The influence of maternal and paternal parenting on adolescent brain structure.

BACKGROUND: Adolescents raised in families with different maternal and paternal parenting combinations exhibit variations in neurocognition and psychopathology; however, whether neural differences exist remains unexplored. This study used a longitudinal twin sample to delineate how different parenting combinations influence adolescent brain structure and to elucidate the genetic contribution. METHODS: A cohort of 216 twins participated in parenting assessments during early adolescence and underwent MRI scanning during middle adolescence. We utilized latent profile analysis to distinguish between various maternal and paternal parenting profiles and subsequently investigated their influences on brain anatomy. Biometric analysis was applied to assess the genetic influences on brain structure, and associations with internalizing symptoms were explored. RESULTS: In early adolescence, four parenting profiles emerged characterized by levels of harshness and hostility in one or both parents. Compared to adolescents in "catparent" families (low harshness/hostility in both parents), those raised in "tigermom" families (harsh/hostile mother only) exhibited smaller nucleus accumbens volume and larger temporal cortex surface area; those in "tigerdad" families demonstrated larger thalamus volumes; those in "tigerparent" families displayed smaller volumes in the mid-anterior corpus callosum. Genetic risk factors contributed significantly to the observed brain structural heterogeneity and internalizing symptoms. However, the influences of parenting profiles and brain structure on internalizing symptoms were not significant. CONCLUSIONS: The findings underscore distinct brain structural features linked to maternal and paternal parenting combinations, particularly in terms of subcortical volume and cortical surface area. This study suggests an interdependent role of maternal and paternal parenting in shaping adolescent neurodevelopment.

Methylation modifications in tRNA and associated disorders: Current research and potential therapeutic targets.

High-throughput sequencing has sparked increased research interest in RNA modifications, particularly tRNA methylation, and its connection to various diseases. However, the precise mechanisms underpinning the development of these diseases remain largely elusive. This review sheds light on the roles of several tRNA methylations (m1A, m3C, m5C, m1G, m2G, m7G, m5U, and Nm) in diverse biological functions, including metabolic processing, stability, protein interactions, and mitochondrial activities. It further outlines diseases linked to aberrant tRNA modifications, related enzymes, and potential underlying mechanisms. Moreover, disruptions in tRNA regulation and abnormalities in tRNA-derived small RNAs (tsRNAs) contribute to disease pathogenesis, highlighting their potential as biomarkers for disease diagnosis. The review also delves into the exploration of drugs development targeting tRNA methylation enzymes, emphasizing the therapeutic prospects of modulating these processes. Continued research is imperative for a comprehensive comprehension and integration of these molecular mechanisms in disease diagnosis and treatment.

Fabrication of Ceramic Microchannels with Periodic Corrugated Microstructures as Catalyst Support for Hydrogen Production via Diamond Wire Sawing.

Hydrogen energy is the clean energy with the most potential in the 21st century. The microchannel reactor for methanol steam reforming (MSR) is one of the effective ways to obtain hydrogen. Ceramic materials have the advantages of high temperature resistance, corrosion resistance, and high mechanical strength, and are ideal materials for preparing the catalyst support in microchannel reactors. However, the structure of ceramic materials is hard and brittle, and the feature size of microchannel is generally not more than 1 mm, which is difficult to process using traditional processing methods. Diamond wire saw processing technology is mainly used in the slicing of hard and brittle materials such as sapphire and silicon. In this paper, a microchannel with a periodic corrugated microstructure was fabricated on a ceramic plate using diamond wire sawing, and then as a catalyst support when used in a microreactor for MSR hydrogen production. The effects of wire speed and feed speed on the amplitude and period size of the periodic corrugated microstructure were studied using a single-factor experiment. The microchannel surface morphology was observed via SEM and a 3D confocal laser microscope under different processing parameters. The microchannel samples obtained under different processing parameters were supported by a multiple impregnation method. The loading strength of the catalyst was tested via a strong wind purge experiment. The experimental results show that the periodic corrugated microstructure can significantly enhance the load strength of the catalyst. The microchannel catalyst support with the periodic corrugated microstructure was put into the microreactor for a hydrogen production experiment, and a good hydrogen production effect was obtained. The experimental results have a positive guiding effect on promoting ceramic materials as the microchannel catalyst support for the development of hydrogen energy.

