Miracle-dz/UniFAR-FTUs huggingface dataset:
Xanthohumol ameliorates memory impairment and reduces the deposition of β-amyloid in APP/PS1 mice via regulating the mTOR/LC3II and Bax/Bcl-2 signalling pathways.

OBJECTIVES Xanthohumol (XAN) is a unique component of Humulus lupulus L. and is known for its diverse biological activities. In this study, we investigated whether Xanthohumol could ameliorate memory impairment of APP/PS1 mice, and explored its potential mechanism of action. METHODS APP/PS1 mice were used for in vivo test and were treated with N-acetylcysteine and Xanthohumol for 2 months. Learning and memory levels were evaluated by the Morris water maze. Inflammatory and oxidative markers in serum and hippocampus and the deposition of Aβ in the hippocampus were determined. Moreover, the expression of autophagy and apoptosis proteins was also evaluated by western blot. KEY FINDINGS Xanthohumol significantly reduced the latency and increased the residence time of mice in the target quadrant. Additionally, Xanthohumol increased superoxide dismutase level and reduced Interleukin-6 and Interleukin-1β levels both in serum and hippocampus. Xanthohumol also significantly reduced Aβ deposition in the hippocampus and activated autophagy and anti-apoptotic signals. CONCLUSIONS Xanthohumol effectively ameliorates memory impairment of APP/PS1 mice by activating mTOR/LC3 and Bax/Bcl-2 signalling pathways, which provides new insight into the neuroprotective effects of Xanthohumol.
The reliability and validity of the compulsory citizenship behaviors (CCBs) scale: Six-step R-based psychometrics protocol among nurses in Turkey.

PURPOSE This study aims to assess the validity and reliability of the compulsory citizenship behaviors (CCBs) scale among Turkish nurses. METHODS The sample of this cross-sectional study consisted of 530 Turkish hospital nurses. We performed a six-step protocol to test the validity of the scale. FINDINGS The scale formed a unidimensional scale with good homogeneity (H = 0.79) and reliability (α = 0.94). The confirmatory factor analysis indicated that the five-item single factor measurement model of the scale well fit the data (GFI = 0.98, CFI = 0.99, TLI = 0.98, SRMR = 0.02, RMSEA = 0.10). PRACTICAL IMPLICATIONS The Turkish version of the CCBs scale satisfactorily met psychometric criteria in Turkish nurse samples and is recommended for further research.
CRISPR Genome Editing Made Easy Through the CHOPCHOP Website

The design of optimal guide RNA (gRNA) sequences for CRISPR systems is challenged by the need to achieve highly efficient editing at the desired location (on‐target editing) with minimal editing at unintended locations (off‐target editing). Although laboratory validation should ideally be used to detect off‐target activity, computational predictions are almost always preferred in practice due to their speed and low cost. Several studies have therefore explored gRNA‐DNA interactions in order to understand how CRISPR complexes select their genomic targets. CHOPCHOP (https://chopchop.cbu.uib.no/) leverages these developments to build a user‐friendly web interface that helps users design optimal gRNAs. CHOPCHOP supports a wide range of CRISPR applications, including gene knock‐out, sequence knock‐in, and RNA knock‐down. Furthermore, CHOPCHOP offers visualization that enables an informed choice of gRNAs and supports experimental validation. In these protocols, we describe the best practices for gRNA design using CHOPCHOP. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.
Atomically thin semiconducting layers and nanomembranes: a review

This article reviews the main physical properties of atomically thin semiconductors and the electronic devices based on them. We start with graphene, describing its physical properties and growth methods, followed by a discussion of its electronic device applications. Then, transition metal dichalcogenides (TMDs) are analyzed as a prototype of atomically thin semiconductors, their physical properties, growth methods, and electronic devices are discussed in detail. Finally, non-layered semiconducting membranes with thicknesses ranging from a few nanometers to about 50 nm, and considered as counterparts of atomically thin semiconductors, are analyzed, and their applications presented.
Association Between Gender-Affirming Surgeries and Mental Health Outcomes.

