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Herein the one‐pot thioesterification and hydrothiolation of α, β‐unsaturated esters with aliphatic thiols was reported at room temperature. The mechanism was indirectly revealed which α, β‐unsaturated thioester was the intermediate. The advantages of this method included transition‐metal‐free, mild conditions, broad substrate scope and good functional group tolerance. On the other hand, the hydrothiolation of α, β‐unsaturated aliphatic esters at room temperature was also developed. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Blood protein biomarkers demonstrate potential for Alzheimer's disease (AD) diagnosis. Limited studies examine the molecular changes in AD blood cells. METHODS: Bulk RNA‐sequencing of blood cells was performed on AD patients of Chinese descent (n = 214 and 26 in the discovery and validation cohorts, respectively) with normal controls (n = 208 and 38 in the discovery and validation cohorts, respectively). Weighted gene co‐expression network analysis (WGCNA) and deconvolution analysis identified AD‐associated gene modules and blood cell types. Regression and unsupervised clustering analysis identified AD‐associated genes, gene modules, cell types, and established AD classification models. RESULTS: WGCNA on differentially expressed genes revealed 15 gene modules, with 6 accurately classifying AD (areas under the receiver operating characteristics curve [auROCs] > 0.90). These modules stratified AD patients into subgroups with distinct disease states. Cell‐type deconvolution analysis identified specific blood cell types potentially associated with AD pathogenesis. DISCUSSION: This study highlights the potential of blood transcriptome for AD diagnosis, patient stratification, and mechanistic studies. Highlights: We comprehensively analyze the blood transcriptomes of a well‐characterized Alzheimer's disease cohort to identify genes, gene modules, pathways, and specific blood cells associated with the disease.Blood transcriptome analysis accurately classifies and stratifies patients with Alzheimer's disease, with some gene modules achieving classification accuracy comparable to that of the plasma ATN biomarkers.Immune‐associated pathways and immune cells, such as neutrophils, have potential roles in the pathogenesis and progression of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Key Clinical Message: There are no reports of application of inotuzumab ozogamicin (InO) for the treatment of MRD in r/r B‐ALL. We firstly report the efficacy of InO for a patient experienced morphological relapse after HSCT and molecular relapse after CART therapy. [ABSTRACT FROM AUTHOR]

Epigenetic alterations frequently participate in the onset of hematological malignancies. Histone deacetylases (HDACs) are essential for regulating gene transcription and various signaling pathways. Targeting HDACs has become a novel treatment option for hematological malignancies. Chidamide is the first oral selective HDAC inhibitor for HDAC1, HDAC2, HDAC3, and HDAC10 and was first approved for the treatment of R/R peripheral T‐cell lymphoma by the China Food and Drug Administration in 2014. Chidamide was also approved under the name Hiyasta (HBI‐8000) in Japan in 2021. In vitro studies revealed that chidamide could inhibit proliferation and induce apoptosis via cell cycle arrest and the regulation of apoptotic proteins. In clinical studies, chidamide was also efficacious in multiple myeloma, acute leukemia and myelodysplastic syndrome. This review includes reported experimental and clinical data on chidamide monotherapy or chidamide treatment in combination with chemotherapy for various hematological malignancies, offering a rationale for the renewed exploration of this drug. [ABSTRACT FROM AUTHOR]

Orbital angular momentum (OAM) has recently attracted increasing interest in optical communications for capacity scaling by OAM mode‐division multiplexing (MDM). OAM (de)multiplexer is crucial to the success of OAM‐MDM communications. Scalable and efficient dense OAM demultiplexing is highly desired, but full of challenges. Here, a quasi‐wavelet conformal mapping method is proposed and demonstrated to implement scalable and efficient dense OAM demultiplexing. The OAM mode is divided at the input plane into multiple concentric rings, which are mapped to multiple tilted plane waves and arranged side by side in a line. The engineered transformed light beams with periodic extension and increased length enable narrow focused spot width, reduced beam overlap, and suppressed demultiplexing crosstalk. The quasi‐wavelet conformal mapping method is compared with conventional log‐polar transformation scheme and hybrid log‐polar and fan‐out technique, and the crosstalk matrix for OAM demultiplexing is measured. Efficient OAM demultiplexing is demonstrated for 15 OAM modes (OAM−7 to OAM+7) with a maximum crosstalk of −12.1 dB in the experiment. Moreover, the method is also applied to system‐level data‐carrying OAM‐MDM communications with favorable performance. The demonstrated quasi‐wavelet conformal mapping method may pave the way for future ultrahigh capacity dense OAM‐MDM communications with a large number of OAM modes. [ABSTRACT FROM AUTHOR]

