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The evolutionary direction of gonochorism and hermaphroditism is an intriguing mystery to be solved. The special transient hermaphroditic stage makes the little yellow croaker (Larimichthys polyactis) an appealing model for studying hermaphrodite formation. However, the origin and evolutionary relationship between of L. polyactis and Larimichthys crocea, the most famous commercial fish species in East Asia, remain unclear. Here, we report the sequence of the L. polyactis genome, which we found is ~706 Mb long (contig N50 = 1.21 Mb and scaffold N50 = 4.52 Mb) and contains 25,233 protein-coding genes. Phylogenomic analysis suggested that L. polyactis diverged from the common ancestor, L. crocea, approximately 25.4 million years ago. Our high-quality genome assembly enabled comparative genomic analysis, which revealed several within-chromosome rearrangements and translocations, without major chromosome fission or fusion events between the two species. The dmrt1 gene was identified as the male-specific gene in L. polyactis. Transcriptome analysis showed that the expression of dmrt1 and its upstream regulatory gene (rnf183) were both sexually dimorphic. Rnf183, unlike its two paralogues rnf223 and rnf225, is only present in Larimichthys and Lates but not in other teleost species, suggesting that it originated from lineage-specific duplication or was lost in other teleosts. Phylogenetic analysis shows that the hermaphrodite stage in male L. polyactis may be explained by the sequence evolution of dmrt1. Decoding the L. polyactis genome not only provides insight into the genetic underpinnings of hermaphrodite evolution, but also provides valuable information for enhancing fish aquaculture.

To evaluate the effectiveness of an online program on nurse preceptors' knowledge and self-efficacy in their roles to support students' clinical education, and to examine their online experience.Professional development of nurse preceptors is paramount to fostering work readiness of future graduate nurses on entering the workforce. The support from academic institutions in developing preceptors' roles in clinical teaching and assessment is pivotal.This study employed a mixed-methods design.A total of 59 nurse preceptors from six healthcare institutions participated in an online preceptor program by collaborating with academic educators in facilitating student clinical learning and assessment through telesimulation following web-based instruction. Pre-test and post-tests were administered to evaluate the preceptors' knowledge and self-efficacy in their roles. Survey questionnaires and focus group discussions were conducted to evaluate their online experience. SQUIRE 2.0 guidelines were applied.The preceptors demonstrated significant improvements (p .001) in knowledge and levels of self-efficacy in their preceptor roles immediately and 1 month after the program. The following four themes emerged from their learning experiences: 'interactive learning approach', 'academic-practice collaboration', 'better understanding of clinical assessment tool' and 'application of teaching strategies'. The preceptors reported positively on their motivation to learn using the web-based instruction and on their telesimulation experience.The study findings demonstrated effectiveness and feasibility of an online preceptor program to enhance preceptors' roles in supporting nursing students' transition to clinical practice, using a mix of web-based technologies to provide preceptors with self-directed and experiential learning approaches.This study contributed to the development of an innovative online preceptor program that provided opportunity for academic-clinical collaboration and has broad applicability. The telesimulation created robust remote simulation experiences for preceptors, allowing them to collaborate with academic educators in facilitating students' clinical practice amid the COVID-19 pandemic.

Platelets may serve as a perfect peripheral source for exploring diagnostic biomarkers for Alzheimer's disease (AD); however, the molecular linkage between platelet and the brain is missing. To find the common altered and driving molecules in both brain and the platelet, we performed an integrated analysis of our platelet omics and brain omics reported in the literature, and analyzed their correlations with AD-specific pathology and cognitive impairment. By integrating the gene and protein expression profiles from 269 AD patients, we deduced 239 differentially expressed proteins (DEPs) appeared in both brain and the platelet, and 70.3% of them had consistent changes. Further analysis demonstrated that the altered brain and peripheral regulations were pinpointed into 10 imbalanced pathways. We also found that 117 DEPs, including ADAM10, were closely associated to the AD-specific β-amyloid and tau pathologies; and the changes of IDH3B and RTN1 had a potential diagnostic value for cognitive impairment analyzed by machine learning. Finally, we identified that HMOX2 and SERPINA3 could serve as driving molecules in neurodegeneration, and they were increased and decreased in AD patients, respectively. Together, this integrated brain and platelet omics provides a valuable resource for establishing efficient peripheral diagnostic biomarkers and potential therapeutic targets for AD.