Importance Requests for gender-affirming surgeries are rapidly increasing among transgender and gender diverse (TGD) people. However, there is limited evidence regarding the mental health benefits of these surgeries. Objective To evaluate associations between gender-affirming surgeries and mental health outcomes, including psychological distress, substance use, and suicide risk. Design, Setting, and Participants In this study, we performed a secondary analysis of data from the 2015 US Transgender Survey, the largest existing data set containing comprehensive information on the surgical and mental health experiences of TGD people. The survey was conducted across 50 states, Washington, DC, US territories, and US military bases abroad. A total of 27 715 TGD adults took the US Transgender Survey, which was disseminated by community-based outreach from August 19, 2015, to September 21, 2015. Data were analyzed between November 1, 2020, and January 3, 2021. Exposures The exposure group included respondents who endorsed undergoing 1 or more types of gender-affirming surgery at least 2 years prior to submitting survey responses. The comparison group included respondents who endorsed a desire for 1 or more types of gender-affirming surgery but denied undergoing any gender-affirming surgeries. Main Outcomes and Measures Endorsement of past-month severe psychological distress (score of ≥13 on Kessler Psychological Distress Scale), past-month binge alcohol use, past-year tobacco smoking, and past-year suicidal ideation or suicide attempt. Results Of the 27 715 respondents, 3559 (12.8%) endorsed undergoing 1 or more types of gender-affirming surgery at least 2 years prior to submitting survey responses, while 16 401 (59.2%) endorsed a desire to undergo 1 or more types of gender-affirming surgery but denied undergoing any of these. Of the respondents in this study sample, 16 182 (81.1%) were between the ages of 18 and 44 years, 16 386 (82.1%) identified as White, 7751 (38.8%) identified as transgender women, 6489 (32.5%) identified as transgender men, and 5300 (26.6%) identified as nonbinary. After adjustment for sociodemographic factors and exposure to other types of gender-affirming care, undergoing 1 or more types of gender-affirming surgery was associated with lower past-month psychological distress (adjusted odds ratio [aOR], 0.58; 95% CI, 0.50-0.67; P < .001), past-year smoking (aOR, 0.65; 95% CI, 0.57-0.75; P < .001), and past-year suicidal ideation (aOR, 0.56; 95% CI, 0.50-0.64; P < .001). Conclusions and Relevance This study demonstrates an association between gender-affirming surgery and improved mental health outcomes. These results contribute new evidence to support the provision of gender-affirming surgical care for TGD people.
Network pharmacology-based screening of the active ingredients and mechanisms of Huangqi against aging

Abstract Studies have shown that Huangqi (HQ) has anti-aging efficacy. However, its active ingredients and mechanisms for anti-aging are still unclear. In this study, we will systematically screen the active ingredients of HQ and explore the possible mechanism of HQ in prevention from aging through network pharmacology technology. The main active ingredients of HQ were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The possible targets were predicted by TCMSP. The related targets for aging were obtained from GeneCards (The Human Gene Database) and Online Mendelian Inheritance in Man (OMIM) database. The common targets of HQ and aging were obtained using R 3.6. 3 software. The protein–protein interaction (PPI) network and the ingredient-target-disease network were constructed using Cytoscape 3.7. 2 software for visualization. In addition, the Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation of potential targets were performed using R 3.6. 3 software. Based on the screening conditions, 16 active ingredients and 28 drug targets were obtained. The PPI network contained 29 proteins, including PTGS2, AR, NOS2, and so on. GO functional enrichment analysis obtained 40 GO items (P < .05). KEGG pathway enrichment analysis obtained 110 aging related pathways (P < .05), including hypoxia inducible factor 1 signaling pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complication, among others. Sixteen effective ingredients of HQ and 28 targets against aging were identified through network pharmacology. Multiple pathways were involved in the effect of HQ on preventing aging.
A molecular toolkit for the green seaweed Ulva mutabilis