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

CRISPR/Cas12a-Powered Amplification-Free RNA Diagnostics by Integrating T7 Exonuclease-Assisted Target Recycling and Split G-Quadruplex Catalytic Signal Output.

Rapid and sensitive RNA detection is of great value in diverse areas, ranging from biomedical research to clinical diagnostics. Existing methods for RNA detection often rely on reverse transcription (RT) and DNA amplification or involve a time-consuming procedure and poor sensitivity. Herein, we proposed a CRISPR/Cas12a-enabled amplification-free assay for rapid, specific, and sensitive RNA diagnostics. This assay, which we termed T7/G4-CRISPR, involved the use of a T7-powered nucleic acid circuit to convert a single RNA target into numerous DNA activators via toehold-mediated strand displacement reaction and T7 exonuclease-mediated target recycling amplification, followed by activating Cas12a trans-cleavage of the linker strands inhibiting split G-Quadruplex (G4) assembly, thereby inducing fluorescence attenuation proportion to the input RNA target. We first performed step-by-step validation of the entire assay process and optimized the reaction parameters. Using the optimal conditions, T7/G4-CRISPR was capable of detecting as low as 3.6 pM target RNA, obtaining ∼100-fold improvement in sensitivity compared with the most direct Cas12a assays. Meanwhile, its excellent specificity could discriminate single nucleotide variants adjacent to the toehold region and allow species-specific pathogen identification. Furthermore, we applied it for analyzing bacterial 16S rRNA in 40 clinical urine samples, exhibiting a sensitivity of 90% and a specificity of 100% when validated by RT-quantitative PCR. Therefore, we envision that T7/G4-CRISPR will serve as a promising RNA sensing approach to expand the toolbox of CRISPR-based diagnostics.

Hybrid transmission of PS-GS4QAM and QPSK data in the form of a PS-16QAM mm-wave signal enabled by optical asymmetrical dual-SSB modulation.

The independent optical dual-single-sideband (dual-SSB) signal generation and detection can be achieved by an optical in-phase/quadrature (I/Q) modulator and one single photodiode (PD). The dual-SSB signal is able to carry two different information. After PD detection, the optical dual-SSB signal can be converted into an electrical millimeter-wave (mm-wave) signal. Therefore, the optical dual-SSB signal generation and detection technique can be employed in the radio-over-fiber (RoF) system to achieve higher system spectral efficiency and reduce system architecture complexity. However, the I/Q modulator's nonideal property results in the amplitude imbalance of the optical dual-SSB signal, and then the crosstalk can occur. Moreover, after PD detection, the generated mm-wave signal based on the optical dual-SSB modulation has a relatively low signal-to-noise ratio (SNR), which restricts the system performance. In this paper, we propose an optical asymmetrical dual-SSB signal generation and detection scheme based on the probabilistic shaping (PS) technology, to decrease the influence of the optical dual-SSB signal's amplitude imbalance and to enhance the system performance in the scenario of the limited SNR. The dual-SSB in our scheme is composed of the left sideband (LSB) in probabilistic-shaping geometric-shaping 4-ary quadrature amplitude modulation (PS-GS4QAM) format and the right sideband (RSB) in quadrature phase-shift keying (QPSK) format. The transmitter digital signal processing (DSP) generates a dual-SSB signal to drive the optical I/Q modulator. The I/Q modulator implements an electrical-to-optical conversion and generates an optical dual-SSB signal. After PD detection, the optical dual-SSB signal is converted into a PS-16QAM mm-wave signal. In our simulation, compared with the normal 16QAM scenario, the PS-16QAM scenario exhibits a ∼1.2 dB receiver sensitivity improvement at the hard-decision forward error correction (HD-FEC) threshold of 3.8×10-3. Therefore, in our experiment, based on the PS technology, we design a dual-SSB signal including a 5 Gbaud LSB-PS-GS4QAM at -15 GHz and a 5 Gbaud RSB-QPSK at 20 GHz. After 5 km standard single-mode fiber (SSMF) transmission and PD detection, the dual-SSB signal is converted into a 5 Gbaud PS-16QAM mm-wave signal at 35 GHz. Then, the generated PS-16QAM signal is sent into a 1.2 m single-input-single-output (SISO) wireless link. In the DSP at the receiver end, the dual-SSB signal can be recovered from the mm-wave signal, and the PS-GS4QAM and QPSK data carried by the dual-SSB signal can be separated. The bit error rates (BERs) of the LSB-PS-GS4QAM and the RSB-QPSK in our experiment can be below the HD-FEC threshold of 3.8×10-3. The results demonstrate that our scheme can tolerate the I/Q modulator's nonideal property and performs well in the scenario of a relatively low SNR.

