Clemastine-induced enhancement of hippocampal myelination alleviates memory impairment in mice with chronic pain.

Patients with chronic pain often experience memory impairment, but the underlying mechanisms remain elusive. The myelin sheath is crucial for rapid and accurate action potential conduction, playing a pivotal role in the development of cognitive abilities in the central nervous system. The study reveals that myelin degradation occurs in the hippocampus of chronic constriction injury (CCI) mice, which display both chronic pain and memory impairment. Using fiber photometry, we observed diminished task-related neuronal activity in the hippocampus of CCI mice. Interestingly, the repeated administration with clemastine, which promotes myelination, counteracts the CCI-induced myelin loss and reduced neuronal activity. Notably, clemastine specifically ameliorates the impaired memory without affecting chronic pain in CCI mice. Overall, our findings highlight the significant role of myelin abnormalities in CCI-induced memory impairment, suggesting a potential therapeutic approach for treating memory impairments associated with neuropathic pain.

Caenorhabditis elegans LIN-24, a homolog of bacterial pore-forming toxin, protects the host from microbial infection.

Aerolysin-like pore-forming protein (af-PFP) superfamily members are double-edge swords that assist the bacterial infection but shied bacteria from the host by various mechanisms in some species including the toad Bombina maxima and zebrafish. While members of this family are widely expressed in all kingdoms, especially non-bacteria species, it remains unclear whether their anti-bacterial function is conserved. LIN-24 is an af-PFP that is constitutively expressed throughout the Caenorhabditis elegans lifespan. Here, we observed that LIN-24 knockdown reduced the maximum lifespan of worms. RNA-seq analysis identified 323 differentially expressed genes (DEGs) post-LIN-24 knockdown that were enriched in "immune response" and "lysosome pathway," suggesting a possible role for LIN-24 in resisting microbial infection. In line with this, we found that Pseudomonas aeruginosa 14 (PA14) infection induced LIN-24 expression, and that survival after PA14 infection was significantly reduced by LIN-24 knockdown. In contrast, LIN-24 overexpression (LIN-24-OE) conferred protection against PA14 infection, with worms showing longer survival time and reduced bacterial load. Weighted gene co-expression network analysis of LIN-24-OE worms showed that the highest correlation module was enriched in factors related to immunity and the defense response. Finally, by predicting transcription factors from RNA-seq data and knocking down candidate transcription factors in LIN-24-OE worms, we revealed that LIN-24 may protect worms against bacterial infection by stimulating DAF-16-mediated immune responses. These findings agree with our previous studies showing an anti-microbial role for the amphibian-derived af-PFP complex ßγ-CAT, suggesting that af-PFPs may play a conserved role in combatting microbial infections. Further research is needed to determine the roles this protein family plays in other physio-pathological processes, such as metabolism, longevity, and aging.

Population pharmacokinetics and dosing regimen optimization of levetiracetam in epilepsy during pregnancy.

AIMS: The pharmacokinetics of levetiracetam (LEV) significantly changed during pregnancy. It is a great challenge to predict the adjusted doses of LEV to reach the preconception target concentrations. This study aimed to establish a population pharmacokinetic model of LEV in women with epilepsy (WWE) during pregnancy to analyse the factors of pharmacokinetic variability and to develop a model-based individualized dosing regimen. METHODS: A total of 166 concentration-time points from 37 WWE during pregnancy treated with LEV were collected to analyse LEV pharmacokinetics with nonlinear mixed-effects modelling. The dosing regimen was optimized by Monte Carlo simulations based on the final model. RESULTS: The LEV pharmacokinetics in pregnant WWE were best described by a 1-compartment model of first-order absorption and elimination. The population typical value of apparent clearance (CL/F) in the final model was estimated to be 3.82 L/h (95% confidence interval 3.283-4.357 L/h) with a relative standard error of 7.2%. Both total body weight (TBW) and trimester of pregnancy were significantly associated with LEV-CL/F during pregnancy; LEV-CL/F increased by 42.72% when TBW increased from 55 to 65 kg from the first trimester to the second trimester. Monte Carlo simulations showed that dosing regimens for LEV should be individualized based on the patient's TBW and trimester of pregnancy to maximize the likelihood of achieving the therapeutic range. CONCLUSION: This first population pharmacokinetic study of LEV in WWE during pregnancy supports the use of a weight-based and pregnancy-based dosing regimen and can lay a foundation for further optimizing the individualized dosing regimens.