Yak has evolved specific adaptative mechanisms to high‐altitude environment. Up to date, only a few studies reported the DNA methylation in yak. In the present study, genome‐wide DNA methylome and transcriptome profiles in lung, mammary, and biceps brachii muscle tissues were compared between yak and three cattle breeds (Tibetan cattle, Sanjiang cattle, and Holstein cattle). The association between differentially expressed genes (DEGs) and differentially methylated regions (DMRs) was analyzed, and the biological functions of DEGs potentially driven by DMRs were explored by KEGG enrichment analysis. Finally, we found that yak‐specific DMRs‐driven DEGs were mainly involved in neuromodulation, respiration, lung development, blood pressure regulation, cardiovascular protection, energy metabolism, DNA repair, and immune functions. The higher levels of the key genes associated with these functions were observed in yak than in cattle, suggesting that DNA methylation might regulate these genes. Overall, the present study contributes basic data at the DNA methylation level to further understand the physiological metabolism in yak. Research Highlights: The difference in methylation level were observed in lung and mammary tissues.Yak‐specific DMRs‐driven DEGs were found.The higher levels of the key genes associated with these above functions were observed in yak than in cattle. [ABSTRACT FROM AUTHOR]

Hydraulic fracturing is the most widely used primary method for the stimulation of unconventional oil and gas resources. While knowledge of hydraulic fracture parameters is critical to reservoir productivity, predicting the fracture initiation is important for determining the complexity of the fracture network. Subcritical crack growth in reservoir rock plays an important role in forming fracture networks, but the understanding of the influence of fracturing conditions on subcritical crack growth is still lacking. In this paper, the subcritical crack growth behavior of sandstone and shale under ambient air, deionized (DI) water, and slick‐water conditions is studied. X‐ray diffraction analysis is done on the rock samples to determine their mineralogical composition, while tensile strength is measured by the Brazilian test. Then in Load Relaxation mode, a Double‐Torsion test (DT) is carried out under different conditions to study the subcritical crack growth of the samples. To further verify the influence of clay‐rich minerals, a similar analysis is performed on clay‐free granitic rock samples. The results of the tensile strength test and DT test demonstrate that the presence of clay minerals is the main reason for the difference in the subcritical crack growth behavior of shale and sandstone samples. DI water seems to better improve the subcritical crack growth compared with other test conditions. The value of the Subcritical Index (n) is smaller in a slick‐water environment than that in a DI water environment, revealing that slick water can better promote complex fracture propagation. [ABSTRACT FROM AUTHOR]

Philadelphia chromosome‐positive acute myeloid leukemia (Ph + AML) is a rare type of AML with a low survival rate and poor prognosis. We first report a Ph + AML patient who remained in long‐term remission after the combination of flumatinib and venetoclax, which could provide corresponding treatment ideas for clinical practice. The figure shows the treatment process of the patient and the dynamic changes in blood cell count during venetoclax and flumatinib. The BCR::ABL1 transcript was negative after two courses of the combination of venetoclax anf flumatinib. No serious adverse events occurred during the treatment, although hematological toxicity was observed. [ABSTRACT FROM AUTHOR]

Wavefront control lies at the heart of modern optics. Metasurfaces with specifically tailored resonators can encode different phases to two orthogonal polarization components, but suffer from wavelength‐dependent efficiency, sophisticated fabrication, and limited size. Liquid crystals, another excellent candidate for planar optics, are restricted to spin‐coupled conjugated phase modulations. Planar optics with spin‐decoupled functions is expected to release the multifunctionality of modern optics. Here, a spin‐decoupled transflective spatial light modulator is presented with a piecewise‐twisted anisotropic monolayer. The phases of reflected and transmitted light can be independently customized by preprogramming the initial orientations of the periodic helix and mirror‐symmetric dual‐twist configuration, respectively. A transflective orbital angular momentum encoder and decoder is demonstrated, which is simultaneously compatible with different multiplexing techniques. This work releases the multifunctionality of advanced planar optics and may upgrade existing devices in optical informatics. [ABSTRACT FROM AUTHOR]

