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Xiao-Dan Wu,1 Fan-Fang Zeng,1 Xiao-Xuan Yu,1 Pan-Pan Yang,1 Jun-Peng Wu,1 Ping Xv,2 Hai-Tang Wang,1 You-Ming Pei1 1Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510280, People’s Republic of ChinaCorrespondence: Hai-Tang Wang; You-Ming Pei, Department of Anesthesiology, Nanfang Hospital, Southern medical university, 1838 Guangzhou North Road, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel +86-18718911653 ; +86-15889942610, Fax +86 20-62787271 ; +86 20-62787271, Email wanghaitang8888@163.com; 71119099@qq.comPurpose: Chronic post-surgical pain (CPSP) is one of the adverse outcomes after surgery, especially in thoracotomy. However, the prevalence of CPSP in elderly adults (≥ 65 years), is still limited. Therefore, the present study was undertaken to establish and validate the prediction model of CPSP in those patients after thoracic surgery, including thoracotomy and video-assisted thoracoscopic surgery.Patients and Methods: This retrospective, observational single-center cohort study was conducted in Nanfang Hospital, Southern Medical University, which randomly and consecutively collected 577 elderly patients who underwent thoracic surgery between January 1, 2017, and December 31, 2020. According to the Akaike information criterion, the prediction model was built based on all the data and was validated by calibration with 500 bootstrap samples.Results: The mean age of participants was 69.09± 3.80 years old, and 63.1% were male. The prevalence of CPSP was 26.9%. Age more than 75 years, BMI, blood loss, longer length of hospital stays, and higher pre-operative neutrophil count were associated with CPSP. Except for these factors, we incorporated history of drinking to build up the prediction model. The areas under the curve (AUCs) of the prediction models were 0.66 (95% CI, 0.61– 0.71) and 0.64 (95% CI, 0.59– 0.69) in the observational and validation cohorts, respectively. And the calibration curve of the predictive model showed a good fit between the predicted risk of CPSP and observed outcomes in elderly patients.Conclusion: The present developed model may help clinicians to find high-risk elderly patients with CPSP after thoracic surgery and take corresponding measures in advance to reduce the incidence of CPSP and improve their life quality.Keywords: chronic post-surgical pain, the elderly, thoracic surgery, prediction model, nomogram

Han Cen,1– 3 Qin-Wen Wen,4 Han-Qing Zhang,4 Hang Yu,4 Zhen Zeng,2 Ting Jin,2 Ting-Hui Wang,4 Wen Qin,4 Hua Huang,4 Xiu-Di Wu4 1Institute of Geriatrics, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Department of Preventive Medicine, Medical School of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 4Department of Rheumatology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Xiu-Di Wu, Department of Rheumatology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, 59 Liuting Road, Ningbo, Zhejiang, 315010, People’s Republic of China, Tel +86 574 87085588, Fax +86 574 87291583, Email awu1100@aliyun.comPurpose: To investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients.Patients and Methods: A total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts – erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR > 0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including SLC19A1, ABCB1, ABCC1∼ 4 and ABCG2, were genotyped.Results: Multivariable analysis revealed that SLC19A1 rs12659 and rs3788200, ABCC2 rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and ABCC2 rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and ABCB1 rs1128503, rs4148737 and ABCC3 rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR > 0.6. With adjustment for corresponding confounders, SLC19A1 TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR > 0.6 compared with the most common haplotype CAGG. The ABCC2 haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR > 0.6 compared with the most common haplotype CCC.Conclusion: Our results highlight the potential of genetic polymorphisms within transporter genes, particularly SLC19A1 and ABCC2, as predictors of clinical response to MTX in Chinese RA patients.Keywords: rheumatoid arthritis, methotrexate, transporter, single-nucleotide polymorphism, clinical response