The influence of maximum principal stress level on true-triaxial unloading behaviors and the failure mechanism of sandstone samples were comprehensively investigated by laboratory tests and discrete element simulations. The results show that the level of σ1 at unloading point significantly affects the deformation and failure characteristics of sandstone samples under true-triaxial unloading conditions. As the level of σ1 at unloading point increases, the ultimate bearing capacity of sandstone sample is increasingly strengthened, while the sample collapses more easily during the unloading process, and the failure mode of sandstone sample changes from mixed tensile-shear failure to shear failure. With the increase in the level of σ1 at unloading point, the accumulative micro-cracks at the unloading point and micro-crack generation rate during the unloading phase exhibit an increasing trend, while the sum of micro-cracks at the unloading phase and the ratio between the amount of tensile micro-cracks and shear micro-cracks roughly show a downward trend. The formation of macro fracture in sandstone sample is closely related to the stress conditions and material inhomogeneity. The tensile fracture in the upper right part of sample when the level of σ1 is relatively low should be attributed to the superiority in tensile contacts between particles in terms of contact number and corresponding tensile force.

Adult patients with relapsed or refractory T‐cell acute lymphoblastic leukemia (R/R‐T‐ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G‐CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R‐T‐ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T‐cell precursor (ETP) (n = 26) and non‐ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo‐HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non‐CR). With a median follow‐up time of 12 months, the estimated 2‐year overall survival and event‐free survival were 68.8% (95% CI, 47.3%‐83.0%) and 56.5% (95% CI, 37.1%‐71.9%), respectively. The CAG regimen was well‐tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R‐T‐ALL and providing a better bridge to transplantation., Adult patients with relapsed or refractory T‐cell acute lymphoblastic leukemia (R/R‐T‐ALL) have limited therapeutic options and extremely poor prognosis (CR rate

The selective catalytic reduction (SCR) of NOx with NH3 to N2 with supported V2 O5 (-WO3 )/TiO2 catalysts is an industrial technology used to mitigate toxic emissions. Long-standing uncertainties in the molecular structures of surface vanadia are clarified, whereby progressive addition of vanadia to TiO2 forms oligomeric vanadia structures and reveals a proportional relationship of SCR reaction rate to [surface VOx concentration]2 , implying a 2-site mechanism. Unreactive surface tungsta (WO3 ) also promote the formation of oligomeric vanadia (V2 O5 ) sites, showing that promoter incorporation enhances the SCR reaction by a structural effect generating adjacent surface sites and not from electronic effects as previously proposed. The findings outline a method to assess structural effects of promoter incorporation on catalysts and reveal both the dual-site requirement for the SCR reaction and the important structural promotional effect that tungsten oxide offers for the SCR reaction by V2 O5 /TiO2 catalysts.