We previously found that when tandemly expressed with SR69A‐VP8*, nonstructural protein 4 (NSP4) of the rotavirus Wa strain exerts a minor effect on elevating the antibody responses targeting the rotavirus antigen VP8* of the 60‐valent nanoparticle SR69A‐VP8* but could fully protect mice from diarrhea induced by the rotavirus strain Wa. In this study, we chose comparably less immunogenic norovirus 24‐valent P particles with homogenous (i.e., VP8* from rotavirus) and heterogeneous (i.e., protruding domain of norovirus) antigens and in more challenging rotavirus SA11 strain‐induced diarrhea mouse models to evaluate its main role in recombinant gastroenteritis virus‐specific vaccines. The results showed that although as an adjuvant NSP4 exerted limited effects on the elevation of norovirus‐specific or VP8*‐specific neutralizing antibody production, as an antigen it could confer potent protection, particularly when synergized with VP8*, in rotavirus SA11 strain‐induced diarrhea mouse models, possibly blocking the invasion of the intestinal wall by enterotoxin. NSP4 may be unnecessary for other recombinant vaccines as adjuvants, and its display mode should be evaluated specifically to avoid blocking coexpressed antigens in the norovirus P particles. [ABSTRACT FROM AUTHOR]

Incorporation of flexible monomer is regarded as a valid way to the chemical modification of the highly brittle poly(cyclohexene carbonate) (PCHC), which derived from the copolymerization of CO2 and cyclohexene oxide (CHO). However, toxic metal catalyst such as cobalt dominates these terpolymerizations which against the green development philosophy. Here, a series of environmentally benign aluminum porphyrin catalysts with different steric and electronic effects for the terpolymerization of CO2, CHO, and terminal epoxides with various flexible pendant alkyl groups to adjust the properties of PCHC is reported. The resulting terpolymers display a random distribution of cyclohexene carbonate along the backbone with a regulated terminal epoxide insertion from 30% to 70%. Moreover, the mechanical properties can be well regulated in a wide range indicating the feasibility of the present approach. The present study provides a green way to chemical modification of rigid PCHC. [ABSTRACT FROM AUTHOR]

Waning antibodies and rapidly emerging variants are challenges for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine development. Adjusting existing immunization schedules and further boosting strategies are under consideration. Here, the immune responses induced by an alum‐adjuvanted inactivated SARS‐CoV‐2 vaccine in mice were compared among immunization schedules with two or three doses. For the two‐dose schedule, a 0–28‐day schedule induced 5‐fold stronger spike‐specific IgG responses than a 0–14‐day schedule, with only a slight elevation of spike‐specific cellular immunity 14 days after the last immunization. A third homologous boost 2 or 5 months after the second dose for the 0–28‐day schedule slightly strengthened humoral responses (1.3‐fold for the 0–1–3‐month schedule, and 1.8‐fold for the 0–1–6‐month schedule) 14 days after the last immunization. Additionally, a third homologous boost (especially with the 0–1–3‐month schedule) induced significantly stronger cell‐mediated immunity than both two‐dose immunization schedules for all indexes tested, with a response similar to that induced by a one‐dose heterologous boost with BNT162b2 in clinical trials, according to cellular immunity analysis (1.5‐fold). These T cell responses were Th2 oriented, with good CD4+ and CD8+ memory. These results may offer clues for applying a homologous boosting strategy for alum‐adjuvanted inactivated SARS‐CoV‐2 vaccines. [ABSTRACT FROM AUTHOR]

