM adjusted by height, ASMI, according to the Asian Working Group for Sarcopenia), skeletal muscle index (ASM adjusted by weight, SMI, according to the International Working Group on Sarcopenia), and the appendicular skeletal muscle/body mass index (ratio of ASM and Body mass index (BMI), ASM/BMI, according to the Foundation for the National Institutes of Health). After adjusting for potential confounders, the generalized additive mixed model (GAMM) was used to analyze the trend in ASM mass over time, and to test the association between ASM mass and regional and whole-body BMDs., Results: The incidence of low lean mass was 8.2% defined by ASMI, 16.3% defined by SMI, and 8.3% defined by ASM/BMI. There was a linear relationship between BMDs and ASM mass, and ASMI, ASM/BMI, and SMI gradually decreased with time. After adjusting for covariances, GAMM analysis determined longitudinal associations between BMDs and ASM mass by three indicators respectively: the skull BMD was negatively associated with ASM mass. For each unit increase in skull BMD, ASMI decreased by 0.28 kg/m 2 (95% confidence interval (CI) [-0.39 to -0.16]), ASM/BMI decreased by 0.02 m 2 (95% CI [-0.03 to -0.00]), and SMI decreased by 0.01% (95% CI[-0.01 to -0.00]). The remaining parameters (including whole-body mean BMD, thoracic spinal BMD, lumbar spinal BMD, hip BMD, femoral neck BMD, pelvic BMD, left arm BMD, right arm BMD, left leg BMD, right leg BMD) were positively correlated with ASM mass. The ASMI increased by 3.07 kg/m 2 for each unit increase in the femoral neck BMD (95% CI [2.31-3.84]). The ASM/BMI increased by 0.22 m 2 for each unit increase in the left arm BMD (95% CI [0.12-0.33]), and the SMI increased by 0.05% per unit increase in the left arm BMD (95% CI [0.02-0.08])., Conclusions: Compared to ASMI and ASM/BMI, SMI was more sensitive to screen for the low lean mass. Skull BMD was negatively associated with ASM mass, while BMDs throughout the rest of the body were positively correlated with ASM mass among the middle-aged and elderly Chinese men., Competing Interests: The authors declare there are no competing interests., (©2021 Xu et al.)

Catecholamine metabolism plays an important role in the determination of insect body color and cuticle sclerotization. To date, limited research has focused on these processes in silkworm. In the current study, we analyzed the interactions between catecholamines and melanin genes and their effects on the pigmentation patterns and physical properties of sclerotized regions in silkworm, using the melanic mutant melanism (mln) silkworm strain as a model. Injection of β-alanine into mln mutant silkworm induced a change in catecholamine metabolism and turned its body color yellow. Further investigation of the catecholamine content and expression levels of the corresponding melanin genes from different developmental stages of Dazao-mln (mutant) and Dazao (wild-type) silkworm revealed that at the larval and adult stages, the expression patterns of melanin genes precipitated dopamine accumulation corresponding to functional loss of Bm-iAANAT, a repressive effect of excess NBAD on ebony, and upregulation of tan in the Dazao-mln strain. During the early pupal stage, dopamine did not accumulate in Dazao-mln, since upregulation of ebony and black genes led to conversion of high amounts of dopamine into NBAD, resulting in deep yellow cuticles. Scanning electron microscope analysis of a cross-section of adult dorsal plates from both wild-type and mutant silkworm disclosed the formation of different layers in Dazao-mln owing to lack of NADA, compared to even and dense layers in Dazao. Analysis of the mechanical properties of the anterior wings revealed higher storage modulus and lower loss tangent in Dazao-mln, which was closely associated with the altered catecholamine metabolism in the mutant strain. Based on these findings, we conclude that catecholamine metabolism is crucial for the color pattern and physical properties of cuticles in silkworm. Our results should provide a significant contribution to Lepidoptera cuticle tanning research.