Terahertz fiber link using dielectric silicon waveguide interface.

Nascent data-intensive emerging technologies are mandating low-loss, short-range interconnects, whereas existing interconnects suffer from high losses and low aggregate data throughput owing to a lack of efficient interfaces. Here, we report an efficient 22-Gbit/s terahertz fiber link using a tapered silicon interface that serves as a coupler between the dielectric waveguide and hollow core fiber. We investigated the fundamental optical properties of hollow-core fibers by considering fibers with 0.7-mm and 1-mm core diameters. We achieved a coupling efficiency of ∼ 60% with a 3-dB bandwidth of 150 GHz in the 0.3-THz band over a 10 cm fiber.

A "Double-Locked" and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy.

Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the "double-locked" strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-ß-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of ß-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first "key") and pH (second "key"), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy.

All-silicon, low-cross-talk terahertz waveguide crossing based on effective medium.

All-silicon effective-medium-clad waveguides are a promising candidate for an integrated terahertz platform with high efficiency and broad bandwidth. Waveguide crossings are essential circuit components, allowing for wave routing over shorter paths to increase circuit density. However, the simple intersection of two orthogonal effective-medium-clad waveguides results in terahertz wave scattering, leading to relatively high cross talk. In this work, a low-loss, 40% fractional bandwidth crossing utilizing Maxwell-Garnet effective-medium theory and wavefront planarization techniques is proposed. This monolithic structure is fabricated on a single high-resistivity float-zone silicon wafer using a deep reactive ion etching process with a modest 4.4 mm diameter (4.03λ0) structure footprint. Experimentally verified results show low insertion loss, less than 1 dB, and average cross talk level of -39dB for both E11x and E11y operating modes, over 220-330 GHz with a 40% fractional bandwidth. This waveguide crossing can be foreseen as a useful routing component for terahertz all-silicon integrated circuits. The proposed techniques are applicable to other dielectric waveguide platforms at infrared and optical frequencies.

Effective-medium-cladded dielectric waveguides for terahertz waves.

Terahertz integrated platforms with high efficiency are crucial in a broad range of applications including terahertz communications, radar, imaging and sensing. One key enabling technology is wideband interconnection. This work proposes substrate-less all-dielectric waveguides defined by an effective medium with a subwavelength hole array. These self-supporting structures are built solely into a single silicon wafer to minimize significant absorption in metals and dielectrics at terahertz frequencies. In a stark contrast to photonic crystal waveguides, the guiding mechanism is not based on a photonic bandgap but total internal reflections The waveguides are discussed in the context of terahertz communications that imposes stringent demands on performance. Experimental results show that the realized waveguides can cover the entire 260-400 GHz with single dominant modes in both orthogonal polarizations and an average measured attenuation around 0.05 dB/cm. Limited by the measurement setup, the maximum error-free data rate up to 30 Gbit/s is experimentally achieved at 335 GHz on a 3-cm waveguide. We further demonstrate the transmission of uncompressed 4K-resolution video across this waveguide. This waveguide platform promises integration of diverse active and passive components. Thus, we can foresee it as a potential candidate for the future terahertz integrated circuits, in analogy to photonic integrated circuits at optical frequencies. The proposed concept can potentially benefit integrated optics at large.

Hydroxamic Acid Derivatives of ß-Carboline/Hydroxycinnamic Acid Hybrids Inducing Apoptosis and Autophagy through the PI3K/Akt/mTOR Pathways.

Naturally occurring ß-carbolines are known to have antitumor activities but with limited effectiveness. In order to improve their efficacy, a series of new hydroxamic-acid-containing ß-carbolines connected via a hydroxycinnamic acid moitey (12a-f) were developed to incorporate histone deacetylase (HDAC) inhibition for possible synergistic effects. When evaluated in in vitro assays, most of the analogues showed significant antitumor activities against four human cancer cells. In particular, 12b showed the highest cytotoxic potency of the series, including drug-resistant Bel7402 cells, but had minimal effect on normal hepatic LO2 cells. These compounds also showed excellent inhibitory effects against HDAC1/6, which appear to contribute greatly to their antiproliferative properties. Compound 12b enhanced the acetylation levels of histone H3 and α-tubulin and induced greater cancer cell apoptosis than the FDA-approved HDAC inhibitor SAHA by regulating expression of apoptotic proteins Bax, Bcl-2, and caspase 3. Importantly, 12b also induced a significant amount of autophagic flux activity in Bel7402 cells by increasing the expression of Beclin-1 and LC3-II proteins and decreasing that of LC3-I and p62. Finally, 12b significantly inhibited PI3K/Akt/mTOR signaling, an important cell-growth-promoting pathway aberrantly activated in many cancers. Together, the results suggest that these hydroxamic-acid-containing ß-carboline derivatives may be new leads for the discovery of agents for the treatment of human carcinoma cancers.