Yaks display unique properties of the lung and heart, enabling their adaptation to high‐altitude environments, but the underlying molecular mechanisms are still largely unknown. In the present study, the proteome differences in lung and heart tissues were compared between yak (Bos grunniens) and three cattle strains (Bos taurus, Holstein, Sanjiang and Tibetan cattle) using the sequential window acquisition of all theoretical mass spectra/data‐independent acquisition (SWATH/DIA) proteomic method. In total, 51,755 peptides and 7215 proteins were identified. In the lung tissue, there were 162, 310 and 118 differential abundance proteins (DAPs) in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. In the heart tissue, there were 71, 57 and 78 DAPs in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DAPs were enriched for the retinol metabolism and toll‐like receptor categories in lung tissue. The changes in these two pathways may regulate hypoxia‐induced factor and immune function in yaks. Moreover, DAPs in heart tissues were enriched for cardiac muscle contraction, Huntington's disease, chemical carcinogenesis and drug metabolism‐cytochrome P450. Further exploration indicated that yaks may alter cardiac function through regulation of type 2 ryanodine receptor (RyR2) and Ca2+‐release channels. The present results are useful to further develop an understanding of the mechanisms underlying adaptation of animals to high‐altitude conditions. [ABSTRACT FROM AUTHOR]

There have been few reports on the treatment of central nervous system (CNS) acute myeloid leukemia (AML) relapse. This case study demonstrates that bevacizumab may be a viable treatment option when combined with IT chemotherapy as maintenance therapy for those with CNS leukemia. [ABSTRACT FROM AUTHOR]

Background: The emergence of promising compounds to lower lipoprotein(a) [Lp(a)] has increased the need for a precise characterisation and comparability assessment of Lp(a)‐associated cardiometabolic disease risk. This study aimed to evaluate the distribution of Lp(a) levels in a Chinese population and characterise the association with cardiometabolic diseases. Methods: We assessed data from individuals from the Cohort Study on Chronic Diseases of the General Community Population in the Beijing‐Tianjin‐Hebei Region project. All Lp(a) measurements were performed in the same hospital. The cardiometabolic diseases considered were coronary heart disease (CHD), stroke, hypertension and type 2 diabetes (T2DM). Results: A total of 25343 individuals were included in the study. The median level of Lp(a) was 11.9 mg/dl (IQR 5.9 to 23.7 mg/dl), and higher Lp(a) levels showed a significant concentration‐dependent association with CHD risk. Individuals with Lp(a) levels lower than the 25th percentile were at increased risk of hypertension (OR: 1.15, 95% CI: 1.06–1.25) and T2DM (OR: 1.15, 95% CI: 1.03–1.28); however, Lp(a) levels were not significantly associated with stroke. The addition of Lp(a) levels to the prognostic model led to a marginal but significant C‐index, integrated discrimination improvement and net reclassification improvement. Conclusions: In this large sample size study, we observed that elevated Lp(a) levels were significantly associated with CHD. Furthermore, we found that the lowest Lp(a) levels were also significantly associated with hypertension and T2DM. These results provide evidence for differential approaches to higher levels of Lp(a) in individuals with different cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

The direct ring‐opening polymerization (ROP) of propylene carbonate (PC) only affords oligomers with substantial unidentified by‐products, which hinders the efficient utilization of PC. Through detailed studies, for the first time, a careful mechanism involving the in situ release of propylene oxide (PO) from PC decarboxylation is proposed. Further, we report a novel strategy of copolymerization of PC/cyclic anhydrides via in situ capture of the formed intermediates. Results show that PC is successfully transformed into polyesters. Especially for the ring‐opening alternating copolymerization (ROAC) of PC/phthalic anhydride (PA), a variety of advantages are manifold: i) slow‐release of PO ensuring a perfectly alternating structure; ii) quantitative and fast transformation of PC; iii) visualization of polymerization process by a CO2 pressure gauge. Of importance, through tandem polymerizations, PC is fully transformed into polyesters and polycarbonates concurrently, thus achieving PC utilization with a high atom‐economy. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Thermoresponsive polymers with simultaneous biodegradability and signal "self‐reporting" outputs that meet for advanced applications are hard to obtain. To address this issue, we developed fluorescence signal "self‐reporting" biodegradable thermoresponsive polycarbonates through the immortal copolymerization of CO2 and oligoethylene glycol monomethyl ether‐functionalized epoxides in the presence of hydroxyl‐modified tetraphenylethylene (TPE‐OH). TPE‐OH was used as chain transfer agent to afford well‐defined polycarbonates with controlled molecular weight (6000—17000 g·mol–1) and aggregation‐induced emission characteristics. Through temperature‐dependent fluorescence intensity study, low critical solution transition of TPE‐labeled polycarbonates were determined and the fine details of thermal‐induced phase transition process were monitored. Further research indicated that temperature‐controlled aggregation and dissociation of TPE moieties are the main reason for fluorescence intensity variations. We anticipate that this work could offer a method to visualize the thermal transition process of thermoresponsive polycarbonates and broaden their application fields as smart materials. [ABSTRACT FROM AUTHOR]