Simultaneous wireless mm-wave transmission of both SC-modulated and OFDM-modulated high-order QAM signals enabled by bandpass delta-sigma modulation.

The application of dual vector millimeter-wave (mm-wave) signals in radio-over-fiber (RoF) systems represents a significant opportunity to enhance spectrum efficiency, transmission capacity, and access flexibility. In addition, facing the increasingly intricate application scenarios, the comprehensive exploitation of high-order quadrature-amplitude-modulation (QAM) signals with hybrid single-carrier (SC) and orthogonal-frequency-division-multiplexing (OFDM) modulation is also vital to rich systematic connotation. Based on bandpass delta-sigma modulation (BP-DSM) and heterodyne detection, we propose what we believe to be a novel scheme for the simultaneous wireless mm-wave transmission of both SC-modulated and OFDM-modulated high-order QAM signals. The innovation lies in the modulation-agnostic nature, accommodating both SC-modulated and OFDM-modulated vector radio-frequency (RF) signals. The BP-DSM is utilized to digitize two independent SC-modulated and OFDM-modulated high-order QAM signals into relatively simple sequences at the transmitter side. With the aid of an optical I/Q modulator, we can integrate both signals after BP-DSM to generate the desired optical quadrature-phase-shift keying (QPSK) signal carrying both information of two original high-order QAM signals. Facilitated by heterodyne detection and a single photodetector (PD), our scheme attains prowess in the detection of both SC-modulated and OFDM-modulated high-order signals. Based on our proposed scheme, we experimentally demonstrate the simultaneous wireless mm-wave transmission of both SC-modulated and OFDM-modulated 512QAM signals at 30-GHz mm-wave band, demonstrating bit-error-rates (BERs) below the hard decision forward error correction (HD-FEC) threshold of 3.8 × 10-3 after transmission over 10-km single-mode fiber (SMF) link and 1-m wireless link. In addition, we further investigate the performance impact between SC-modulated and OFDM-modulated high-order QAM signals, and experiment results indicate that the impact is virtually negligible. Moreover, the performance of the generated QPSK mm-wave signal is transparent to the QAM modulation formats of both SC-modulated and OFDM-modulated signals in our proposed scheme.

Breakfast skipping and risk of all-cause, cardiovascular and cancer mortality among adults: a systematic review and meta-analysis of prospective cohort studies.