The objective of this study was to detect cerebral potentials elicited by proximal stimulation of the first sacral (S1) nerve root at the S1 dorsal foramen and to investigate latency and amplitude of the first cerebral potential. Tibial nerve SEP and S1 nerve root SEP were obtained from 20 healthy subjects and 5 patients with unilateral sciatic nerve or tibial nerve injury. Stimulation of the S1 nerve root was performed by a needle electrode via the S1 dorsal foramen. Cerebral potentials were recorded twice to document reproducibility. Latencies and amplitudes of the first cerebral potentials were recorded. Reproducible cerebral evoked potentials were recorded and P20s were identified in 36 of 40 limbs in the healthy subjects. The mean latency of P20 was 19.8 ± 1.6 ms. The mean amplitude of P20-N30 was 1.2 ± 0.9 μV. In the five patients, P40 of tibial nerve SEP was absent, while well-defined cerebral potentials of S1 nerve root SEP were recorded and P20 was identified from the involved side. This method may be useful in detecting S1 nerve root lesion and other disorders affecting the proximal portions of somatosensory pathway. Combined with tibial nerve SEP, it may provide useful information for diagnosis of lesions affecting the peripheral nerve versus the central portion of somatosensory pathway. [ABSTRACT FROM AUTHOR]

The aim of present study was to investigate the effect of baicalin on hypoxia/reoxygenation (H/R) injury in cardiomyocytes and the mechanisms involved, particularly in relation to cytokines. The cardiomyocytes for the H/R groups were placed into a hypoxic chamber for 12 h and then underwent reoxygenation for 1 h. The cells in the TNF-alpha groups were administered 100 ng/mL rrTNF-alpha and incubated for 13 h under normal conditions. The cells in the baicalin pretreatment groups were administered 10 muM baicalin 30 min prior to exposure to H/R or TNF-alpha. It was observed that pretreatment with baicalin (10 muM) significantly reduced the cell damage and death induced by H/R or TNF-alpha. In the culture medium of the H/R cells, the SOD activity increased, while TNF-alpha was decreased by baicalin. The levels of IL-6 in culture medium for H/R or TNF-alpha treated cells were suppressed by baicalin pretreatment. In contrast, the levels of IL-10 in culture medium for H/R or TNF-alpha treated cells were significantly elevated by baicalin. Moreover, baicalin inhibited the nuclear translocation of NF-kappaB induced by H/R or TNF-alpha. In conclusion, baicalin may protect cardiomyocytes from H/R injury through an anti-inflammatory mechanism. Copyright (c) 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: As a fascial plane block technique, further exploration is needed to determine the safety and efficacy of a peri-capsular nerve group (PENG) block in elderly patients with intertrochanteric femur fractures. We aimed to evaluate whether opioid consumption during a PENG block is better than a conventional opioid-based program for postoperative pain management after proximal femoral nail anti-rotation (PFNA)., Methods: We conducted a prospective, randomized, controlled trial comparing the efficacy of the PENG block with the control group for elderly patients undergoing primary PFNA under general anesthesia. The primary outcome was the cumulative administration of sufentanil during the first 48 h after surgery., Results: 110 participants (55 in each group) were included in the analysis. Cumulative Sufentanil consumption between the PENG group and the control group at 48 h was 132.6 ± 12.3 vs. 141.0 ± 15.3, with a difference of -8.4; 95% CI, -13.6 to -3.1, P = 0.002. Sufentanil consumption at 24 h was 78.3 ± 6.1 vs. 94.0 ± 10.2, with a difference of -15.7; 95% CI, -18.9 to -12.5, P < 0.001. There were statistical differences in the visual analogue scale score trajectories between the two groups at 48 h postoperatively (P < 0.001). The median time to first remedial analgesia was lower in the PENG block group than in the control group (P < 