The big data stored in massive open online course (MOOC) platforms have become a posed challenge in the Learning Analytics field to analyze the learning behavior of learners, and predict their respective performance, related especially to video lecture data, since most learners view the same online lecture videos. This helps to conduct a comprehensive analysis of such behaviors and explore various learning patterns in MOOC video interactions. This paper aims at presenting a visual analysis, which enables course instructors and education experts to analyze clickstream data that were generated by learner interaction with course videos. It also aims at predicting learner performance, which is a vital decision‐making problem, by addressing their issues and improving the educational process. This paper uses a long short‐term memory network (LSTM) on implicit features extracted from video‐clickstreams data to predict learners' performance and enable instructors to make measures for timely intervention. Results show that the accuracy rate of the proposed model is 89%–95% throughout course weeks. The proposed LSTM model outperforms baseline Deep learning (GRU) and simple recurrent neural network by accuracy of 90.30% in the "Mining of Massive Datasets" course, and the "Automata Theory" accuracy is 89%. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) had led to a serious public health crisis, and no specific treatments or vaccines are available yet. A nucleocapsid protein (NP)‐based enzyme‐linked immunosorbent assay (ELISA) detection method is not only important in disease diagnosis, but is required for the evaluation of vaccine efficacy during the development of an inactivated SARS‐CoV‐2 vaccine. In this study, we expressed both the NP and N‐terminally truncated NP (ΔN‐NP) of SARS‐CoV‐2 in an Escherichia coli expression system and described the purification of the soluble recombinant NP and ΔN‐NP in details. The identities of the NP and ΔN‐NP were confirmed with mass spectrometry. We then used immunoglobulin G detection ELISAs to compare the sensitivity of NP and ΔN‐NP in detecting anti‐SARS‐CoV‐2 antibodies. ΔN‐NP showed greater sensitivity than NP in the analysis of serially diluted sera from mice and rabbits vaccinated with inactive SARS‐CoV‐2 and in human sera diluted 1:400. ΔN‐NP showed a positive detection rate similar to that of the SARS‐CoV‐2 S protein in human sera. We conclude that ΔN‐NP is a better serological marker than NP for evaluating the immunogenicity of inactivated SARS‐CoV‐2. Highlights: ΔN‐NP showed greater sensitivity than NP for evaluating the immunogenicity of inactivated SARS‐CoV‐2.We described in detail the expression and purification of both recombinant soluble NP and ΔN‐NP of SARS‐CoV‐2 in an E. coli expression system. [ABSTRACT FROM AUTHOR]

Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has developed into a global pandemic within a matter of months. While subunit vaccines are one of the prominent options for combating coronavirus disease 2019 (COVID‐19), the immunogenicity of spike protein‐based antigens remains unknown. When immunized in mice, the S1 domain induced much higher IgG and IgA antibody levels than the receptor‐binding domain (RBD) and more efficiently neutralized SARS‐CoV‐2 when adjuvanted with alum. It is inferred that a large proportion of these neutralization epitopes are located in the S1 domain but outside the RBD and that some of these are spatial epitopes. This finding indicates that expression systems with posttranslational modification abilities are important to maintain the natural configurations of recombinant spike protein antigens and are critical for effective COVID‐19 vaccines. Further, adjuvants prone to a Th1 response should be considered for S1‐based subunit COVID‐19 vaccines to reduce the potential risk of antibody‐dependent enhancement of infection. Highlights: Antibodies induced by the S1 domain neutralized SARS‐Cov‐2 more efficiently than those induced by the receptor‐binding domain (RBD). Antibodies induced by the S1 domain produced from HEK293K cells neutralized SARS‐Cov‐2 more efficiently than those induced by the S1 domain produced from E. coli. Both the S1 domain and the RBD induced a highly Th2 response when adjuvanted with alum. [ABSTRACT FROM AUTHOR]