Population pharmacokinetic analyses of tacrolimus in non-transplant patients: a systematic review.

BACKGROUND AND OBJECTIVES: Tacrolimus (TAC) has been increasingly used in patients with non-transplant settings. Because of its large between-subject variability, several population pharmacokinetic (PPK) studies have been performed to facilitate individualized therapy. This review summarized published PPK models of TAC in non-transplant patients, aiming to clarify factors affecting PKs of TAC and identify the knowledge gap that may require further research. METHODS: The PubMed, Embase databases, and Cochrane Library, as well as related references, were searched from the time of inception of the databases to February 2023, to identify TAC population pharmacokinetic studies modeled in non-transplant patients using a non-linear mixed-effects modeling approach. RESULTS: Sixteen studies, all from Asian countries (China and Korea), were included in this study. Of these studies, eleven and four were carried out in pediatric and adult patients, respectively. One-compartment models were the commonly used structural models for TAC. The apparent clearance (CL/F) of TAC ranged from 2.05 to 30.9 L·h-1 (median of 14.9 L·h-1). Coadministered medication, genetic factors, and weight were the most common covariates affecting TAC-CL/F, and variability in the apparent volume of distribution (V/F) was largely explained by weight. Coadministration with Wuzhi capsules reduced CL/F by about 19 to 43%. For patients with CYP3A5*1*1 and *1*3 genotypes, the CL/F was 39-149% higher CL/F than patients with CYP3A5*1*1. CONCLUSION: The optimal TAC dosage should be adjusted based on the patient's co-administration, body weight, and genetic information (especially CYP3A5 genotype). Further studies are needed to assess the generalizability of the published models to other ethnic groups. Moreover, external validation should be frequently performed to improve the clinical practicality of the models.

Dual-omics reveals temporal differences in acute sympathetic stress-induced cardiac inflammation following α1 and ß-adrenergic receptors activation.

Sympathetic stress is prevalent in cardiovascular diseases. Sympathetic overactivation under strong acute stresses triggers acute cardiovascular events including myocardial infarction (MI), sudden cardiac death, and stress cardiomyopathy. α1-ARs and ß-ARs, two dominant subtypes of adrenergic receptors in the heart, play a significant role in the physiological and pathologic regulation of these processes. However, little is known about the functional similarities and differences between α1- and ß-ARs activated temporal responses in stress-induced cardiac pathology. In this work, we systematically compared the cardiac temporal genome-wide profiles of acute α1-AR and ß-AR activation in the mice model by integrating transcriptome and proteome. We found that α1- and ß-AR activations induced sustained and transient inflammatory gene expression, respectively. Particularly, the overactivation of α1-AR but not ß-AR led to neutrophil infiltration at one day, which was closely associated with the up-regulation of chemokines, activation of NF-κB pathway, and sustained inflammatory response. Furthermore, there are more metabolic disorders under α1-AR overactivation compared with ß-AR overactivation. These findings provide a new therapeutic strategy that, besides using ß-blocker as soon as possible, blocking α1-AR within one day should also be considered in the treatment of acute stress-associated cardiovascular diseases.

Full-dimensional quantum mechanical study of three-body recombination for cold 4He-4He-20Ne system.