Background: Numerous studies reported inconsistent association between breakfast skipping and all-cause, cardiovascular disease (CVD) and cancer mortality. Therefore, we conducted a systematic review and meta-analysis to elucidate these associations. Methods: PubMed, Embase, and Web of Science databases were searched up to July 2023 for prospective cohort studies that assessed the association between breakfast skipping and all-cause, CVD and cancer mortality in general adults. A random effect model was used to estimate the pooled hazard ratio (HR) and 95% confidence intervals (CIs), with subgroup analysis and sensitivity analysis performed. The Newcastle-Ottawa Scale (NOS) was used to assess the study and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: The final analysis included 9 cohort studies including 242 095 participants, with 6 studies for all-cause mortality, 4 studies for CVD mortality, and 2 studies for cancer mortality. Compared to regular breakfast consumption, skipping breakfast was associated with a higher risk of all-cause (HR: 1.27, 95% CI, 1.07-1.51, I2 = 77%), CVD (HR 1.28, 95% CI 1.10-1.50, I2 = 0), and cancer (HR: 1.34, 95% CI: 1.11-1.61, I2 = 0%) mortality. Sensitivity analysis revealed inconsistent results in all-cause and CVD mortality. Subgroup analysis showed significant association in studies with larger participants, longer follow-up, adjustments for energy intake, and high-quality articles. GRADE showed very low evidence for all-cause mortality and low evidence for CVD and cancer mortality. Conclusion: The findings underscore the importance of regular breakfast habits for health and longevity. However, these results require careful interpretation due to geographic limitations, potential heterogeneity, and instability.

pHLIP-fused PD-L1 engages avelumab to elicit NK cytotoxicity under acidic conditions.

Natural killer (NK) cells represent key player in immune surveillance to eliminate transformed or malignant cells. One of mechanisms of action of NK cells is antibody-dependent cell-mediated cytotoxicity (ADCC) by recognizing tumor antigens on the surface of cancer cells. However, the heterogeneity of tumor antigens and the scarcity of membrane surface targets significantly restrict this strategy. Recently, we constructed a new cargo by tethering a low pH insertion peptide (pHLIP) to the C terminus of the ectodomain of programed death ligand-1 (PD-L1) and demonstrated its ability to modulate immune responses. Herein, the potential application of PD-L1-pHLIP in cancer therapy was determined. pHLIP tethering had no effect on the binding capacity of PD-L1 protein to an anti-PD-L1 antibody (i.e. avelumab). Association of pHLIP rendered PD-L1 segment display on the surface of cellular membrane in the acidic buffer instead of the neutral solution. Importantly, plate-coated or beads-coupled PD-L1-pHLIP enable robust activation and expression of cytotoxic mediators of NK cells via engaging avelumab. Overall, this work provides proof of concept that recombinant PD-L1 protein decorated on the cellular membrane driven by pHLIP in combination with appropriate monoclonal antibody has potentials to elicit NK cytotoxicity, which may represent a novel and promising therapeutic avenue in cancer.

Development and characterization of an antibody that recognizes influenza virus N1 neuraminidases.

Influenza A viruses (IAVs) continue to pose a huge threat to public health, and their prevention and treatment remain major international issues. Neuraminidase (NA) is the second most abundant surface glycoprotein on influenza viruses, and antibodies to NA have been shown to be effective against influenza infection. In this study, we generated a monoclonal antibody (mAb), named FNA1, directed toward N1 NAs. FNA1 reacted with H1N1 and H5N1 NA, but failed to react with the NA proteins of H3N2 and H7N9. In vitro, FNA1 displayed potent antiviral activity that mediated both NA inhibition (NI) and blocking of pseudovirus release. Moreover, residues 219, 254, 358, and 388 in the NA protein were critical for FNA1 binding to H1N1 NA. However, further validation is necessary to confirm whether FNA1 mAb is indeed a good inhibitor against NA for application against H1N1 and H5N1 viruses.

In vitro modeling of recurrent Dermatofibrosarcoma Protuberans: Assessment of 5-aminolevulinic acid photodynamic therapy efficacy.

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. METHODS: This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. RESULTS: 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. CONCLUSIONS: The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence.

Dual high-order QAM-modulated mm-wave signal transmission in the Q-band enabled by simple IM/DD architecture and bandpass delta-sigma modulation.