Acute dietary salt intake may cause an elevation in blood pressure (BP). The study aimed to assess the acute effect of saline loading on BP in subjects with different levels of salt intake. This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. The sodium excretion in the 24‐hour urine was calculated for estimating the level of salt intake. Subjects were performed an acute oral saline loading test (1 L), and data of 2019 participants were included for analyses. Multivariate linear regression and stratified analyses were performed to identify associations between 24‐hour urinary sodium (24hUNa) with BP changes. Due to saline loading, systolic BP (SBP), pulse pressure, and urinary sodium concentration were significantly increased, while diastolic BP, heart rate, and urinary potassium concentration were significantly decreased. The SBP increments were more significant in subjects with lower salt intake, normotensives, elders, males, smokers, and drinkers. There was a significant linear negative dose‐response association between SBP increment with 24hUNa (β = −0.901, 95% CI: −1.253, −0.548), especially in lower salt intake individuals (β = −1.297, 95% CI: −2.338, −0.205) and hypertensive patients (β = −1.502, 95% CI: −2.037, −0.967). After excluding patients who received antidiabetic or antihypertensive medicines, the effects of negative associations weakened but remained significantly. In conclusion, acute salt loading leads to an increment in SBP, and the increased SBP was negatively related with 24hUNa. This study indicated avoiding acute salt loading was important for escaping acute BP changes, especially in lower salt intake populations. [ABSTRACT FROM AUTHOR]

Yak is an important livestock animal for the people indigenous to the harsh, oxygen‐limited Qinghai‐Tibetan Plateau and Hindu Kush ranges of the Himalayas. The yak genome was sequenced in 2012, but its assembly was fragmented because of the inherent limitations of the Illumina sequencing technology used to analyse it. An accurate and complete reference genome is essential for the study of genetic variations in this species. Long‐read sequences are more complete than their short‐read counterparts and have been successfully applied towards high‐quality genome assembly for various species. In this study, we present a high‐quality chromosome‐scale yak genome assembly (BosGru_PB_v1.0) constructed with long‐read sequencing and chromatin interaction technologies. Compared to an existing yak genome assembly (BosGru_v2.0), BosGru_PB_v1.0 shows substantially improved chromosome sequence continuity, reduced repetitive structure ambiguity, and gene model completeness. To characterize genetic variation in yak, we generated de novo genome assemblies based on Illumina short reads for seven recognized domestic yak breeds in Tibet and Sichuan and one wild yak from Hoh Xil. We compared these eight assemblies to the BosGru_PB_v1.0 genome, obtained a comprehensive map of yak genetic diversity at the whole‐genome level, and identified several protein‐coding genes absent from the BosGru_PB_v1.0 assembly. Despite the genetic bottleneck experienced by wild yak, their diversity was nonetheless higher than that of domestic yak. Here, we identified breed‐specific sequences and genes by whole‐genome alignment, which may facilitate yak breed identification. [ABSTRACT FROM AUTHOR]

Yak is the unique Bovidae species in the Qinghai‐Tibetan Plateau. A previous proteomic study has compared the yak muscle tissue to one cattle strain using the isobaric tags for relative and absolute quantification approach. In this study, to further investigate the molecular mechanisms underlying yak adaptation, the proteomic profiles of gluteus were compared between yak and one moderate‐altitude cattle strain (Tibetan cattle) and two low‐altitude cattle strains (Holstein and Sanjiang cattle) using a label‐free quantitative method. The comparisons identified 20, 364, 143 upregulated proteins and 4, 6, 37 downregulated proteins in yak, compared with Tibetan, Holstein, and Sanjiang cattle, respectively. Protein–protein interaction analysis indicated that these differentially expressed proteins were mainly related to "oxidative phosphorylation" and "electron transport chain." Further analysis revealed that NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11, NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4, cytochrome C oxidase subunit 6A2, mitochondrial and cytochrome c oxidase subunit NDUFA4 were all increased in the yak, suggesting that yak might increase mitochondrial capacity to sustain metabolic rates under high altitude conditions, which might be a long‐term adaptive mechanism underlying adaptation to high altitude environments. Yak increased the level of thioredoxin reductase 2 to protect themselves from oxidative damages. Moreover, the increased expression levels of phosphatidylinositol 4,5‐bisphosphate 3‐kinase catalytic subunit alpha isoform and caveolin‐1 in yak suggested that yaks promoted glucose uptake for adaptation to high altitude. These results provided more information to better understand the molecular mechanisms underlying yak adaption. Highlights: Yak displays unique lung and heart properties to adapt high‐altitude environments.Yak minimized the requirement of oxygen and avoid the accumulation of reactive oxygen species.Yak increased the level of glutathione S‐transferase class‐mu 1 to protect themselves from oxidative damages. [ABSTRACT FROM AUTHOR]