The increase of the number of the two-body recombination channels strongly challenges the numerical calculation of the accurate rates for the three-body recombination (TBR) process and its reverse process, collision-induced dissociation (CID), at ultracold temperatures. By taking the 4He-4He-20Ne collision system as an example, we have obtained the rates for its TBR and CID processes involving all four recombination channels, including the two-body states 4He2 (l = 0) and 4He20Ne (l = 0, 1, 2) with l the rotational quantum number. By using the adiabatic hyperspherical method, we have considered not only total angular momentum J = 0 but also J > 0 in the ultracold collision energies (E = 0.01 - 100 mK × kB). It is found that 4He2 (l = 0) is the major product after the TBR process in the ultracold limit (E ≤ 0.1 mK × kB). The TBR rate into 4He2 (l = 0) is nearly one order of magnitude larger than the sum of the other three products, 4He20Ne (l = 0, 1, 2). Moreover, the CID rates for the three 4He20Ne (l = 0, 1, 2) + 4He initial states are close to each other and are smaller than that for the 4He2 (l = 0) + 20Ne initial state. Additionally, we have, for the first time, performed the channel-resolved scattering calculation that can explain the above-mentioned findings quantitatively.

Melanin-like polydopamine nanoparticles mediating anti-inflammatory and rescuing synaptic loss for inflammatory depression therapy.

Inflammatory depression is closely related to neuroinflammation. However, current anti-inflammatory drugs have low permeability to cross blood-brain barrier with difficulties reaching the central nervous system to provide therapeutic effectiveness. To overcome this limitation, the nano-based drug delivery technology was used to synthesize melanin-like polydopamine nanoparticles (PDA NPs) (~ 250 nm) which can cross the blood-brain barrier. Importantly, PDA NPs with abundant phenolic hydroxyl groups function as excellent free radical scavengers to attenuate cell damage caused by reactive oxygen species or acute inflammation. In vitro experiments revealed that PDA NPs exhibited excellent antioxidative properties. Next, we aimed to investigate the therapeutic effect of PDA NPs on inflammatory depression through intraperitoneal injection to the lipopolysaccharide-induced inflammatory depression model in mice. PDA NPs significantly reversed the depression-like behavior. PDA NPs was also found to reduce the peripheral and central inflammation induced by LPS, showing that alleviated splenomegaly, reduced serum inflammatory cytokines, inhibited microglial activation and restored synaptic loss. Various experiments also showed that PDA NPs had good biocompatibility both in vivo and in vitro. Our work suggested that PDA NPs may be biocompatible nano-drugs in treating inflammatory depression but their clinical application requires further study.

3D simulation of percutaneous sustentaculum tali screw insertion in calcaneal fractures.

BACKGROUND: In calcaneal fractures, the percutaneous screw fixation (PSF) is currently considered to be the better choice, but it is difficult to accurately place the screw into the sustentaculum tali (ST) during the operation. In this study, the ideal entry point, angle, diameter and length of the screw were calculated by simulating the operation process. METHODS: We retrospectively collected the calcaneus computed tomography (CT) scans of 180 adults, DICOM-formatted CT-scan images of each patient were imported into Mimics software to establish calcaneus model. Virtual screws were placed on the lateral of the posterior talar articular surface (PTAS), the lateral edge of the anterior process of calcaneus (APC), and the calcaneal tuberosity, respectively, the trajectory and size of the screws were calculated. RESULTS: The mean maximum diameter of the PTAS screw was 42.20 ± 3.71 mm. The vertical distance between the midpoint of the APC optimal screw trajectory and the lowest point of the tarsal sinus was 10.67 ± 1.84 mm, and the distance between the midpoint of the APC optimal screw trajectory and the calcaneocuboid joint was 5 mm ~ 19.81 ± 2.08 mm. The mean maximum lengths of APC screws was 44.69 ± 4.81 mm, and the Angle between the screw and the coronal plane of the calcaneus from proximal to distal was 4.72°±2.15° to 20.52°±3.77°. The optimal point of the maximum diameter of the calcaneal tuberosity screw was located at the lateral border of the achilles tendon endpoint. The mean maximum diameters of calcaneal tuberosity screws was 4.46 ± 0.85 mm, the mean maximum lengths of screws was 65.31 ± 4.76 mm. We found gender-dependent differences for the mean maximum diameter and the maximum length of the three screws. CONCLUSIONS: The study provides effective positioning for percutaneous screw fixation of calcaneal fractures. For safer and more efficient screw placement, we suggest individualised preoperative 3D reconstruction simulations. Further biomechanical studies are needed to verify the function of the screw.