Overexpression of Tripartite Motif Conaining 55 (TRIM55) Inhibits Migration and Invasion of Hepatocellular Carcinoma (HCC) Cells via Epithelial-Mesenchymal Transition and Matrix Metalloproteinase-2 (MMP2).

BACKGROUND Tripartite motif containing 55 (TRIM55) plays a regulatory role in assembly of sarcomeres, but few studies have assessed its function in hepatocellular carcinoma (HCC). MATERIAL AND METHODS Immunohistochemistry (IHC) was used to detect expression of TRIM55 in tissues samples of HCC patients. Transwell assay was used to study migration and invasion ability of HCC cells. Western blot and immunofluorescence (IF) were used to analyze mechanism of TRIM55 in cell migration and invasion. RESULTS We found TRIM55 was downregulated in HCC tissues and was associated with prognosis of HCC patients. Cox regression analysis showed that TRIM55 was an independent risk factor of prognosis of HCC patients. Overexpression of TRIM55 was associated with lower cell migration and invasion ability, and it led to high expression of E-cadherin and low expression of Vimentin and MMP2. CONCLUSIONS Our study found TRIM55 is an independent factor affecting the prognosis of HCC patients, and overexpression of TRIM55 inhibits migration and invasion of HCC cells through epithelial-mesenchymal transition and MMP2.

Stimuli-Responsive Properties of Aggregation-Induced-Emission Compounds Containing a 9,10-Distyrylanthracene Moiety.

Two 9,10-distyrylanthracene-based luminophores exhibiting aggregation-induced emission and stimuli-responsive properties were synthesized. Seven- or five-color luminescence switching based on a single organic molecule was achieved for the first time. These phase transitions can be induced by physical stimuli such as grinding by mortar and pestle, heating, and exposure to the vapors of organic solvents. Moreover, a strategy for the design of new mechanoresponsive materials with π-conjugated luminophores is proposed.

Variation in nurse self-reported practice of managing chest tubes: A cross-sectional study.

AIMS AND OBJECTIVES: To reveal nurses' self-reported practice of managing chest tubes and to define decision-makers for these practices. BACKGROUND: No consensus exists regarding ideal chest-tube management strategy, and there are wide variations of practice based on local policies and individual preferences, rather than standardised evidence-based protocols. DESIGN: This article describes a cross-sectional study. METHODS: Questionnaires were emailed to 31 hospitals in Tianjin, and the sample consisted of 296 clinical nurses whose work included nursing management of chest drains. The questionnaire, which was prepared by the authors of this research, consisted of three sections, including a total of 22 questions that asked for demographic information, answers regarding nursing management that reflected the practice they actually performed and who the decision-makers were regarding eight chest-drain management procedures. McNemar's test was used to analyse the data. RESULTS: The results indicated that most respondents thought that it was necessary to manipulate chest tubes to remove clots impeding unobstructed drainage (91.2%). Most respondents indicated that dressings would be changed when the dressing was dysfunctional. At the same time, more than half of respondents approved of changing dressings routinely, and the frequency of changing dressings varied. When drainage was employed for pleural effusion and for a pneumothorax, 64.6% and 94.5% of respondents, respectively, considered that underwater seal-drainage bottles should be changed routinely, and the frequency of changing bottles both varied. The results indicated that nurses were the primary decision-makers in the replacement of chest tubes, manipulation of chest tubes and monitoring of drainage fluid. CONCLUSIONS: There was considerable variation in respondents' self-reported clinical nursing practice regarding management of chest drains. The rationale on which respondents' practices were based also varied greatly. This study indicated that nurses were the primary decision-makers for three of eight procedures regarding management of chest drains, which reflects that clinical nurses' decision-making power regarding management of chest drains was weak. RELEVANCE TO CLINICAL PRACTICE: This study describes the nurse-reported practices of Chinese nurses from Tianjin, including changing and selecting dressing types, manipulating chest tubes, clamping drains and replacing drainage bottles, and the study defines who the decision-makers were for these interventions. By focusing on nurses' self-report of behaviours in managing chest drains (actual nursing practice vs. nursing knowledge), this article also relates the literature to the research findings and denotes the gaps in knowledge for future research.

