Genetic and immune identification and functional analysis of TRPM8 as a potential biomarker for pancreatic adenocarcinoma proliferation.

BACKGROUND: Pancreatic adenocarcinoma (PAAD), a member of highly lethal malignant tumors, has a poor outcome and extremely poor prognosis. The transient receptor potential (TRP) superfamily, a group of nonselective cation channels, is capable of influencing cellular functions by regulating calcium homeostasis. In addition, it has been shown that TRP channels can also affect various cellular phenotypes by regulating gene transcription levels and are involved in the development of a variety of malignant tumors. AIMS: In order to find new therapeutic targets and biomarkers to improve the clinical prognosis of pancreatic cancer, we performed genetic and immunological characterization of TRP channels in PAAD, as well as related functional and prognostic analyses. METHODS AND RESULTS: We investigated the expression, genetic alterations, methylation levels, and immune infiltration levels of TRP channels in PAAD, and further also analyzed the function of TRP channels in PAAD and their prognostic value for PAAD patients. Our results suggest that TRPM8 may contribute to tumor proliferation by controlling the PI3K-AKT-mTOR signaling pathway in PAAD. CONCLUSION: After careful evaluation of the accumulated data, we concluded that TRPM8 has potential as a prognostic indicator and prospective therapeutic target in PAAD.

Optical information hiding for different surface images.

Optical hiding often requires the selection of specific artificial optical components as carriers, which results in poor versatility of the carriers and high costs for the hiding system. To conceal secret information on different surfaces such as metal, wood, and paper, we propose an optical information hiding method. In this method, we use images of surfaces, whose grayscale histograms have the characteristic of symmetric distribution. Based on this characteristic, we first scramble the surface image, and then adjust part of the gray value of the surface image to the complementary value to embed the secret information into a scrambled surface image to generate a key image. In the extraction process, a projector is used to reproduce the scrambled surface image and the key image, which are then incoherently superimposed to extract the secret information using the human visual system. The extraction process does not require complex optical knowledge and is simple and feasible. Simulation experiments and optical experiments indicate that this method is applicable in practice and possesses good security and imperceptibility. Furthermore, we prove the reliability of this method by embedding secret information in different surface images, demonstrating the potential application of more surface images in the field of optical information hiding. Finally, we discuss the applicability of surface information images and analyze the imperceptibility of key images.

Lateral hypothalamus orexinergic projection to the medial prefrontal cortex modulates chronic stress-induced anhedonia but not anxiety and despair.

Chronic stress-induced anxiodepression is a common health problem, however its potential neurocircuitry mechanism remains unclear. We used behavioral, patch-clamp electrophysiology, chemogenetic, and optogenetic approaches to clarify the response of the lateral hypothalamus (LH) and the medial prefrontal cortex (mPFC) to stress, confirmed the structural connections between the LH and mPFC, and investigated the role of the LH-mPFC pathway in chronic stress-induced anxiodepression symptoms. Unpredictable chronic mild stress (UCMS) caused anxiodepression-like behaviors, including anxiety, anhedonia, and despair behaviors. We discovered that the activity of the LH and mPFC was both increased after restraint stress (RS), a stressor of UCMS. Then we found that the orexinergic neurons in the LH predominantly project to the glutamatergic neurons in the mPFC, and the excitability of these neurons were increased after UCMS. In addition, overactivated LH orexinergic terminals in the mPFC induced anhedonia but not anxiety and despair behaviors in naive mice. Moreover, chemogenetically inhibited LH-mPFC orexinergic projection neurons and blocked the orexin receptors in the mPFC alleviated anhedonia but not anxiety and despair behaviors in UCMS-treated mice. Our study identified a new neurocircuit from LH orexinergic neurons to mPFC and revealed its role in regulating anhedonia in response to stress. Overactivation of LHOrx-mPFC pathway selectively mediated chronic stress-induced anhedonia. In normal mice, the LHOrx-mPFC pathway exhibits relatively low activity. However, after chronic stress, the activity of orexinergic neuron in LH is overactivated, leading to an increased release of orexin into the mPFC. This heightened orexin concentration results in increased excitability of the mPFC through OX1R and OX2R, consequently triggering anhedonia.

Role of TRP Channels in Metabolism-Related Diseases.