Tau accumulation and cholinergic impairment are characteristic pathologies in Alzheimer's disease (AD). However, the causal role of tau accumulation in cholinergic lesion is elusive. Here, we observed an aberrant tau accumulation in the medial septum (MS) of 3xTg and 5xFAD mice, especially in their cholinergic neurons. Overexpressing hTau in mouse MS (MShTau) for 6 months but not 3 months induced spatial memory impairment without changing object recognition and anxiety‐like behavior, indicating a specific and time‐dependent effect of MS‐hTau accumulation on spatial cognitive functions. With increasing hTau accumulation, the MShTau mice showed a time‐dependent cholinergic neuron loss with reduced cholinergic projections to the hippocampus. Intraperitoneal administration of donepezil, a cholinesterase inhibitor, for 1 month ameliorated the MS‐hTau‐induced spatial memory deficits with preservation of MS–hippocampal cholinergic pathway and removal of tau load; and the beneficial effects of donepezil was more prominent at low dose. Proteomics revealed that MS‐hTau accumulation deregulated multiple signaling pathways with numerous differentially expressed proteins (DEPs). Among them, the vacuolar protein sorting‐associated protein 37D (VP37D), an autophagy‐related protein, was significantly reduced in MShTau mice; the reduction of VP37D was restored by donepezil, and the effect was more significant at low dose than high dose. These novel evidences reveal a causal role of tau accumulation in linking MS cholinergic lesion to hippocampus‐dependent spatial cognitive damages as seen in the AD patients, and the new tau‐removal and autophagy‐promoting effects of donepezil may extend its application beyond simple symptom amelioration to potential disease modification., Proposed working model: Medial septum (MS) tau accumulation disrupts MS–hippocampus cholinergic pathway and impairs hippocampus‐associated spatial memory as seen on patients with Alzheimer's disease (AD). In addition to traditional cholinesterase inhibition, low‐dose donepezil exerts novel tau‐removal and autophagy‐promoting effects, efficiently rescuing MS‐htau‐induced memory loss. Our results supplement tau toxicity and the new findings on donepezil may extend its application beyond simple symptom amelioration to potential disease modification; the latter may help physicians to optimize dosing in donepezil treatment on AD.

Memory loss is the most common clinical sign in Alzheimer's disease (AD); thus, searching for peripheral biomarkers to predict cognitive decline is promising for early diagnosis of AD. As platelets share similarities to neuron biology, it may serve as a peripheral matrix for biomarkers of neurological disorders. Here, we conducted a comprehensive and in‐depth platelet proteomic analysis using TMT‐LC‐MS/MS in the populations with mild cognitive impairment (MCI, MMSE = 18–23), severe cognitive impairments (AD, MMSE = 2–17), and the age‐/sex‐matched normal cognition controls (MMSE = 29–30). A total of 360 differential proteins were detected in MCI and AD patients compared with the controls. These differential proteins were involved in multiple KEGG pathways, including AD, AMP‐activated protein kinase (AMPK) pathway, telomerase RNA localization, platelet activation, and complement activation. By correlation analysis with MMSE score, three positively correlated pathways and two negatively correlated pathways were identified to be closely related to cognitive decline in MCI and AD patients. Partial least squares discriminant analysis (PLS‐DA) showed that changes of nine proteins, including PHB, UQCRH, CD63, GP1BA, FINC, RAP1A, ITPR1/2, and ADAM10 could effectively distinguish the cognitively impaired patients from the controls. Further machine learning analysis revealed that a combination of four decreased platelet proteins, that is, PHB, UQCRH, GP1BA, and FINC, was most promising for predicting cognitive decline in MCI and AD patients. Taken together, our data provide a set of platelet biomarkers for predicting cognitive decline which may be applied for the early screening of AD., Deep profiling of platelet proteome in healthy aging subjects and MCI/AD cases. Some individual candidate biomarkers in platelets closely reflect the pathophysiological process of AD. The identified novel platelet combination biomarkers can distinguish healthy aging subjects and cognitively impaired subjects.

Intracellular accumulating of the hyperphosphorylated tau plays a pivotal role in neurodegeneration of Alzheimer disease (AD), but the mechanisms underlying the gradually aggravated tau hyperphosphorylation remain elusive. Here, we show that increasing intracellular tau could upregulate mRNA and protein levels of TRPC1 (transient receptor potential channel 1) with an activated store‐operated calcium entry (SOCE), an increased intraneuronal steady‐state [Ca2+]i, an enhanced endoplasmic reticulum (ER) stress, an imbalanced protein kinases and phosphatase, and an aggravated tauopathy. Furthermore, overexpressing TRPC1 induced ER stress, kinases‐phosphatase imbalance, tau hyperphosphorylation and cognitive deficits in cultured neurons and mice, while pharmacological inhibiting or knockout TRPC1 attenuated the hTau‐induced deregulations in SOCE, ER homeostasis, kinases‐phosphatase balance, and tau phosphorylation level with improved synaptic and cognitive functions. Finally, an increased CCAAT‐enhancer‐binding protein (C/EBPβ) activity was observed in hTau‐overexpressing cells and the hippocampus of the AD patients, while downregulating C/EBPβ by siRNA abolished the hTau‐induced TRPC1 upregulation. These data reveal that increasing intracellular tau can upregulate C/EBPβ‐TRPC1‐SOCE signaling and thus disrupt phosphorylating system, which together aggravates tau pathologies leading to a chronic neurodegeneration., Increasing tau accumulation leads to hyperactivated SOCE, ER stress, and kinases‐phosphatase imbalance through C/EBPβ‐mediated upregulation of TRPC1, which thereby induces persistent and aggravated tau hyperphosphorylation and cognitive deficits in cultured neurons or mice, while pharmacological inhibiting or knockout TRPC1 attenuated the hTau‐induced dysregulations in SOCE, ER homeostasis, kinases‐phosphatase balance, and tau phosphorylation level with improved synaptic and cognitive functions.