Synergistic induction of apoptosis in A549 cells by dihydroartemisinin and gemcitabine.

This report is designed to study the ability of the combined treatment with gemcitabine (Gem) and dihydroartemisinin (DHA) to induce apoptosis in a non-small-cell lung cancer cell line (A549 cells). This combination treatment synergistically inhibited cell growth by inducing apoptosis, and this synergistic action was not associated with reactive oxygen species (ROS). Although either Gem or DHA induced a significant increase in ROS generation, the combination treatment did not further enhance ROS level. Compared with single drugs, the combination treatment significantly potentiated Bak activation, loss of mitochondrial membrane potential, caspase-9 and -3 activation, indicating the important role of the Bak-mediated intrinsic apoptosis pathway in the synergistic action, which was further verified by the significant prevention of the cytotoxicity of the combination treatment by inhibiting one of caspase-9, -3 and Bcl-xL or silencing Bak. In addition, the combination treatment also synergistically activated caspase-8, and inhibition of Fas and caspase-8 presented significant prevention on the cytotoxicity of the combination treatment, indicating that the Fas-caspase-8-mediated extrinsic apoptosis pathway partially participated in the synergistic action. Collectively, the present study demonstrates a strong synergistic action of the combined treatment with Gem and DHA in inducing apoptosis of A549 cells via both the Bak-mediated intrinsic pathway and the Fas-caspase-8-mediated extrinsic pathway.

Reporting and methodological quality of systematic reviews or meta-analyses in nursing field in China.

The aim of this paper was to evaluate reporting and methodological quality of systematic reviews or meta-analyses in the nursing field in China. Over the last decade, evidence-based nursing has been gradually known and accepted by nurses in China, and the number of systematic reviews or meta-analyses of nursing flied has steadily increased, but the quality of these reviews is unsatisfactory. The Chinese Journal Full-Text Database, the Chinese Biomedicine Literature Database and the Wanfang Database were searched for systematic reviews or meta-analyses in the nursing field, from inception through December 2011. The Preferred Reporting Items of Systematic Reviews and Meta-analyses and the Assessment of Multiple Systematic Reviews checklists were used to assess reporting characteristics and methodological quality, respectively. A total of 63 systematic reviews or meta-analyses were identified. The deficiencies of methodological quality were mainly in literature searches, heterogeneity handling, recognition and assessment of publication bias. In addition, the deficiencies of reporting characteristics were reflected in incomplete reporting of literature search, quality assessment, risk of bias and results. Focusing on improving the quality of reporting and methodological quality of systematic reviews or meta-analyses in the nursing field in China is urgently needed.

Inside-Out Rational Design of Ornithine Cyclodeaminase RlOCD from Rhizobium leguminosarum by a Multiregion Synergy Strategy for Efficient Synthesis of l-Pipecolic Acid.

Lysine cyclodeaminase (LCD)-mediated synthesis of l-pipecolic acid (l-PA) from l-lysine (l-Lys) is a promising approach. However, only one LCD has been reported, and its inadequate activity limits industrial applications. To address this problem, a substrate analogue-guided enzyme mining strategy was employed. A novel ornithine cyclodeaminase (OCD) from Rhizobium leguminosarum (RlOCD) was identified in combination with directed macrogenomic approaches. RlOCD displayed a conversion rate of 28% at a substrate loading as high as 1000 mM. A multiregion synergy strategy consisting of pocket reshaping, dynamical cross-correlation matrix-guided coevolutionary design, and surface modification was used to design RlOCD from the inside-out. A quadruple mutant (V93C/L119C/I170T/R90L) designated Mu4 with significantly increased activity was obtained, which showed a 28.46-fold increase in the catalytic efficiency. The conversion of Mu4 was 91% within 10 h at 1000 mM (146.19 g L-1) loading. The space-time yield of 282.1 g L-1 d-1 is the highest level ever reported. Molecular dynamics simulations and interaction analyses revealed that efficient pocket expansion and unique conformational rearrangements increased the affinity for the substrate, resulting in a more catalytically active conformation. This study expands the toolbox for the production of l-PA and demonstrates the effectiveness and potential of Mu4 for its production.