The intensity-modulation (IM)/direct-detection (DD) systems have been proven effective and low-cost due to their simple system architecture. However, the Mach-Zehnder modulator (MZM) of the IM/DD systems only reserves its driving signal intensity. Therefore, the IM/DD systems are generally unable to transmit vector signals and have a restricted spectrum efficiency and channel capacity. Similarly, the radio-over-fiber (RoF) transmission systems based on IM/DD are limited by their simple architecture and generally cannot transmit high-order quadrature amplitude modulation (QAM) signals, which hinders the improvement of their spectrum efficiency. To address the challenges, we propose a novel, to the best of our knowledge, scheme to simultaneously transmit the dual independent high-order QAM-modulated millimeter-wave (mm-wave) signals in the RoF system with a simple IM/DD architecture, enabled by precoding-based optical carrier suppression (OCS) modulation and bandpass delta-sigma modulation (BP-DSM). The dual independent signals can carry different information, which increases channel capacity and improves spectrum efficiency and system flexibility. Based on our proposed scheme, we experimentally demonstrate the dual 512-QAM mm-wave signal transmission in the Q-band (33-50 GHz) under three different scenarios: 1) dual single-carrier (SC) signal transmission, 2) dual orthogonal-frequency-division-multiplexing (OFDM) signal transmission, and 3) hybrid SC and OFDM signal transmission. We achieve high-fidelity transmission of dual 512-QAM vector signals over a 5 km single-mode fiber (SMF) and a 1-m single-input single-output (SISO) wireless link operating in the Q-band, with the bit error rates (BERs) of all three scenarios below the hard decision forward error correction (HD-FEC) threshold of 3.8 × 10-3. To the best of our knowledge, this is the first time dual high-order QAM-modulated mm-wave signal transmission has been achieved in a RoF system with a simple IM/DD architecture.

Familial genetic and environmental transmission of depression: A multi-informant twin family study.

The phenomenon of familial clustering in depression is well established, yet the mechanisms by which depression is transmitted within families remain poorly understood. In the current study, we investigate the familial genetic and environmental transmission of depression by incorporating data from both adolescent twins and their parents. A total of 987 twin families were recruited from the Beijing Twin Study. Depression assessments were conducted for both adolescents and their parents. Twins' depression was assessed through reports from both the twins themselves and their parents, while parental depression was assessed by parental self-report. We employed a nuclear twin family model to examine genetic and environmental influences on adolescent depression. Our results, based on both self- and parent-report, demonstrate significant additive and dominant genetic influences on depression. We also found mild yet significant sibling environmental influences, while familial environmental influences were absent. Notably, parent-reported depression showed higher heritability but lower unique environmental influences compared with self-reported depression. These results highlight the important role of genetic transmission and sibling environmental transmission in explaining depression. Our study delineates the underlying mechanism of familial transmission in depression and can inform early treatments to halt transmission during adolescence.

SC and OFDM hybrid coherent optical transmission scheme based on 1-bit bandpass delta-sigma modulation.

High-order quadrature amplitude modulation (QAM) can effectively improve the capacity and spectral efficiency of coherent optical transmission systems. However, as the modulation order increases, the signal becomes less tolerant to noise and nonlinear effects during transmission, and the implementation cost also increases. We propose a single carrier (SC) and orthogonal frequency division multiplexing (OFDM) hybrid coherent optical transmission scheme based on a 1-bit bandpass (BP) delta-sigma modulation (DSM). The driving I-channel and Q-channel signals for the optical in-phase/quadrature (I/Q) modulator carry SC-modulated and OFDM-modulated transmitter data, respectively. Optical quadrature-phase-shift-keying (QPSK) modulation is realized by the 1-bit DSM quantizer and I/Q modulator, which can effectively suppress quantization noise and reduce the complexity of digital signal processing (DSP) and the performance requirements of optoelectronic devices. In addition, the hybrid transmission of SC and OFDM can balance the advantages of both to meet the variable channel conditions and complex application scenarios. High-fidelity transmission of SC 512QAM and OFDM 512QAM hybrid signals, in the form of a 60 Gbaud optical QPSK signal, over 60 km single-mode fiber-28 (SMF-28) is verified by offline experiments, and the bit error rates (BERs) of both SC 512QAM and OFDM 512QAM are below the hard-decision forward-error correction (HD-FEC) threshold of 3.8e-3.