Salt‐sensitive hypertension (SSH) is an independent risk factor for cardiovascular disease. The regulation of long non‐coding RNAs, mRNAs and competing endogenous RNAs (ceRNAs) in the pathogenesis of SSH is uncertain. An RNA microarray was performed to discover SSH‐associated differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs), and 296 DElncRNAs and 44 DEmRNAs were identified, and 247 DElncRNAs and 44 DEmRNAs among these RNAs were included in the coexpression network. The coregulatory network included 23 ceRNA loops, and six hub RNAs (lnc‐ILK‐8:1, lnc‐OTX1‐7:1, lnc‐RCAN1‐6:1, GIMAP8, SUV420H1 and PIGV) were identified for further population validation. The ceRNA correlations among lnc‐OTX1‐7:1, hsa‐miR‐361‐5p and GIMAP8 were confirmed in SSH and SRH patients. A larger‐sample validation confirmed that GIMAP8, SUV420H1 and PIGV were differentially expressed between the SSH and SRH groups. In addition, SUV420H1 was included in the SSH screening model, and the area under the curve of the model was 0.720 (95% CI: 0.624‐0.816). Our study explored the transcriptome profiles of SSH and constructed a ceRNA network to help elucidate the mechanism of SSH. In addition, SUV420H1 was identified as a hub element that participates in SSH transcriptional regulation and as a potential biomarker for the early diagnosis of SSH. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a leading cause of mortality in the elderly. Genetics studies suggest that AD is polygenic in nature; thus, an individual's risk of AD can be predicted by polygenic risk score (PRS) models. Of these models, the deep learning models more accurately capture nonlinear interactions among different genetic risks and are more suitable for modeling disease polygenic risk. Method: We used the neural network‐based deep learning models to evaluate the polygenic risk of AD. Meanwhile, we examined the associations of resultant PRSs and plasma protein biomarkers for AD by regression analysis. We also identified the biological pathways that contribute to the polygenic risk using Gene Set Enrichment Analysis. Result: We found that the resultant PRSs of AD are associated with the levels of specific AD plasma protein biomarkers, including amyloid beta and p‐tau181, as well as changes in the activity of specific biological events, such as TNF‐α and cytokine‐related pathways. Conclusion: Our findings suggest that AD polygenic risk is associated with AD progression and modulates immune‐associated pathways. They also highlight the potential use of deep learning methods in investigating the underlying genetic mechanisms of AD. [ABSTRACT FROM AUTHOR]

An effective and inexpensive organocatalyst tetrabutylammonium fluoride (TBAF) was developed for the reductive functionalization of CO2 with amines to selectively afford formamides or methylamines by employing hydrosilanes. Hydrosilanes with different substituents show discriminatory reducing activity. Thus, the formation of formamides and further reduction products, that is, methylamines could be controlled by elegantly tuning hydrosilane types. Formamides were obtained exclusively under an atmospheric pressure of CO2 with triethoxysilane. Using phenylsilane as a reductant, methylamines were attained with up to 99 % yield at 50 °C coupled to a complete deoxygenation of CO2. The crucial intermediate silyl formate in the formylation step was identified and thereby a tentative mechanism involving the fluoride-promoted hydride transfer from the hydrosilane to CO2/formamide was proposed. Striking features of this metal-free protocol are formylation and methylation of amines by reductive functionalization of CO2 with hydrosilanes and mild reaction conditions. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a leading cause of mortality in the elderly. Genetics studies have identified variants associated with AD. Moreover, Polygenic score analysis can infer the risk of developing AD solely on the basis of genotype information. Method: Whole‐genome sequencing was performed in 2 AD cohorts recruited from mainland China (n = 2,340) and Hong Kong (n = 1,009). Genotype and phenotype data were input into a neural network model that output a polygenic score. Regression analysis was subsequently conducted to examine the associations between the resultant polygenic scores and AD plasma biomarkers. Result: The resultant polygenic scores were associated with AD pathogenesis and the levels of specific AD plasma biomarkers in the Chinese population. Conclusion: The results suggest that deep‐learning methods have utility for investigating the underlying mechanisms of AD and promote the possibility of developing a genotype‐based strategy for AD risk prediction. [ABSTRACT FROM AUTHOR]