[Development and exploration of the national first-class undergraduate course in "Enzyme Engineering"].

The biotechnology industry is a strategic emerging industry in our country, holding a crucial position in the national economy. The training of innovative high-quality professionals carries immense significance. As the cornerstone course in biotechnology, "Enzyme Engineering" directly impacts the students' caliber and industry development. This course aims to address pertinent issues present in the current curriculum delivery, such as inadequately optimized content, excessive dependency on textbooks, and reliance on monotonous teaching methods. By adjusting the course outline, updating the case material repository, and engaging students' enthusiasm, we developed a three-dimensional approach to instruct. This approach included a blend of online and offline components, interactive teaching through the flipped classroom methodology, heuristic teaching using problem-based learning (PBL) mode, and topic teaching via case studies. We also improved the assessment mechanism to stimulate students' enthusiasm for learning nurture their innovation capabilities. Our objective was to foster high-quality professionals with a robust foundation and practical expertise. Through teaching exploration and practice, we have witnessed significant improvement in both teaching efficacy and students' engineering practice and innovation abilities.

LHPP in Glutamatergic Neurons of the Ventral Hippocampus Mediates Depression-like Behavior by Dephosphorylating CaMKIIα and ERK.

BACKGROUND: LHPP was recently shown to be a risk gene for major depressive disorder. LHPP has been proven to dephosphorylate the residues of histidine, serine, threonine, and tyrosine. However, much remains unknown about how LHPP contributes to depression. METHODS: In the current study, we addressed this issue by integrating approaches of genetics, molecular biology, behavioral testing, and electrophysiology. RESULTS: We found that levels of LHPP were upregulated in glutamatergic neurons of the ventral hippocampus in mice that displayed stress-induced depression-like behaviors. Knockout of LHPP in glutamatergic neurons of the brain improved the spontaneous activity of LHPPflox/flox·CaMKIIαCre+ (conditional knockout) mice. Adeno-associated virus-mediated LHPP knockdown in the ventral hippocampus enhanced resistance against chronic social defeat stress in mice. Manipulations of LHPP levels impacted the density of dendritic spines and excitability of CA1 pyramidal neurons by mediating the expressions of BDNF (brain-derived neurotrophic factor) and PSD95 via the modulation of the dephosphorylation of CaMKIIα and ERK. Notably, compared with wild-type LHPP, human mutant LHPP (E56K, S57L) significantly increased the activity of the CaMKIIα/ERK-BDNF/PSD95 signaling pathway. Finally, esketamine, not fluoxetine, markedly alleviated the LHPP upregulation-induced depression-like behaviors. CONCLUSIONS: These findings provide evidence that LHPP contributes to the pathogenesis of depression via threonine and serine hydrolases, thereby identifying LHPP as a potential therapeutic target in treating patients with major depressive disorder.

Impact of the Interruption Duration on Photoluminescence Properties of MOCVD-Grown GaAsP/InAlGaAs Quantum Well Structures.

The growth interruption technology is introduced to the growth of GaAsP/InAlGaAs quantum well (QW) structure using metal-organic chemical vapor deposition (MOCVD). The effect of growth interruption time (GIT) on the crystalline quality and optical properties are investigated. The two distinctive emission peaks are the transition recombination between the electron level of conduction band and the light and heavy hole level of valence band in the photoluminescence (PL) at room temperature. The PL peaks present a redshift and merge together with the increasing GIT, which is attributed to the QW energy level shift caused by the increase in arsenic concentrations in GaAsP QW, the diversified thickness of QW and the variations of indium components in the InAlGaAs barrier layer. The Gaussian deconvolution parameters in temperature-dependent PL (TDPL) show that the GaAsP/InAlGaAs QW with a GIT of 6 s has a 565.74 meV activation energy, enhancing the carrier confinement in QW and the PL intensity, while the 6 s-GIT GaAsP QW has the increasing interface roughness and the non-radiative centers at the InGaAsP intermediate layer, leading to a spectral broadening. The QW with 10 s-GIT exhibits a small full width at half maximum (FWHM) with the various temperature, indicating reduced interface roughness and excellent crystal quality. An increase in GIT may be suitable for optimizing the optical properties of GaAsP/InAlGaAs QW.

Dual-responsive two-photon probe for specific lipid droplets near-infrared fluorescence imaging in the brain of epileptic mice.