Differentiation of Type 17 Mucosal-Associated Invariant T Cells in Circulation Contributes to the Severity of Sepsis.

Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and retinoic acid receptor-related orphan receptor γt in patients with sepsis. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA-sequencing analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in patients with sepsis. Cell-culture experiments demonstrated that phosphoinositide 3-kinase-LDHA signaling was required for retinoic acid receptor-related orphan receptor γt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 cells in sepsis. In summary, this study reveals a new role of circulating MAIT17 in promoting sepsis severity and suggests the phosphoinositide 3-kinase-LDHA signaling as a driving force in MAIT17 responses.

Ghrelin regulates the endoplasmic reticulum stress signalling pathway in gestational diabetes mellitus.

OBJECTIVE: We aimed to investigate the effects and mechanisms of the ghrelin-regulated endoplasmic reticulum stress (ERS) signalling pathway in gestational diabetes mellitus (GDM). METHODS: Pregnant female C57BL/6 mice were randomly divided into a normal group, GDM group (high-fat diet + STZ), GDM + ghrelin group (acyl ghrelin), and GDM + ghrelin + ghrelin inhibitor group ([D-lys3]-GHRP-6). We measured body weight, the intake of water and food, glucose, cholesterol, triglyceride and fasting insulin levels in each group. HE staining was used to observe the morphological changes in the pancreas. The TUNEL method was used to detect the apoptosis rate of islet cells. qPCR and Western boltting were performed to detect the relative expression levels of PERK, ATF6, IREIα, GRP78, CHOP and caspase-12, which are related to the ERS signalling pathway in the pancreas. Then, NIT-1 cells were cultured to verify whether ghrelin regulates ERS under high-glucose or tunicamycin conditions. RESULTS: Compared with the GDM group, the GDM + ghrelin group showed improved physical conditions and significantly decreased the fasting blood glucose, glucose tolerance, cholesterol, triglyceride and fasting insulin levels. Damaged islet areas were inhibited by ghrelin in the GDM group. The GDM + ghrelin group showed reduced ß-cell apoptosis compared to the GDM and GDM + ghrelin + ghrelin inhibitor groups. ERS-associated factors (PERK, ATF6, IREIα, GRP78, CHOP and caspase-12) mRNA and protein levels were obviously lower in the GDM + ghrelin group than in the GDM group, while expression levels were restored in the inhibitor group. Ghrelin treatment improved the high-glucose or tunicamycin-induced apoptosis, increased insulin levels and upregulation of GRP78, CHOP and caspase-12 in NIT-1 cells. CONCLUSION: Ghrelin suppressed ERS signalling and apoptosis in GDM mice and in NIT-1 cells. This study established a link between ghrelin and GDM, and the targeting of ERS with ghrelin represents a promising therapeutic strategy for GDM.

Dissolving Hyaluronic Acid-Based Microneedles to Transdermally Deliver Eugenol Combined with Photothermal Therapy for Acne Vulgaris Treatment.

A microneedle transdermal drug delivery system simultaneously avoids systemic toxicity of oral administration and low efficiency of traditional transdermal administration, which is of great significance for acne vulgaris therapy. Herein, eugenol-loaded hyaluronic acid-based dissolving microneedles (E@P-EO-HA MNs) with antibacterial and anti-inflammatory activities are developed for acne vulgaris therapy via eugenol transdermal delivery integrated with photothermal therapy. E@P-EO-HA MNs are pyramid-shaped with a sharp tip and a hollow cavity structure, which possess sufficient mechanical strength to penetrate the stratum corneum of the skin and achieve transdermal delivery, in addition to excellent in vivo biocompatibility. Significantly, E@P-EO-HA MNs show effective photothermal therapy to destroy sebaceous glands and achieve antibacterial activity against deep-seated Propionibacterium acnes (P. acnes) under near-infrared-light irradiation. Moreover, cavity-loaded eugenol is released from rapidly dissolved microneedle bodies to play a sustained antibacterial and anti-inflammatory therapy on the P. acnes infectious wound. E@P-EO-HA MNs based on a synergistic therapeutic strategy combining photothermal therapy and eugenol transdermal administration can significantly alleviate inflammatory response and ultimately facilitate the repair of acne vulgaris. Overall, E@P-EO-HA MNs are expected to be clinically applied as a functional minimally invasive transdermal delivery strategy for superficial skin diseases therapy in skin tissue engineering.