0.001). However, there was no difference in the time to first standing., Conclusion: Incorporating the PENG block into a multimodal analgesia regimen can decrease opioid consumption among elderly patients undergoing PFNA under general anesthesia., Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100054290, principal investigator: Xiao-dan, Wu, 13/12/2021)., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the institutional review board of Fujian Provincial Hospital (April 30, 2021; K2021-04–080) and was registered in the Chinese Clinical Trial Registry (ChiCTR2100054290) on December 13, 2021. This study followed the CONSORT guidelines and Declarations of Helsinki. Written informed consent was obtained from all participants in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Coupling carbon capture with electrocatalytic carbon dioxide reduction (CO 2 R) to yield high-value chemicals presents an appealing avenue for combating climate change, yet achieving highly selective electrocatalysts remains a significant challenge. Herein, two molecularly woven covalent organic frameworks (COFs) are designed, namely CuCOF and CuCOF + , with copper(I)-bisphenanthroline complexes as building blocks. The metal-organic helical structure unit made the CuCOF and CuCOF + present woven patterns, and their ordered pore structures and cationic properties enhanced their CO 2 adsorption and good conductivity, which is confirmed by gas adsorption and electrochemical analysis. In the electrocatalytic CO 2 R measurements, CuCOF + decorated with extra ethyl groups exhibit a main CO product with selectivity of 57.81%, outperforming the CuCOF with 42.92% CO at the same applied potential of 0.8 V RHE . After loading Pd nanoparticles, CuCOF-Pd and CuCOF + -Pd performed increased CO selectivity up to 84.97% and 95.45%, respectively. Combining the DFT theoretical calculations and experimental measurements, it is assumed that the molecularly woven cationic COF provides a catalytic microenvironment for CO 2 R and ensures efficient charge transfer from the electrode to the catalytic center, thereby achieving high electrocatalytic activity and selectivity. The present work significantly advances the practice of cationic COFs in real-time CO 2 capture and highly selective conversion to value-added chemicals., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

α-Fetoprotein (AFP)-producing gastric carcinoma (AFPGC) is a rare subtype of gastric cancer (GC) with controversial classification methods. Hepatoid adenocarcinoma of the stomach (HAS) is another rare subtype of GC. Its definition intersects with that of AFPGC, but it is much rarer. The present report describes the case of an elderly patient with GC and AFPGC and HAS features in a serum test and pathology, respectively, and proposes a new classification of GC subtypes based on histological and AFP-producing features. A 75-year-old woman presented with a history of polydipsia and polyuria for over a decade and dizziness for 1 day. Serum AFP levels gradually elevated from 183.70 to 397.70 ng/ml in 1 month after the patient's first clinic visit. Subsequent pathological findings from endoscopic biopsy samples confirmed a hepatoid focus with positive immunohistochemical staining for AFP. The patient underwent a laparoscopic-assisted radical total gastrectomy and esophagojejunal Roux-en-Y anastomosis, and the serum AFP levels decreased to the normal range after the surgery. The present case indicates the diagnostic value of both the serum AFP level and pathological examinations in the diagnosis of AFPGC and HAS, and also highlights the contemporary circumstances of the vague classification based on different criteria for these two subtypes. Furthermore, the present report proposes a new classification considering both histological and AFP-producing features (using both serum biomarkers and immunohistochemistry tests) to cover all cases encompassed by AFPGC and HAS under all definition methods. This new method would give more precise diagnoses and add value to the subsequent treatment decision-making., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Ye et al.)