Abnormal lipid metabolism in glial cells is a key pathological feature of epilepsy. The identification of lipid droplets (LDs) is essential for investigating lipid metabolism, disease progression, and potential therapeutic interventions. Two-photon imaging technology enables real-time visualization of the spatial distribution and temporal dynamics of LDs in epilepsy models. In this study, we developed a novel two-photon excited dual-responsive near-infrared fluorescent probe, CabA, based on viscosity and polarity, to monitor dynamic changes in LDs. The fluorescence of CabA at 670 nm exhibits a significant increase in response to low polarity and high viscosity due to the twisted intramolecular charge transfer and intramolecular charge transfer mechanisms. The LDs-targeting capability of CabA at the cellular level and the process of LDs generation between neurons and astrocytes during the pathological advancement of epilepsy have been validated. In situ synchronous imaging experiments in epileptic and normal mice using CabA revealed abnormal LDs accumulation in the brain during seizures. Two-photon fluorescence imaging further demonstrated LDs accumulation in the brains of epileptic mice at a penetration depth of 100 µm. This study offers a valuable tool for enhancing the understanding of LDs in physiological and pathological processes, potentially aiding in the early diagnosis of epilepsy.

Solidification/stabilization pre-treatment coupled with landfill disposal of heavy metals in MSWI fly ash in China: A systematic review.

The growth in municipal solid waste incineration (MSWI) has resulted in a substantial rise in the production of fly ash in China. It is anticipated that during the "14th Five-Year Plan", the accumulated amount of fly ash stocked and disposed of at landfills will surpass 100 million tons. With the development of the economy and the implementation of garbage classification relevant policies, the pollution characteristics of heavy metal change in spatiotemporal distribution. Solidification/stabilization (S/S) pre-treatment coupled with landfill disposal is the mainstream method for fly ash. This study provides a systematic overview and comparison of the current application status and research on the mechanism of S/S technology, and the long-term stability of solidified/stabilized fly ash is a crucial factor in controlling the risks of landfills. Subsequently, it examines the influencing factors and mechanisms associated with heavy metals leaching under different environmental scenarios (meteorological factors, leachate and acid rain erosion, and carbonation, etc.), and concludes that single stabilization technology is difficult to meet long-term landfill requirements. Finally, the limits of heavy metal leaching toxicity evaluation methods and landfilled fly ash supervision were discussed, and relevant suggestions for future development were proposed. This study can provide theoretical instruction and technical support for the risk control of potential environmental risks of heavy metals in solidified/stabilized fly ash from landfills in China.

Up-regulation of RAN by MYBL2 maintains osteosarcoma cancer stem-like cells population during heterogeneous tumor generation.

Intratumor heterogeneity is one of the major features of cancers, leading to aggressive disease and treatment failure. Cancer stem-like cells (CSCs) are believed to give rise to the heterogeneous cell types within tumors. Hence, understanding the regulatory mechanism underlying the recurrence process of heterogeneous tumor by CSCs could facilitate the development of CSC-targeted therapies. Here, utilizing single-cell transcriptomics, we present the molecular profile of osteosarcoma CSCs-derived heterogeneous tumors consisting of CSC clusters, osteoprogenitor and differentiated cell types, such as pre-osteoblasts, osteoblasts and chondroblasts. Furthermore, by constructing the comprehensive map of modulated genes during CSCs self-renewal and differentiation, we identify RAN exhibiting specific peak expression in osteosarcoma CSCs clusters which is transcriptionally up-regulated by MYBL2. Functionality, MYBL2-RAN pathway promotes the CSCs self-renewal by enhancing the nuclear accumulation of MYC protein, which in turn boosts the overexpression of RAN as a positive feedback. Importantly, blockage of MYBL2-RAN pathway sensitizes CSCs to cisplatin treatment and synergistically enhanced the cisplatin-induced cytotoxicity. Both MYBL2 and RAN are highly expressed in clinical osteosarcoma tissues which indicate poor prognosis. Collectively, our study provides advanced insights into the regeneration process of heterogeneous tumor originating from CSCs and highlights the MYBL2-RAN pathway as a promising target for CSC-based therapy in osteosarcoma.

Artemisinin induces A549 cell apoptosis dominantly via a reactive oxygen species-mediated amplification activation loop among caspase-9, -8 and -3.