Metabolic syndrome (MetS), with its high prevalence and significant impact on cardiovascular disease, poses a substantial threat to human health. The early identification of pathological abnormalities related to MetS and prevention of the risk of associated diseases is of paramount importance. Transient Receptor Potential (TRP) channels, a type of nonselective cation channel, are expressed in a variety of tissues and have been implicated in the onset and progression of numerous metabolism-related diseases. This study aims to review and discuss the expression and function of TRP channels in metabolism-related tissues and blood vessels, and to elucidate the interactions and mechanisms between TRP channels and metabolism-related diseases. A comprehensive literature search was conducted using keywords such as TRP channels, metabolic syndrome, pancreas, liver, oxidative stress, diabetes, hypertension, and atherosclerosis across various academic databases including PubMed, Google Scholar, Elsevier, Web of Science, and CNKI. Our review of the current research suggests that TRP channels may be involved in the development of metabolism-related diseases by regulating insulin secretion and release, lipid metabolism, vascular functional activity, oxidative stress, and inflammatory response. TRP channels, as nonselective cation channels, play pivotal roles in sensing various intra- and extracellular stimuli and regulating ion homeostasis by osmosis. They present potential new targets for the diagnosis or treatment of metabolism-related diseases.

The morphology and spectral characteristics of the compound eye of Agasicleshygrophila (Selman & Vogt, 1971) (Coleoptera, Chrysomelidae, Galerucinae, Alticini).

The first exploratory study was conducted on the compound eye morphology and spectral characteristics of Agasicleshygrophila (Selman & Vogt, 1971) to clarify its eye structure and its spectral sensitivity. Scanning electron microscopy, paraffin sectioning, and transmission electron microscopy revealed that A.hygrophila has apposition compound eyes with both eucones and open rhabdom. The micro-computed tomography (CT) results after 3D reconstruction demonstrated the precise position of the compound eyes in the insect's head and suggested that the visual range was mainly concentrated in the front and on both sides of the head. The electroretinogram (ERG) experiment showed that red, yellow, green, blue, and ultraviolet light could stimulate the compound eyes of A.hygrophila to produce electrical signals. The behavioural experiment results showed that both males and females had the strongest phototaxis to yellow light and positive phototaxis to red, green, and blue light but negative phototaxis to UV light. This study of the compound eyes of A.hygrophila will be helpful for decoding its visual mechanism in future studies.

Neural circuit mechanisms linking courtship and reward in Drosophila males.

Courtship has evolved to achieve reproductive success in animal species. However, whether courtship itself has a positive value remains unclear. In the present work, we report that courtship is innately rewarding and can induce the expression of appetitive short-term memory (STM) and long-term memory (LTM) in Drosophila melanogaster males. Activation of male-specific P1 neurons is sufficient to mimic courtship-induced preference and memory performance. Surprisingly, P1 neurons functionally connect to a large proportion of dopaminergic neurons (DANs) in the protocerebral anterior medial (PAM) cluster. The acquisition of STM and LTM depends on two distinct subsets of PAM DANs that convey the courtship-reward signal to the restricted regions of the mushroom body (MB) γ and α/ß lobes through two dopamine receptors, D1-like Dop1R1 and D2-like Dop2R. Furthermore, the retrieval of STM stored in the MB α'/ß' lobes and LTM stored in the MB α/ß lobe relies on two distinct MB output neurons. Finally, LTM consolidation requires two subsets of PAM DANs projecting to the MB α/ß lobe and corresponding MB output neurons. Taken together, our findings demonstrate that courtship is a potent rewarding stimulus and reveal the underlying neural circuit mechanisms linking courtship and reward in Drosophila males.

Risk factors of non-sentinel lymph node metastasis in breast cancer with 1-2 sentinel lymph node macrometastases underwent total mastectomy: a case-control study.