The green seaweed Ulva is an ecologically-important marine primary producer as well as a promising cash crop cultivated for multiple uses. Despite its importance, several molecular tools are still needed to better understand seaweed biology. Here, we report the development of a flexible and modular molecular cloning toolkit for the green seaweed Ulva mutabilis based on a Golden Gate cloning system. The toolkit presently contains 125 entry vectors, 26 destination vectors and 107 functionally validated expression vectors. We demonstrate the importance of endogenous regulatory sequences for transgene expression and characterize three endogenous promoters suitable to drive transgene expression. We describe two vector architectures to express transgenes via two expression cassettes or a bicistronic approach. The majority of selected transformants (50-80%) consistently give clear visual transgene expression. Furthermore, we made different marker lines for intracellular compartments after evaluating 13 transit peptides and 11 tagged endogenous Ulva genes. Our molecular toolkit enables the study of Ulva gain-of-function lines and paves the way for gene characterization and large-scale functional genomics studies in a green seaweed. One-sentence summary Molecular cloning tools allow to generate gain-of-function seaweed lines that will help to study seaweed biology.
Genetic reconstruction and phylogenetic analysis by 193 Y‐SNPs and 27 Y‐STRs in a Chinese Yi ethnic group

Yi is the seventh‐largest ethnic group in China and features mountainous regional characteristics. The Liangshan Yi Autonomous Prefecture is the largest Yi agglomeration with isolated geographical conditions, profoundly impeding genetic communication. Here, we investigated 427 unrelated males of Liangshan from 193 Y‐chromosome single nucleotide polymorphisms (Y‐SNPs) and 27 Y‐chromosome short tandem repeats (Y‐STRs) to reveal the genetic structure and paternal phylogeny of the group. The haplogroup diversity reached 0.9169 with 46 different subhaplogroups by 193 Y‐SNPs, and the haplotype diversity reached 0.9999 by 27 Y‐STR loci. Multidimensional scaling (MDS), N‐J tree, and Network were constructed to decipher and visualize the genetic relations between Yi and worldwide groups. Our results revealed: (1) the Network by Y‐STRs and Y‐SNPs showed the haplogroup D1a1a‐M15 in the Liangshan Yi population was a ramification of Tibetan groups’ expansion from west to east on the plateau; (2) the haplogroup distribution and the mismatch mutation analysis indicated the haplogroup O2a2b1a1a1a4a2‐Z25929 of Liangshan Yi derived from manifold Southeast Asian immigrants; (3) a high‐resolution Y‐SNPs panel is vital to depict accurate paternal derivations and build an integrated and refining genetic structure of ethnic groups.
Theoretical investigation of the impact of different timing schemes in hypofractionated radiotherapy.

PURPOSE This study compares the effectiveness of three fractionation schemes of equal fraction size, comprising five fractions of SBRT over five days, ten days, or fifteen days respectively. METHOD This comparative study is based on two tumour-control-probability (TCP) models that take into account tumour cell re-sensitization and repopulation during treatment; the Zaider-Minerbo-Stavreva (ZMS) and the Ruggieri-Nahum (RN) models. The ZMS model is further modified to include also re-sensitization according to the β mechanism of the linear-quadratic (LQ) model of cell killing. The modified version of the ZMS model is verified through fitting to the experimental data set of Fisher and Moulder. The study applies an idea used in a plan ranking methodology developed for the case when the specific values of the model parameters are not known. RESULTS The TCPs of the compared regimens are calculated for various values of the model parameters and for two different values of the dose per fraction. The TCPs are presented as 2-D functions of two of the model parameters for each model correspondingly. The differences between the TCPs of each of the prolonged regimens and the TCP of the every week day regimen are also calculated for each model. CONCLUSIONS Both models predict that the prolonged regimens are superior in terms of TCP to the every week-day ones for most of the studied cases; however this is shown to exist to a different degree by the two models. It is shown again to a different degree that reversed situations where the every week day schedule is better than the prolonged regimens are also possible. It is concluded that a 30% TCP difference observed in a clinical study in favour of the fifteen-days regimen is theoretically possible. However, the fifteen-days regimen is outperformed in terms of TCP by the every week day regimen in more cases than the regimen lasting ten days. Therefore the choice of a prolongation in time must be made with care.
Accuracy of 2D CT-Based Measurements of Rotational Alignment of the Femoral Component for Total Knee Arthroplasty