A WRKY transcription factor, TaWRKY42-B, facilitates initiation of leaf senescence by promoting jasmonic acid biosynthesis.

BACKGROUND: Leaf senescence comprises numerous cooperative events, integrates environmental signals with age-dependent developmental cues, and coordinates the multifaceted deterioration and source-to-sink allocation of nutrients. In crops, leaf senescence has long been regarded as an essential developmental stage for productivity and quality, whereas functional characterization of candidate genes involved in the regulation of leaf senescence has, thus far, been limited in wheat. RESULTS: In this study, we analyzed the expression profiles of 97 WRKY transcription factors (TFs) throughout the progression of leaf senescence in wheat and subsequently isolated a potential regulator of leaf senescence, TaWRKY42-B, for further functional investigation. By phenotypic and physiological analyses in TaWRKY42-B-overexpressing Arabidopsis plants and TaWRKY42-B-silenced wheat plants, we confirmed the positive role of TaWRKY42-B in the initiation of developmental and dark-induced leaf senescence. Furthermore, our results revealed that TaWRKY42-B promotes leaf senescence mainly by interacting with a JA biosynthesis gene, AtLOX3, and its ortholog, TaLOX3, which consequently contributes to the accumulation of JA content. In the present study, we also demonstrated that TaWRKY42-B was functionally conserved with AtWRKY53 in the initiation of age-dependent leaf senescence. CONCLUSION: Our results revealed a novel positive regulator of leaf senescence, TaWRKY42-B, which mediates JA-related leaf senescence via activation of JA biosynthesis and has the potential to be a target gene for molecular breeding in wheat.

[Complex network analysis of combination medication of patients with kidney malignant tumor based in real world].

Kidney malignant tumor is a type of primary renal cell carcinoma, and mainly refers to renal cancer. The incidence of kidney cancer and the number of hospital cases in China have been increasing. Based on the clinical medicine information of patients in the hospital information system(HIS) database of 37 hospitals in China, the combined medication of patients with kidney malignant tumor were analyzed by Tabu search algorithm, so as to analyze the combined medication of patients with kidney malignant tumor in real world. A total of 7 095 patients with kidney malignant tumor were included, the ratio of males to females was 2.11∶1, and the ratio of male patients increased gradually with age. About 3 933 patients(55.43%) showed a superior effect among those patients. The common therapies of patients with kidney malignant tumor were anti-tumor therapies and symptomatic therapies, including anti-infection, regulation of electrolyte balance, sedation and analgesia, analgesic, regulation of gastrointestinal function. The whole population of patients with kidney malignant tumor were mostly treated with anti-tumor drugs combined with more symptomatic therapies, while the anti-tumor therapies of the superiority population of patients were less combined with other drugs, with less combined medication. The result may be related to the stage of tumor or individual response to the therapeutic regimen. No matter for the whole population or for the superiority population of patients with kidney malignant tumor, the therapies was mainly Western medicines. Based on the pathogenesis of deficiency in origin and excess in superficiality with kidney malignant tumor, Chinese subgroups with formula for clearing heat and removing toxicity, formula for vigorate Qi and replenish the blood, formula for regulate Qi and invigorate the blood, laxative and hemostatic were more commonly used. In the future, further studies shall be conducted for combined therapies for patients of different stages, so as to play the advantages of multi-target, overall regulation, toxicity reduction and efficacy enhancement of traditional Chinese medicine, improve the life quality of patients with kidney malignant tumor, prolong their life time, and improve the survival rate of patients.

[Geological distribution of exudation and storage area of Tibetan medicine Zha-xun in Sichuan province based on GIS].