BACKGROUND: The randomized trials which include ACOSOG Z0011 and IBCSG 23-01 had found that the survival rates were not different in patients with cT1/2N0 and 1-2 sentinel lymph node (SLN)-positive, macro/micrometastases who underwent breast-conserving therapy, and micrometastases who underwent total mastectomy (TM), when axillary lymph node dissection (ALND) was omitted. However, for patients with cT1/2N0 and 1-2 SLN macrometastases who underwent TM; there was still insufficient evidence from clinical studies to support whether ALND can be exempted. This study aimed to investigate the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1-2 SLN macrometastases undergoing TM. METHODS: The clinicopathological data of 1491 breast cancer patients who underwent TM and SLNB from January 2017 to February 2022 were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for nSLN metastasis. RESULTS: A total of 273 patients with 1-2 SLN macrometastases who underwent TM were enrolled. Postoperative pathological data showed that 35.2% patients had nSLN metastasis. The results of multivariate analysis indicated that tumor size (TS) (P = 0.002; OR: 1.051; 95% CI: 1.019-1.084) and ratio of SLN macrometastases (P = 0.0001; OR: 12.597: 95% CI: 4.302-36.890) were the independent risk factors for nSLN metastasis in breast cancer patients with 1-2 SLN macrometastases that underwent TM. The ROC curve analysis suggested that when TS ≤22 mm and ratio of SLN macrometastases ≤0.33, the incidence of nSLN metastasis could be reduced to 17.1%. CONCLUSIONS: The breast cancer patients with cT1/2N0 stage, undergoing TM and 1-2 SLN macrometastases, when the TS ≤22 mm and macrometastatic SLN does not exceed 1/3 of the total number of detected SLN, the incidence of nSLN metastasis is significantly reduced, but whether ALND can be exempted needs further exploration.

A Neural Circuit Controlling Virgin Female Aggression Induced by Mating-related Cues in Drosophila.

Females increase aggression for mating opportunities and for acquiring reproductive resources. Although the close relationship between female aggression and mating status is widely appreciated, whether and how female aggression is regulated by mating-related cues remains poorly understood. Here we report an interesting observation that Drosophila virgin females initiate high-frequency attacks toward mated females. We identify 11-cis-vaccenyl acetate (cVA), a male-derived pheromone transferred to females during mating, which promotes virgin female aggression. We subsequently reveal a cVA-responsive neural circuit consisting of four orders of neurons, including Or67d, DA1, aSP-g, and pC1 neurons, that mediate cVA-induced virgin female aggression. We also determine that aSP-g neurons release acetylcholine (ACh) to excite pC1 neurons via the nicotinic ACh receptor nAChRα7. Together, beyond revealing cVA as a mating-related inducer of virgin female aggression, our results identify a neural circuit linking the chemosensory perception of mating-related cues to aggressive behavior in Drosophila females.

A neurotransmitter histamine mediating phototransduction and photopreference in Callosobruchus maculatus.

BACKGROUND: The biogenic amine histamine plays a critical role in the phototransduction and photopreference of most insects. Here, we study the function of histamine in Callosobruchus maculatus, a global storage pest. RESULTS: In our experiment, we initially identified the histidine decarboxylase (hdc) gene through bioinformation analysis. We subsequently investigated effects of hdc and histamine on the photopreference of C. maculatus using a combination of RNA interference (RNAi), electroretinograms (ERG), immunostaining, and photopreference behavior approaches. Our results showed that histamine was required for visual signal transduction of C. maculatus, and increased its photopreference regardless of the wavelength. CONCLUSION: This is the first study analyzing the molecular characteristics of C. maculatus photopreference, which forms the basis for a molecular mechanism for the effects of histamine on its visual transduction and preference. In practice, better understanding the photopreference patterns contributes to IPM (integrated pest management) for this storage pest. © 2023 Society of Chemical Industry.

Neurology care and the long-term outcomes of atrial fibrillation-related ischaemic stroke in China: median 3-year outcome from a high volume academic tertiary hospital.