Purpose We aimed to investigate the accuracy of two-dimensional computed tomography (2D-CT)-based methods for measuring rotational alignment of the femoral component during total knee arthroplasty in comparison to reference values for three-dimensional (3D) reconstruction. Materials and Methods We selected the “most protruding transepicondylar axis section,” “most protruding posterior condylar line section,” and “distal femoral cut section” on 2D-CT images for 100 knees. We investigated posterior condylar angle (PCA) and condylar twist angle (CTA) values using three different methods on 2D-CT and compared to these values to those obtained using a 3D model. Results The mean PCA and CTA values were 2.8° and 7.0° on the 3D model and 2.0° to 2.1° and 5.9° to 6.0° on 2D-CT, respectively. Errors in PCA and CTA measurement included internal rotation of 0.8° and 1.1° with the 1-plane and 2-plane methods and 0.9° and 1.0° with the assumed resection method, respectively. Conclusion Mean errors in PCA and CTA values measured using three different methods on 2D-CT were not significantly different. However, PCA and CTA values measured on 2D-CT were approximately 1° smaller than their 3D values. Thus, we suggest that adding 1° to the mean PCA and CTA values obtained from a single plane of 2D-CT would provide values similar to those obtained from 3D reconstruction.
The structure of MgtE in the absence of magnesium provides new insights into channel gating

MgtE is a Mg2+ channel conserved in organisms ranging from prokaryotes to eukaryotes, including humans, and plays an important role in Mg2+ homeostasis. The previously determined MgtE structures in the Mg2+-bound, closed-state, and structure-based functional analyses of MgtE revealed that the binding of Mg2+ ions to the MgtE cytoplasmic domain induces channel inactivation to maintain Mg2+ homeostasis. There are no structures of the transmembrane (TM) domain for MgtE in Mg2+-free conditions, and the pore-opening mechanism has thus remained unclear. Here, we determined the cryo-electron microscopy (cryo-EM) structure of the MgtE-Fab complex in the absence of Mg2+ ions. The Mg2+-free MgtE TM domain structure and its comparison with the Mg2+-bound, closed-state structure, together with functional analyses, showed the Mg2+-dependent pore opening of MgtE on the cytoplasmic side and revealed the kink motions of the TM2 and TM5 helices at the glycine residues, which are important for channel activity. Overall, our work provides structure-based mechanistic insights into the channel gating of MgtE.
The Influence of Holder Pasteurization on the Diversity of the Human Milk Bacterial Microbiota Using High-Throughput DNA Sequencing

Background Human milk is the best food for infants; however, when breastfeeding is not possible, pasteurized milk from human milk banks is the best alternative. Little has been reported about variations in the bacterial microbiota composition of human milk after pasteurization. Research aim To characterize and compare the bacterial microbiota composition and diversity within human milk among Mexican mothers before and after the Holder pasteurization process. Methods A cross-sectional, observational, and comparative design was used. The effect of the pasteurization process on the bacterial composition and diversity of human milk samples of donors (N = 42) from a public milk bank was assessed before and after pasteurization by high throughput deoxyribonucleic acid sequencing of V3-16S rRNA gene libraries. Sequencing data were examined using the Quantitative Insights into Microbial Ecology software and Phyloseq in R environment. Results A varied community of bacteria was found in both raw and pasteurized human milk. The bacterial diversity of the milk samples was increased by the pasteurization, where some thermoduric bacteria of the phyla Proteobacteria, Firmicutes, and Actinobacteria were more abundant. The source tracker analysis indicated that at most 1.0% of bacteria may have come from another source, showing the safety of the process used to treat milk samples. Conclusion The pasteurization process increased the bacterial diversity. We selected taxa capable of surviving the process, which could proliferate after the treatment without being a risk for infants.
Key Characteristics of Residual Malaria Transmission in Two Districts in South-Eastern Tanzania—Implications for Improved Control