Zha-xun is widely used in Tibetan medicine and is also an international traditional medicine. This study believes that the black organic matter constituting Zha-xun is mainly stored in the rocks. The exudation points of Zha-xun mostly distribute on the cliffs of high mountains, which makes it difficult to evaluate its resource distribution and storage area. This paper was aimed at the exudation environment of Tibetan medicine Zha-xun in Sichuan province and 6 ecological environmental factors of the Zha-xun were determined via the field investigation. Combining with these 6 factors as well as the GIS data of Sichuan province, ArcGIS software was used to extract ideal environmental factors which are suitable for exudation of Zha-xun, including geology types, geomorphological types, altitude, slope, vegetation types, and mean annual temperature. The spatial overlay analyses on the extracted environmental factors were carried out to predict the distribution area of Zha-xun in Sichuan province. Afterwards, field investigation was conducted to verify the prediction. The prediction showed that the exudation spots of Zha-xun in Sichuan province mainly located in 29 counties including 12 in Aba Prefecture, 15 in Ganzi Prefecture, and Muli County and Dechang County in Liangshan Prefecture. The deposit areas of Zha-xun were located in the Triassic, Devonian and Silurian strata and were basically distributed in 9 basins, including Dingqu River, Yalong River, Xianshui River, Dadu River, Suomo River, Minjiang River and Baishui River, characterized by a fragmented patch-like distribution along the mountain ranges, and the exudation spots of Zha-xun were mainly scattered among the rain-free cliffs' concavities of river valleys at a certain altitude. The prediction was consistent with the field investigation results, which suggested that it is possible and feasible to predict distribution of Zha-xun resources based on GIS-analysis. The study may provide a scientific basis for comprehensive investigations into Zha-xun's distribution and formation mechanism, thus promoting rational development and utilization of Zha-xun resources.

[Research progress of Tibetan medicine "Zha-xun"].

Zha-xun is widely used in Tibetan medicine and is also an international traditional medicine. This article would summarize the use status and research progress of Zha-xun by various ethnic groups all over the world, and the results show that it has various synonyms but most of them imply its most characteristic feature-outflow from the rock; Zha-xun resources are distributed in various places of the world, and its bearing spots are closely related to the geological structure; there are sharp arguments on the origins of Zha-xun, mainly including the minerals origin, biological fossils origin, biological origin, etc. Zha-xun has multiple functions and is mainly used to treat stomach disease, liver disease and rheumatoid arthritis in China, and premature ejaculation, impotence, vaginitis embolism in foreign countries. "Iron" Zha-xun is used into medicines both at home and abroad. According to ancient materia medica texts, it was mainly classified into five types, including gold Zha-xun, silver Zha-xun, copper Zha-xun, iron Zha-xun and lead Zha-xun mainly based on the predominance of color rather than the minerals contained. It is commonly believed by the domestic and foreign scholars that humic acid is the main medicinal part of Zha-xun, and their studies have found that it has a variety of pharmacological activities such as anti-ulcer, anti-inflammatory, liver protection, analgesia, immune regulation, increasing sexual desire and fertility, antioxidation, antibacterial, antidiabetic, antiepileptic, antipsychotic, etc. This paper provides a scientific basis for the rational utilization of Zha-xun resources.

Neuroprotective Effect of Salvianolic Acids against Cerebral Ischemia/Reperfusion Injury.

This study investigated the neuroprotective effect of salvianolic acids (SA) against ischemia/reperfusion (I/R) injury, and explored whether the neuroprotection was dependent on mitochondrial connexin43 (mtCx43) via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. In vitro, we measured astrocyte apoptosis, mitochondrial membrane potential, and also evaluated the morphology of astrocyte mitochondria with transmission electron microscopy. In vivo, we determined the cerebral infarction volume and measured superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. Additionally, mtCx43, p-mtCx43, AKT, and p-AKT levels were determined. In vitro, we found that I/R injury induced apoptosis, decreased cell mitochondrial membrane potential (MMP), and damaged mitochondrial morphology in astrocytes. In vivo, we found that I/R injury resulted in a large cerebral infarction, decreased SOD activity, and increased MDA expression. Additionally, I/R injury reduced both the p-mtCx43/mtCx43 and p-AKT/AKT ratios. We reported that both in vivo and in vitro, SA ameliorated the detrimental outcomes of the I/R. Interestingly, co-administering an inhibitor of the PI3K/AKT pathway blunted the effects of SA. SA represents a potential treatment option for cerebral infarction by up-regulating mtCx43 through the PI3K/AKT pathway.