Background: Differences between men and women are common in Alzheimer's disease and related dementias (ADRD) research. What do they mean? To answer this, rigorous measurement is needed. We investigated current methods being used in ADRD research to measure sex/gender. Method: An online survey was sent to 38 federally‐funded Alzheimer's Disease Research Centers (ADRCs), which are required to maintain research cohorts, and 38 federally‐funded cohort studies on aging and cognition in the U.S. The response rate was 65.8% (n=50). The survey assessed whether studies enrolled men and women and study protocols for all measures of sex and gender. Results: One or more personnel from 25 ADRCs/ADCs and 25 cohort studies completed the survey from October to December 2020. Of the 50 ADRCs/ADCs and cohort studies, all enrolled men and all but two cohort studies enrolled women. The majority indicated no documented definitions of "man" or "woman": 23/25 (92%) ADRCs/ADCs and 20/25 (80%) cohort studies. Of the seven reporting study definitions, sex/gender definitions included the following: male vs. female (n=2), biologic sex (n=1), defined by another data source ("NACC form" n=1), or only noted that sex/gender was self‐reported (n=3). sIn 4/5 instances where multiple personnel reported on a ADRC/ADC or cohort study, reports were inconsistent [e.g., "sex" vs "gender" (n=1) or named "sex" vs unlisted (n=3)]. Most studies (20/25 ADRCs/ADCs, 17/25 cohort studies) had only one measure of sex/gender. In total, 52 measures of sex/gender were described: self‐report (n=43), direct observation (n=5), obtained from secondary source (n=3), and biologic specimen (n=1). Self‐report measures asked participants to report whether they identified as "male or female" or "man or woman." Conclusion: ADRD research efforts in the U.S. appear to consistently enroll men and women. However, there is a need to define these terms in ways that ensure inclusivity, representation, and consistency in data collection. It is essential to expand measures of sex/gender in ADRD research beyond self‐report data to social, behavioral, and biologic markers in order to aid discovery of specific pathways that affect ADRD outcomes. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Thermoresponsive polymers with simultaneous biodegradability and signal "self‐reporting" outputs that meet for advanced applications are hard to obtain. To address this issue, we developed fluorescence signal "self‐reporting" biodegradable thermoresponsive polycarbonates through the immortal copolymerization of CO2 and oligoethylene glycol monomethyl ether‐functionalized epoxides in the presence of hydroxyl‐modified tetraphenylethylene (TPE‐OH). TPE‐OH was used as chain transfer agent to afford well‐defined polycarbonates with controlled molecular weight (6000—17000 g·mol–1) and aggregation‐induced emission characteristics. Through temperature‐dependent fluorescence intensity study, low critical solution transition of TPE‐labeled polycarbonates were determined and the fine details of thermal‐induced phase transition process were monitored. Further research indicated that temperature‐controlled aggregation and dissociation of TPE moieties are the main reason for fluorescence intensity variations. We anticipate that this work could offer a method to visualize the thermal transition process of thermoresponsive polycarbonates and broaden their application fields as smart materials. [ABSTRACT FROM AUTHOR]

Catalytic conversion of CO2 to give value ‐ added chemicals at atmospheric pressure still remains challenging. In this study, a fluoride ‐ promoted metal ‐ free protocol has been developed for the highly efficient and selective reductive functionalization of CO2 with amines and hydrosilanes under mild conditions. Formamide and methylamines could be accessed by tuning the hydrosilane type. This protocol offers chemoselective two ‐ or six ‐ electron reduction of CO2 in combination with C−N bond construction. More information can be found in the Full Paper by L. ‐ N. He et al. on page 16489 ff. [ABSTRACT FROM AUTHOR]