Endoplasmic reticulum (ER) stress is involved in Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we injected tunicamycin (TM), a recognized ER stress inducer, into the brain ventricle of Sprague‐Dawley (SD) rats to induce the unfolded protein response (UPR), demonstrated by the enhanced phosphorylation of pancreatic ER kinase (PERK), inositol‐requiring enzyme‐1 (IRE‐1) and activating transcription factor‐6 (ATF‐6). We observed that UPR induced spatial memory deficits and impairments of synaptic plasticity in the rats. After TM treatment, GSK‐3β was activated and phosphorylation of cAMP response element binding protein at Ser129 (pS129‐CREB) was increased with an increased nuclear co‐localization of pY126‐GSK‐3β and pS129‐CREB. Simultaneous inhibition of GSK‐3β by hippocampal infusion of SB216763 (SB) attenuated TM‐induced UPR and spatial memory impairment with restoration of pS129‐CREB and synaptic plasticity. We concluded that UPR induces AD‐like spatial memory deficits with mechanisms involving GSK‐3β/pS129‐CREB pathway.

TiO2 has great potential in the application of biocompatible supercapacitors. Unfortunately, because of semiconducting nature, TiO2 exhibit poor electrical conductivity and extremely low specific capacitance. Doping with other atoms is a facile way to enhance electrochemical activity of TiO2. However, the restricted solubility of substitutional dopants in bulk largely impaired the effectiveness of doping, resulting in quite limited capacitance improvement. To overcome this issue, we propose a two-step approach to efficiently dope TiO2 nanobelts with nitrogen. High level nitrogen doping (7.2 at.%) was achieved in the distinct crystalline core/disordered shell structured TiO2, boosting the specific capacitance of TiO2 from 4 F g-1 to 216 F g-1. Employing compressible, light weight three-dimensional graphene as current collector, the symmetrical cell exhibits a volumetric energy density of 9.6 mWh cm-3, highly comparable with the supercapacitors based on conventional pseudocapacitive materials. These encouraging findings unambiguously smash the capacitance bottleneck of TiO2 and shed a light of TiO2 in energy storage systems.

Objectives To evaluate the effects of listening to brainwave music (BWM), which is composed by individual electroencephalogram (EEG) signals, in relieving orthodontic pain, compared to cognitive behavioural therapy (CBT), an established psychotherapy in pain management. Methods Thirty-six participants matched for age, gender and anxiety/pain levels were randomly assigned to the BWM group (n = 12), the CBT group (n = 12) or the control group (n = 12). Baseline resting EEG data were fabricated into BWM for the BWM group. EEG signals and pain perception [assessed by visual analogue scale (VAS)] of participants were recorded for the first week after orthodontic appliances placement. EEG data were analysed by multiple approaches. Results Brainwave music and CBT groups presented significantly lower pain perception than the control group on days 1–4. According to EEG analysis outcomes, the BWM group showed improved functional connectivity among different brain regions, lower EEG complexity and enhanced power in theta and alpha bands, compared to CBT and control groups, especially on day 2. Differences were clustered in the prefrontal, frontal, parietal and occipital regions, whilst the EEG parameters had negligible linear association with VAS scores. Conclusions Brainwave music is effective in controlling orthodontic pain, possibly via restoring functional connectivity and brain regularity influenced by pain.