Mechanism of Mitochondrial Connexin43's Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury.

We observed mitochondrial connexin43 (mtCx43) expression under cerebral ischemia-reperfusion (I/R) injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO). Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. MtCx43, p-mtCx43, protein kinase C (PKC), and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX) and diazoxide (DZX) groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD) groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA) reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

[Classics textual research and using situation investigation of Tibetan medicine "Zha-xun"].

In this article the classics textual research to the origin of "Zha-xun" was carried out, the ethnobotanical research methods, the origin of visits, key informant interviews, sample collection and textual research were applied in the research. The results showed that the hypothesis of Zha-xun"s origin mainly included "source of mine", "source of feces", "source of monkey menstrual blood" in China. There were "source of fossil", "source of the plant secretion" abroad. The authors had interviewed the villagers at origin, herbalists, Tibetan doctors, herb dealers, foreign scholars for a total of 18 people, and collecting 45 batches medicinal materials. According to ancient Tibetan classics textual and Tibetan medicine doctors' views, medicinal materials were divided into the genuine and the substitutes. The genuine was identified as ancient so-called "iron" type "Zha-xun", and the substitute was fecal pellet bonding briquette. According to the field survey and literature research, "source of fossil" more in line with substance of Zha-xun was derived from the rock. As the results, the author believed that Zha-xun was the mixture of organic fossils from the rock seepage with flying squirrel, pika feces. So it is needed to be set up Zha-xun classification standard to evaluate the quality of medicinal materials. Meanwhile, it was necessary to further clarify fecal pellet substitute rationality. Above all, this article clarified the status of the use of Tibetan medicine-"Zha-xun", and laid the foundation of species systematics and quality standards research of "Zha-xun".

Mammalian target of rapamycin signaling inhibition ameliorates vascular calcification via Klotho upregulation.

Vascular calcification (VC) is a major risk factor for cardiovascular mortality in chronic renal failure (CRF) patients, but the pathogenesis remains partially unknown and effective therapeutic targets should be urgently explored. Here we pursued the therapeutic role of rapamycin in CRF-related VC. Mammalian target of rapamycin (mTOR) signal was activated in the aortic wall of CRF rats. As expected, oral rapamycin administration significantly reduced VC by inhibiting mTOR in rats with CRF. Further in vitro results showed that activation of mTOR by both pharmacological agent and genetic method promoted, while inhibition of mTOR reduced, inorganic phosphate-induced vascular smooth muscle cell (VSMC) calcification and chondrogenic/osteogenic gene expression, which were independent of autophagy and apoptosis. Interestingly, the expression of Klotho, an antiaging gene that suppresses VC, was reduced in calcified vasculature, whereas rapamycin reversed membrane and secreted Klotho decline through mTOR inhibition. When mTOR signaling was enhanced by either mTOR overexpression or deletion of tuberous sclerosis 1, Klotho mRNA was further decreased in phosphate-treated VSMCs, suggesting a vital association between mTOR signaling and Klotho expression. More importantly, rapamycin failed to reduce VC in the absence of Klotho by using either siRNA knockdown of Klotho or Klotho knockout mice. Thus, Klotho has a critical role in mediating the observed decrease in calcification by rapamycin in vitro and in vivo.

High Expression of PXMP4 in Hepatocellular Carcinoma Tissues.