Liquid porosimetry experiments reveal a peculiar trend of the intrusion pressure of water in hydrophobic Cu 2 (3,3',5,5'-tetraethyl-4,4'-bipyrazolate) MOF. At lower temperature (T) range, the intrusion pressure (P i ) increases with T. For higher T values, P i  first reaches a maximum and then decreases. This is at odds with the Young-Laplace law, which for systems showing a continuous decrease of contact angle with T predicts a corresponding reduction of the intrusion pressure. Though the Young-Laplace law is not expected to provide quantitative predictions at the subnanoscale of Cu 2 (tebpz) pores, the physical intuition suggests that to a reduction of their hydrophobicity corresponds a reduction of the P i . Molecular dynamics simulations and sychrothron experiments allowed to clarify the mechanism of the peculiar trend of P i with T. At increasing temperatures the vapor density within the MOF' pores grows significantly, bringing the corresponding partial pressure to ≈5 MPa. This pressure, which is consistent with the shift of P i observed in liquid porosimetry, represents a threshold to be overcame before intrusion takes place. Beyond some value of temperature, the phenomenon of reduction of hydrophobicity (and water surface tension) dominated over the opposite effect of increase of vapor pressure and P i inverts its trend with T., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Objective: To explore clinical effect of modified Chinese-way technique under shoulder arthroscopy in treating massive rotator cuff tears., Methods: From January 2019 to June 2022, 22 patients with massive rotator cuff tears who underwent arthroscopic rotator cuff repair with improved Chinese-way technique, including 10 males and 12 females, aged from 46 to 76 years old with an average of(64.14±7.45) years old;the courses of disease ranged from 5 to 14 months with an average of(8.32±2.42) months;19 patients were complete repaired, and 3 patients were partial repaired. Visual analogue scale (VAS) and University of California at Los Angeles (UCLA) scale were used to evaluate pain and function of shoulder joint preoperatively and 1 year postoperatively. Postoperative complications, the integrity of reconstructed tissue structure and the size of subacromial space were observed., Results: All patients were followed up from 12 to 34 months with an average of (17.14±5.93) months. Re-tear were occurred in 4 patients during MRI follow-up, but clinical symptoms of patients were improved significantly and they were satisfied with the treatment, the others were no complications such as incision infection, peripheral nerve injury, loosening and falling off of internal fixation anchors. Preoperative and 1 year after operation VAS were (8.05±1.12) and (1.82±1.50), UCLA scores were (7.45±1.65) and (31.41±2.87) respectively, and the difference was statistically significant ( P <0.05)., Conclusion: The modified Chinese-way technique under shoulder arthroscopy for the massive rotator cuff tear could relieve pain obviously and recovery postoperative function well, with satisfactory curative effect.

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Two new ent-labdane diterpenoids, hypoestesins A-B (1-2) and five new labdane diterpenoids, hypopurolides H-L (3-7), were isolated from the aerial parts of Hypoestes purpurea. All of the structures were fully determined based on extensive analysis of 1 H, 13 C, 2D NMR, and HRESIMS data. The absolute configurations of 1-3 was established through comparing the experimental and calculated ECD curves and the structure of 5 was confirmed by single crystal X-ray diffraction experiment. Compounds 5-7 were unusual C23 labdane diterpenoids having a γ-acetonyl-α, β-unsaturated γ-lactone unit and each assigned as C-15 epimeric mixture. Furthermore, cytotoxic and anti-inflammatory activities of 3-7 were evaluated. The results showed that 3 had remarkable cytotoxic activity against HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 cancer cell lines with IC 50 values ranging from 2.35 to 17.06 μM. Compound 4 showed moderate cytotoxic activity against HL-60 and SMMC-7721 cancer cell lines with IC 50 values of 15.12 ± 0.53 and 12.92 ± 0.60 μM, respectively. Furthermore, compound 4 was also found to exhibit inhibitory activity against NO production in RAW 264.7 macrophages with IC 50 values of 23.56 ± 0.99 μM, compared to the positive control L-NMMA with an IC 50 value of 41.11 ± 1.34 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Eight previously undescribed diterpenoids, caesamins A-H (1-8), were separated and identified from the seeds of Caesalpinia minax Hance. Their structures were