OBJECTIVES: The initial medical contact of patients with atrial fibrillation (AF) and ischaemic stroke is often performed by neurologists. However, when stand care with oral anticoagulants (OACs) adherence and persistence was emphasised by cardiologists, data regarding the gap between current neurology care and standard care from Chinese tertiary hospitals is scarce and the long-term outcome is unknown. This study was to investigate the AF detection rate, the use of anticoagulation therapy and posthospital clinical outcomes associated with neurology care in patients with AF and ischaemic stroke in China. DESIGN: A retrospective cohort study. SETTING: Clinical data of all patients who had an ischaemic stroke discharged from the neurologic department of a high-volume academic hospital from 1 January 2013 to 31 December 2017 were analysed and patients were followed. PARTICIPANTS: Patients diagnosed with ischaemic stroke and AF were included. MAIN OUTCOME MEASURES: The usage of anticoagulation at discharge, the posthospital restroke rate and all-cause mortality. RESULTS: Among 5797 patients who had an ischaemic stroke, 373 (6.43%) patients were diagnosed with AF during hospitalisation. Among them, only 198 (53.66%) patients were on anticoagulation therapy at discharge. A total of 325 (88.08%) patients were accessible and received follow-up. After a median 3-year follow-up, 103 (31.69%) patients died due to all causes. Among them, 53 (16.31%) patients died from recurrent stroke. And 86 (26.46%) patients restroked. In multivariable analysis, patients without anticoagulation therapy, muscle strength

Function of TRPC1 in modulating hepatocellular carcinoma progression.

The liver is the main organ of metabolism in the human body, and it is easy to suffer from hepatitis, cirrhosis, liver cancer, and other diseases, the most serious of which is liver cancer. Worldwide, liver cancer is the most common and deadly malignant tumor, the third leading cause of cancer death in the world. Based on TCGA and ICGC databases, our research discovered the important role of TRPC1 in liver cancer through bioinformatics. The results showed that TRPC1 was over-expressed in hepatocellular carcinoma, and the higher the expression level of TRPC1, the worse the OS and the lower the survival rate. TRPC1 was a risk factor affecting the overall survival probability of hepatocellular carcinoma patients. By analyzing the function of the TRP family in liver cancer, TRPC1 might promote the occurrence of liver cancer by up-regulating common signal pathways in tumors such as tumor proliferation signature, and down-regulating important metabolic reactions such as retinol metabolism. In addition, TRPC1 could promote the development of liver cancer by up-regulating the expression of ABI2, MAPRE1, YEATS2, MTA3, TMEM237, MTMR2, CCDC6, AC069544.2, and NCBP2 genes. These results illustrate that TRPC1 is very valuable in the study of liver cancer.

Effects of lithium on aggression in Drosophila.

Lithium is a common medication used to treat mania and bipolar disorder, but the mechanisms by which lithium stabilizes mood and modifies aggression are still not fully understood. Here we found that acute but not chronic lithium significantly suppresses aggression without affecting locomotion in Drosophila melanogaster. Male flies treated with acute lithium are also less competitive than control males in establishing dominance. We also provided evidence that glycogen synthase kinase-3 (GSK-3), a well-known target of lithium, plays an important role in the anti-aggressive effect of lithium in Drosophila. Our genetic data showed that acute knockdown of GSK-3 in neurons can mimic the inhibitory effect of acute lithium on aggression, while specific overexpression of GSK-3 in a subset of P1 neurons profoundly promotes aggression which can be partially rescued by acute lithium application. Thus, these findings revealed the inhibitory effect of lithium on aggression in Drosophila and laid a groundwork for using Drosophila as a powerful model to investigate the mechanisms by which lithium reduces aggression.

Serotonin Signaling Modulates Sexual Receptivity of Virgin Female Drosophila.

The choice of females to accept or reject male courtship is a critical decision for animal reproduction. Serotonin (5-hydroxytryptamine; 5-HT) has been found to regulate sexual behavior in many species, but it is unclear how 5-HT and its receptors function to regulate different aspects of sexual behavior. Here we used Drosophila melanogaster as the model animal to investigate how 5-HT and its receptors modulate female sexual receptivity. We found that knockout of tryptophan hydroxylase (Trh), which is involved in the biosynthesis of 5-HT, severely reduced virgin female receptivity without affecting post-mating behaviors. We identified a subset of sexually dimorphic Trh neurons that co-expressed fruitless (fru), in which the activity was correlated with sexual receptivity in females. We also found that 5-HT1A and 5-HT7 receptors regulate virgin female receptivity. Our findings demonstrate how 5-HT functions in sexually dimorphic neurons to promote virgin female receptivity through two of its receptors.

Impaired learning and memory generated by hyperthyroidism is rescued by restoration of AMPA and NMDA receptors function.