OBJECTIVE: To analyze the high expression of peroxisome membrane protein 4 (PXMP4) in hepatocellular carcinoma (HCC) and its clinical significance. METHODS: The expression of PXMP4 mRNA in HCC tissues and corresponding adjacent tissues was detected by Q-PCR, and the expression of PXMP4 protein was detected by Western blot and immunohistochemistry. The correlation of PXMP4 protein expression with clinicopathological features and prognosis of HCC was analyzed. RESULTS: The expression levels of PXMP4 mRNA and protein in HCC tissues were significantly higher than those in adjacent tissues (P < 0.05), and its high expression was significantly correlated with tumor differentiation, lymph node metastasis, depth of invasion and TNM stage (P < 0.05). Patients with high expression of PXMP4 had a poor prognosis (P < 0.05). CONCLUSION: The high expression of PXMP4 may promote the occurrence and development of HCC, and inhibition of PXMP4 may be one of the potential molecular targets for targeted therapy of HCC.

The application progress of magnetic solid-phase extraction for heavy metal analysis in food: a mini review.

The emerging sample pretreatment technique of magnetic solid-phase extraction (MSPE) has drawn the attention of researchers owing to its advantages of less reagent consumption, fast separation/enrichment process, high adsorption capacity, and simple operation. This paper presents a review of synthesis techniques, classification, and analysis procedures for MSPE in the detection of heavy metals in food. Magnetic adsorbents derived from silica, metal oxides, carbon, polymers, etc., are applied for the detection of heavy metals in food. Then, the recent development of the technology of MSPE for the analysis of heavy metal extraction in food is summarized in detail. Finally, the future outlook for the improvement of MSPE is also discussed.

Verteporfin suppressed mitophagy via PINK1/parkin pathway in endometrial cancer.

Endometrial cancer (EC) is a malignancy that poses a threat to woman's health worldwide. Building upon prior work, we explored the inhibitory effect of verteporfin on EC. We showed that verteporfin can damage the mitochondria of EC cells, leading to a decrease of mitochondrial membrane potential and an increase in ROS (reactive oxygen species). In addition, verteporfin treatment was shown to inhibit the proliferation and migration of EC cells, promote apoptosis, and reduce the expression of mitophagy-related proteins PINK1/parkin and TOM20. The ROS inhibitor N-Acetyl Cysteine was able to rescue the expression of PINK1/parkin proteins. This suggests that verteporfin may inhibit mitophagy by elevating ROS levels, thereby inhibiting EC cell viability. The effect of verteporfin on mitophagy supports further investigation as a potential therapeutic option for EC.

SynCAM1 deficiency in the hippocampal parvalbumin interneurons contributes to sevoflurane-induced cognitive impairment in neonatal rats.

AIMS: Sevoflurane is widely used for general anesthesia in children. Previous studies reported that multiple neonatal exposures to sevoflurane can induce long-term cognitive impairment in adolescent rats, but the underlying mechanisms were not defined. METHODS: Postnatal day 6 (P6) to P8 rat pups were exposed to 30% oxygen with or without 3% sevoflurane balanced with air. The Y maze test (YMT) and Morris water maze (MWM) tests were performed in some cohorts from age P35 to assess cognitive functions, and their brain samples were harvested at age P14, 21, 28, 35, and 42 for measurements of various molecular entities and in vivo electrophysiology experiments at age P35. RESULTS: Sevoflurane exposure resulted in cognitive impairment that was associated with decreased synCAM1 expression in parvalbumin (PV) interneurons, a reduction of PV phenotype, disturbed gamma oscillations, and dendritic spine loss in the hippocampal CA3 region. Enriched environment (EE) increased synCAM1 expression in the PV interneurons and attenuated sevoflurane-induced cognitive impairment. The synCAM1 overexpression by the adeno-associated virus vector in the hippocampal CA3 region restored sevoflurane-induced cognitive impairment, PV phenotype loss, gamma oscillations decrease, and dendritic spine loss. CONCLUSION: Our data suggested that neonatal sevoflurane exposure results in cognitive impairment through decreased synCAM1 expression in PV interneurons in the hippocampus.