Unravelling the underlying mechanism of the reduction of aldehydes/ketones with metal borohydride in an aprotic solvent.

The reduction mechanism of aldehyde/ketones with M(BH4)n is not fully understood, even though the hydroboration mechanism of weak Lewis base borane complexes is known to involve a four-membered ring transition state. Herein, the reduction mechanism of M(BH4)n in aprotic solvents has been elucidated for a six-membered ring, in which hydride transfer to the C atom from the B atom, formation of an L·BH3 adduct, and disproportionation of (BH3(OR)-) borane are involved. The metal cations and solvents participate in and significantly influence the reaction procedure. We believe that this mechanistic study would provide a further reference for the application of M(BH4)n in organic reactions.

Comparative transcriptomic analysis delineates adaptation strategies of Rana kukunoris toward cold stress on the Qinghai-Tibet Plateau.

BACKGROUND: Cold hardiness is fundamental for amphibians to survive during the extremely cold winter on the Qinghai-Tibet plateau. Exploring the gene regulation mechanism of freezing-tolerant Rana kukunoris could help us to understand how the frogs survive in winter. RESULTS: Transcriptome of liver and muscle of R. kukunoris collected in hibernation and spring were assisted by single molecule real-time (SMRT) sequencing technology. A total of 10,062 unigenes of R. kukunoris were obtained, and 9,924 coding sequences (CDS) were successfully annotated. Our examination of the mRNA response to whole body freezing and recover in the frogs revealed key genes concerning underlying antifreeze proteins and cryoprotectants (glucose and urea). Functional pathway analyses revealed differential regulated pathways of ribosome, energy supply, and protein metabolism which displayed a freeze-induced response and damage recover. Genes related to energy supply in the muscle of winter frogs were up-regulated compared with the muscle of spring frogs. The liver of hibernating frogs maintained modest levels of protein synthesis in the winter. In contrast, the liver underwent intensive high levels of protein synthesis and lipid catabolism to produce substantial quantity of fresh proteins and energy in spring. Differences between hibernation and spring were smaller than that between tissues, yet the physiological traits of hibernation were nevertheless passed down to active state in spring. CONCLUSIONS: Based on our comparative transcriptomic analyses, we revealed the likely adaptive mechanisms of R. kukunoris. Ultimately, our study expands genetic resources for the freezing-tolerant frogs.

Dual vector millimeter-wave signal generation based on optical carrier suppression modulation and direct detection with one photodetector.

We propose a novel, to the best of our knowledge, scheme for dual vector millimeter-wave (mm-wave) signal generation and transmission, based on optical carrier suppression (OCS) modulation, precoding, and direct detection by a single-ended photodiode (PD). At the transmitter side, two independent vector radio frequency (RF) signals with precoding, generated via digital signal processing (DSP), are used to drive an in-phase/quadrature (I/Q) modulator operating at the optical OCS modulation mode to simultaneously generate two independent frequency-doubling optical vector mm-wave signals, which can reduce the bandwidth requirement of transmitter's components and enhance spectral efficiency. With the aid of the single-ended PD and subsequent DSP at the receiver side, two independent frequency-doubling vector mm-wave signals can be separated and demodulated without data error. Based on our proposed scheme, we experimentally demonstrate the generation, transmission, and detection of 2-Gbaud 30-GHz quadrature-phase-shift-keying (QPSK) and 2-Gbaud 46-GHz QPSK signals over 10-km single-mode fiber-28 (SMF-28) and 1-m wireless transmission. The results indicate that the bit-error ratio (BER) of the dual vector mm-wave signals can each reach the hard-decision forward-error-correction (HD-FEC) threshold of 3.8 × 10-3.