Hyperthyroidism has been identified as a risk factor for cognitive disorders. The hippocampus is a key brain region associated with cognitive function, among which excitatory synapse transmission plays an important role in the process of learning and memory. However, the mechanism by which hyperthyroidism leads to cognitive dysfunction through a synaptic mechanism remains unknown. We investigated the synaptic mechanisms in the effects of hyperthyroidism in an animal model that involved repeated injection of triiodothyronine (T3). These mice displayed impaired learning and memory in the Novel object recognition test, Y-maze test, and Morris Water Maze test, as well as elevated anxiety in the elevated plus maze. Mature dendritic spines in the hippocampal CA1 region of hyperthyroid mice were significantly decreased, accompanied by decreased level of AMPA- and NMDA-type glutamate receptors in the hippocampus. In primary cultured hippocampal neurons, levels of AMPA- and NMDA-type glutamate receptors also decreased and whole-cell patch-clamp recording revealed that excitatory synaptic function was obviously attenuated after T3 treatment. Notably, pharmacological activation of AMPAR or NMDAR by intraperitoneal injection of CX546, an AMPAR agonist, or NMDA, an NMDAR agonist can restore excitatory synaptic function and corrected impaired learning and memory deficit in hyperthyroid mice. Together, our findings uncovered a previously unrecognized AMPAR and NMDAR-dependent mechanism involved in regulating hippocampal excitatory synaptic transmission and learning and memory disorders in hyperthyroidism.

Structural Investigation of the Interaction Mechanism between Chlorogenic Acid and AMPA Receptor via In Silico Approaches.

Chlorogenic acid (CGA), an important metabolite in natural plant medicines such as honeysuckle and eucommia, has been shown to have potent antinociceptive effects. Nevertheless, the mechanism by which CGA relieves chronic pain remains unclear. α-amino-3-hydroxy-5-methyl-4-isooxazolpropionic acid receptor (AMPAR) is a major ionotropic glutamate receptor that mediates rapid excitatory synaptic transmission and its glutamate ionotropic receptor AMPA type subunit 1 (GluA1) plays a key role in nociceptive transmission. In this study, we used Western blot, surface plasmon resonance (SPR) assay, and the molecular simulation technologies to investigate the mechanism of interaction between CGA and AMPAR to relieve chronic pain. Our results indicate that the protein expression level of GluA1 showed a dependent decrease as the concentration of CGA increased (0, 50, 100, and 200 µM). The SPR assay demonstrates that CGA can directly bind to GluA1 (KD = 496 µM). Furthermore, CGA forms a stable binding interaction with GluA1, which is validated by molecular dynamics (MD) simulation. The binding free energy between CGA and GluA1 is -39.803 ± 14.772 kJ/mol, where van der Waals interaction and electrostatic interaction are the major contributors to the GluA1-CGA binding, and the key residues are identified (Val-32, Glu-33, Ala-36, Glu-37, Leu-48), which play a crucial role in the binding interaction. This study first reveals the structural basis of the stable interaction between CGA and GluA1 to form a binding complex for the relief of chronic pain. The research provides the structural basis to understand the treatment of chronic pain and is valuable to the design of novel drug molecules in the future.

Drosulfakinin signaling modulates female sexual receptivity in Drosophila.

Female sexual behavior as an innate behavior is of prominent biological importance for survival and reproduction. However, molecular and circuit mechanisms underlying female sexual behavior is not well understood. Here, we identify the Cholecystokinin-like peptide Drosulfakinin (DSK) to promote female sexual behavior in Drosophila. Loss of DSK function reduces female receptivity while overexpressing DSK enhances female receptivity. We identify two pairs of Dsk-expressing neurons in the central brain to promote female receptivity. We find that the DSK peptide acts through one of its receptors, CCKLR-17D3, to modulate female receptivity. Manipulation of CCKLR-17D3 and its expressing neurons alters female receptivity. We further reveal that the two pairs of Dsk-expressing neurons receive input signal from pC1 neurons that integrate sex-related cues and mating status. These results demonstrate how a neuropeptide pathway interacts with a central neural node in the female sex circuitry to modulate sexual receptivity.

Layered MXene/Aramid Composite Film for a Soft and Sensitive Pressure Sensor.