This report is designed to explore the roles of caspase-8, -9 and -3 in artemisinin (ARTE)-induced apoptosis in non-small cell lung cancer cells (A549 cells). ARTE induced reactive oxygen species (ROS)-mediated apoptosis in dose- and time-dependent fashion. Although ARTE treatment did not induce Bid cleavage and significant loss of mitochondrial membrane potential, it induced release of Smac and AIF but not cytochrome c from mitochondria, and silencing of Bak but not Bax significantly prevented ARTE-induced cytotoxicity. Moreover, ARTE treatment induced ROS-dependent activation of caspase-9, -8 and -3. Of the utmost importance, silencing or inhibiting any one of caspase-8, -9 and -3 almost completely prevented ARTE-induced activation of all the three caspases and remarkably abrogated the cytotoxicity of ARTE, suggesting that ARTE triggered an amplification activation loop among caspase-9, -8 and -3. Collectively, our data demonstrate that ARTE induces a ROS-mediated amplification activation loop among caspase-9, -8 and -3 to dominantly mediate the apoptosis of A549 cells.

Targeting SIK3 to modulate hippocampal synaptic plasticity and cognitive function by regulating the transcription of HDAC4 in a mouse model of Alzheimer's disease.

Cognitive deterioration and memory decline associated with the progression of Alzheimer's disease (AD) primarily results from synaptic failure. However, current understanding of the upstream regulatory mechanisms controlling synaptic plasticity remains limited. Salt-inducible kinase 3 (SIK3) is central to the signal pathway and is involved in neuronal regulation of sleep duration in mice. We speculated that the SIK3 cascade signaling pathway might contribute to the pathogenesis of AD. Thus, the present study employed AD transgenic mouse models, Morris Water Maze, virus-mediated gene transfer, electrophysiology, co-immunoprecipitation, western blotting, quantitative polymerase chain reaction, immunofluorescence, ChIP-qPCR, Golgi-Cox staining and dendritic spine analysis to investigate this connection. Our results revealed that SIK3 mRNA/protein expression was significantly reduced in middle-aged AD transgenic mouse models and AD patients. Conditional deletion of SIK3 gene in dorsal hippocampal neurons of 5×FAD mice further accelerated cognitive deterioration and impaired synaptic plasticity. In hippocampal neuronal cultures, SIK3 formed a complex with HDAC4, directly phosphorylated HDAC4 and regulated its nuclear cytoplasmic shuttle. Overexpression of SIK3 could facilitate the expression of synaptic plasticity-related genes by directly repressing mef2c or involving the recruitment of histone deacetylase to promoter regions of target genes through regulation of p-HDAC4, and vice versa. Moreover, up-regulation of SLP-S, the truncated fragment of SIK3, in dorsal hippocampal neurons, restored the synaptic plasticity and alleviates the cognitive impairment in 5×FAD mice. Collectively, these findings revealed a novel and important role of SIK3-HDAC4 regulation of synaptic plasticity and propose a new target for therapeutic approaches of cognitive deficits associated with AD.

HnRNPK is involved in stress-induced depression-like behavior via ERK-BDNF pathway in mice.

As a ubiquitous RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) interacts with numerous nucleic acids and proteins and is involved in various cellular functions. Available literature indicates that it can regulate dendritic spine density through the extracellular signal-regulating kinase (ERK) - brain-derived neurotrophic factor (BDNF) pathway, which is crucial to retain the synaptic plasticity in patients with major depressive disorder (MDD) and mouse depression models. However, ERK upstream regulatory kinase has not been fully elucidated. Furthermore, it remains unexplored whether hnRNPK may impact the depressive condition via the ERK pathway. The present study addressed this issue by integrating approaches of genetics, molecular biology, behavioral testing. We found that hnRNPK in the brain was mainly distributed in the hippocampal neurons; that it was significantly downregulated in mice that displayed stress-induced depression-like behaviors; and that the level of hnRNPK markedly decreased in MDD patients from the GEO database. Further in vivo and in vitro analyses revealed that the changes in the expressions of BDNF and PSD95 and in the phosphorylation of ERK (Thr202/Tyr204) paralleled the variation of hnRNPK levels in the ventral hippocampal neurons in mice with depression-like behaviors. Finally, esketamine treatment significantly increased the level of hnRNPK in mice. These findings evidence that hnRNPK involved in the pathogenesis of depression via the ERK-BDNF pathway, pinpointing hnRNPK as a potential therapeutic target in treating MDD patients.