characterized by extensive spectroscopic data and X-ray crystallographic analysis. Structurally, caesamin A (1) is the first cassane-type diterpenoid with a C23 carbon skeleton containing an unusual isopropyl. Caesamin F (6) represents the first example of cleistanthane diterpenoid from the genus Caesalpinia. Caesamins B (2) and F (6) exhibited inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages with IC 50 values of 45.67 ± 0.92 and 42.99 ± 0.24 μM, comparable to positive control 43.69 ± 2.62 μM of NG-Monomethyl-L-arginine. Furthermore, the chemotaxonomic significance of the isolates was discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Previous meta-analyses have investigated the efficacy of lipid-lowering therapies for atherosclerotic cardiovascular disease; however, few have focused on patients with acute coronary syndrome (ACS). This meta-analysis aimed to compare the benefits of intensive lipid-lowering therapy with those of background statin therapy in patients with ACS., Methods: Searches were performed on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for articles published until April 13, 2023. Randomized controlled trials that compared intensive lipid-lowering therapies and background statin therapies in patients with prior ACS and recorded the outcome of three-point major cardiovascular events (MACE) were included. The risk ratio (RR) with 95% confidence interval (CI) was used as a measure of primary and secondary outcomes., Results: Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83-0.94; p  < 0.001), recurrent ACS (RR, 0.82; 95% CI, 0.71-0.96; p  = 0.013), nonfatal myocardial infarction (MI) (RR, 0.87; 95% CI, 0.81-0.93; p  < 0.001), stroke (RR, 0.83; 95% CI, 0.73-0.94; p  = 0.003), and unstable angina-related hospitalization (RR, 0.57; 95% CI, 0.33-0.99; p  = 0.046), but not all-cause mortality (RR, 0.94; 95% CI, 0.82-1.07; p  = 0.329), cardiovascular disease-related mortality (RR, 0.96; 95% CI, 0.88-1.06; p  = 0.457) or coronary revascularization (RR, 0.89; 95% CI, 0.79-1.00; p  = 0.057)., Conclusions: Intensive lipid-lowering therapies may reduce the risk of three-point MACE, recurrent ACS, nonfatal MI, stroke, and hospitalization for unstable angina in patients with ACS undergoing background statin therapy. These results may assist in clinical decision-making for the secondary prevention of cardiovascular events to initiate intensive lipid-lowering therapies immediately after ACS.

Purpose: Sleep disorders are common globally. Probiotics may improve human microbial diversity, offering potential benefits for sleep disturbances by enhancing sleep quality and reducing disorders. We aimed to use a population-based study to investigate the association between yogurt (a probiotic food) and probiotic consumption with sleep disturbances in US adults., Methods: A total of 49,693 adults from the 2009-2018 National Health and Nutrition Examination Survey (NHANES) were included in the analyses. Sleep disorders and sleep duration were assessed according to the Sleep Disorders Questionnaire. The Dietary Questionnaire evaluated yogurt and dietary supplements containing probiotic consumption. After adjusting for confounding factors, weighted multivariable logistic regression and subgroup analyses were used to assess the association between yogurt and probiotic consumption and sleep status., Results: Of the study cohort, 3535 (14.24 %) participants consumed yogurt and/or dietary supplements containing probiotics. The prevalence of sleep disorders was 16.22 %. Only 53.51 % of the participants achieved the recommended amount of sleep (7-9 h), with 6.10 % and 33.48 % having excessive and insufficient sleep duration, respectively. Weighted Logistic regression models indicated a significant association of probiotic intake with a decreased risk of sleep disturbances compared with those without yogurt or probiotic consumption after adjustments. (For sleep disorders: OR: 0.96, 95 % CI 0.94-0.98, P < 0.001 ; for sleep duration: OR: 0.98, 95 % CI 0.96-1.00, P  = 0.081) Moreover, the effect size of the probiotic intake on sleep was especially significant in sex, race, and BMI subgroups., Conclusion: The present study first indicated that yogurt and probiotic consumption were associated with a reduced risk of sleep disturbances in US adults, particularly among males, whites, and those with a normal BMI. Incorporating yogurt or probiotics into the diet could serve as a public health strategy for improving sleep disturbances, though further investigation into the underlying mechanisms is needed., Competing Interests: The authors have no conflict of interest., (© 2024 The Authors.)