In recent years, the two-dimensional material MXene has shown great advantages in the field of wearable electronics and pressure sensors. Toward advanced applications, achieving a conformal pressure sensor with ultrathin thickness and great flexibility through a simple preparation principle, while maintaining its high sensitivity and wide detection range, is still a key challenge for the development of high-performance pressure sensors. Herein, we proposed an optimized mild LiF/HCl etching scheme and successfully achieved a high-concentration (>25 mg/mL) preparation of few-layer Ti3C2Tx MXene. Combining the prepared MXene with an aramid nanofiber (ANF), we designed an ultrathin layered pressure sensor based on an MXene/ANF composite through layer-by-layer suction filtration. The mechanical strength is greatly enhanced by composition with the ANF, while the pure MXene film is fragile. The sensor achieves a high sensitivity of 16.7 kPa-1, wide detection range (>100 kPa), only 10 µm thickness, great flexibility, and up to 10% stretchability, which are greatly beneficial to practical sensors. We demonstrated the wide application perspective of the sensor in human motion monitoring and human-machine interfaces from low pressure (human pulse) to high pressure (push-up).

Bachmann bundle impairment following linear ablation of left anterior wall: impact on left atrial function.

We aimed to evaluate the effect of Bachmann bundle (BB) impairment on electrical and mechanical function of the left atrium (LA), as well as the long-term clinical impact of such impairment. We measured activation time in the five LA walls in 56 patients with atrial fibrillation. LA reservoir, conduit, and contractile function were also evaluated. Patients were divided into two groups based on ablation strategy: the circumferential pulmonary vein isolation (CPVI) group and CPVI with LA anterior wall linear ablation (LAAW) group. Patients in the CPVI + LAAW group were divided into two sub-groups based on ECG differences following ablation: the BB impairment group and intact BB group. LA activation time and function were then compared between the ablation strategy groups and the CPVI + LAAW subgroups. Patients in the CPVI + LAAW group exhibited longer activation times in the anterior and lateral walls of the LA, poorer LA synchrony, and reduced LA contractile and reservoir function when compared with those in the CPVI group. In the BB impairment subgroup, we observed a discrepancy between electrical/mechanical remodeling. Among five walls, activation time was longest in this region. BB impairment was also associated with reduced LA function. Significant changes in LA function and conductibility were observed in patients with anterior wall ablation, especially those with iatrogenic BB impairment.

A novel model of home-based, patient-tailored and mobile application-guided cardiac telerehabilitation in patients with atrial fibrillation: A randomised controlled trial.

OBJECTIVE: To assess the effectiveness of tele-monitored cardiac rehabilitation in patients who have undergone ablation for atrial fibrillation. DESIGN: Single-centre, prospective, assessment-blinded, randomised controlled trial. SETTING: Domiciliary rehabilitation with support from a tertiary care hospital. SUBJECTS: One hundred patients who underwent ablation for atrial fibrillation were recruited. INTERVENTIONS: Participants were randomly allocated to a 12-week standard rehabilitation treatment (control group) or a comprehensive, domiciliary, mobile application-guided and tele-monitored cardiac rehabilitation program (intervention group) in a 1:1 fashion. MAIN OUTCOME MEASURES: The primary endpoint was the improvement in VO2peak. The secondary outcomes included adherence, physical activity, beliefs related to cardiovascular disease and exercise self-efficacy. RESULTS: Ninety-seven patients completed follow-up. The mean VO2peak increased significantly in both the intervention group (n = 49) (baseline vs 12 weeks: 19.1 ± 4.7 vs 27.3 ± 5.6 ml/(min kg), P < 0.01) and the control group (n = 48) (baseline vs 12 weeks: 18.7 ± 4.9 vs 22.9 ± 6.3 ml/(min kg), P < 0.01). The results of the between-group analysis of aerobic capacity were significantly in favour of the intervention group. During the 12-week program, patients in the intervention group exhibited better adherence than those in the control group. Moreover, self-reported physical activity improved more in the intervention group than in the control group, as did the beliefs related to cardiovascular disease and exercise self-efficacy (all P < 0.01). CONCLUSIONS: Our domiciliary, mobile application-guided and tele-monitored cardiac rehabilitation program could lead to a more significant improvements in physical fitness, adherence and health beliefs than standard cardiac rehabilitation in patients who have undergone ablation for atrial fibrillation.