Abstract After 2 decades of using insecticide-treated nets (ITNs) and improved case management, malaria burden in the historically-holoendemic Kilombero valley in Tanzania has significantly declined. We review key characteristics of the residual transmission and recommend options for improvement. Transmission has declined by >10-fold since 2000 but remains heterogeneous over small distances. Following the crash of Anopheles gambiae, which coincided with ITN scale-up around 2005-2012, Anopheles funestus now dominates malaria transmission. While most infections still occur indoors, substantial biting happens outdoors and before bed-time. There is widespread resistance to pyrethroids and carbamates; An. funestus being particularly strongly-resistant. In short and medium-term, these challenges could be addressed using high-quality indoor residual spraying with nonpyrethroids, or ITNs incorporating synergists. Supplementary tools, eg, spatial-repellents may expand protection outdoors. However, sustainable control requires resilience-building approaches, particularly improved housing and larval-source management to suppress mosquitoes, stronger health systems guaranteeing case-detection and treatment, greater community-engagement and expanded health education.
Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways

Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro, inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived MNPs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal MNPs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.
Human-Centric Relation Segmentation: Dataset and Solution

Vision and language understanding techniques have achieved remarkable progress, but currently it is still difficult to well handle problems involving very fine-grained details. For example, when the robot is told to “bring me the book in the girl’s left hand”, most existing methods would fail if the girl holds one book respectively in her left and right hand. In this work, we introduce a new task named human-centric relation segmentation (HRS), as a fine-grained case of HOI-det. HRS aims to predict the relations between the human and surrounding entities and identify the relation-correlated human parts, which are represented as pixel-level masks. For the above exemplar case, our HRS task produces results in the form of relation triplets <inline-formula><tex-math notation="LaTeX">$\langle$</tex-math><alternatives><mml:math><mml:mo>〈</mml:mo></mml:math><inline-graphic xlink:href="liu-ieq1-3075846.gif"/></alternatives></inline-formula>girl [left hand], hold, book<inline-formula><tex-math notation="LaTeX">$\rangle$</tex-math><alternatives><mml:math><mml:mo>〉</mml:mo></mml:math><inline-graphic xlink:href="liu-ieq2-3075846.gif"/></alternatives></inline-formula> and exacts segmentation masks of the book, with which the robot can easily accomplish the grabbing task. Correspondingly, we collect a new Person In Context (PIC) dataset for this new task, which contains 17,122 high-resolution images and densely annotated entity segmentation and relations, including 141 object categories, 23 relation categories and 25 semantic human parts. We also propose a Simultaneous Matching and Segmentation (SMS) framework as a solution to the HRS task. It contains three parallel branches for entity segmentation, subject object matching and human parsing respectively. Specifically, the entity segmentation branch obtains entity masks by dynamically-generated conditional convolutions; the subject object matching branch detects the existence of any relations, links the corresponding subjects and objects by displacement estimation and classifies the interacted human parts; and the human parsing branch generates the pixelwise human part labels. Outputs of the three branches are fused to produce the final HRS results. Extensive experiments on PIC and V-COCO datasets show that the proposed SMS method outperforms baselines with the 36 FPS inference speed. Notably, SMS outperforms the best performing baseline <inline-formula><tex-math notation="LaTeX">$m$</tex-math><alternatives><mml:math><mml:mi>m</mml:mi></mml:math><inline-graphic xlink:href="liu-ieq3-3075846.gif"/></alternatives></inline-formula>-KERN with only 17.6 percent time cost. The dataset and code will be released at <uri>http://picdataset.com/challenge/index/</uri>.