Objective: Adverse events associated with dexmedetomidine were analyzed using data from the FDA's FAERS database, spanning from 2004 to the third quarter of 2023. This analysis serves as a foundation for monitoring dexmedetomidine's safety in clinical applications., Methods: Data on adverse events associated with dexmedetomidine were standardized and analyzed to identify clinical adverse events closely linked to its use. This analysis employed various signal quantification analysis algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS)., Results: In the FAERS database, dexmedetomidine was identified as the primary suspect in 1,910 adverse events. Our analysis encompassed 26 organ system levels, from which we selected 346 relevant Preferred Terms (PTs) for further examination. Notably, adverse drug reactions such as diabetes insipidus, abnormal transcranial electrical motor evoked potential monitoring, acute motor axonal neuropathy, and trigeminal cardiac reflex were identified. These reactions are not explicitly mentioned in the drug's specification, indicating the emergence of new signals for adverse drug reactions., Conclusion: Data mining in the FAERS database has elucidated the characteristics of dexmedetomidine-related adverse drug reactions. This analysis enhances our understanding of dexmedetomidine's drug safety, aids in the clinical management of pharmacovigilance studies, and offers valuable insights for refining drug-use protocols., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zheng and Wu.)

Objective: Both depression and insomnia are found to be more prevalent in cancer patients compared to the general population. This study compared the network structures of depression and insomnia among cancer patients versus cancer-free participants (controls hereafter)., Method: The 8-item Center for Epidemiological Studies Depression Scale (CESD-8) and the 4-item Jenkins Sleep Scale (JSS-4) were used to measure depressive and insomnia symptoms, respectively. Propensity score matching (PSM) was used to construct the control group using data from the Health and Retirement Study (HRS). In total, a sample consisting of 2216 cancer patients and 2216 controls was constructed. Central (influential) and bridge symptoms were estimated using the expected influence (EI) and bridge expected influence (bridge EI), respectively. Network stability was assessed using the case-dropping bootstrap method., Result: The prevalence of depression (CESD-8 total score ≥ 4) in cancer patients was significantly higher compared to the control group (28.56 % vs. 24.73 %; P = 0.004). Cancer patients also had more severe depressive symptoms relative to controls, but there was no significant group difference for insomnia symptoms. The network structures of depressive and insomnia symptoms were comparable between cancer patients and controls. "Felt sadness" (EI: 6.866 in cancer patients; EI: 5.861 in controls), "Felt unhappy" (EI: 6.371 in cancer patients; EI: 5.720 in controls) and "Felt depressed" (EI: 6.003 in cancer patients; EI: 5.880 in controls) emerged as the key central symptoms, and "Felt tired in morning" (bridge EI: 1.870 in cancer patients; EI: 1.266 in controls) and "Everything was an effort" (bridge EI: 1.046 in cancer patients; EI: 0.921 in controls) were the key bridge symptoms across both groups., Conclusion: Although cancer patients had more frequent and severe depressive symptoms compared to controls, no significant difference was observed in the network structure or strength of the depressive and insomnia symptoms. Consequently, psychosocial interventions for treating depression and insomnia in the general population could be equally applicable for cancer patients who experience depression and insomnia., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. Financial disclosure The HRS is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan. The study was supported by the National Science and Technology Major Project for investigational new drug (2018ZX09201-014), the Beijing Hospitals Authority Clinical Medicine Development of special funding support (XMLX202128), and the University of Macau (MYRG2019-00066-FHS; MYRG2022-00187-FHS)., (Copyright © 2024. Published by Elsevier B.V.)

Inositol hexaphosphate (InsP 6 ) is the major storage form of phosphorus in seeds. Reducing seed InsP 6 content is a breeding objective in agriculture, as InsP 6 negatively impacts animal nutrition and the environment. Nevertheless, how InsP 6 accumulation is regulated remains largely unknown. Here, we identify a clade of receptor-like cytoplasmic kinases (RLCKs), named Inositol Polyphosphate-related Cytoplasmic Kinases 1-6 (IPCK1-IPCK6), deeply involved in InsP 6 accumulation. The InsP 6 concentration is dramatically reduced in seeds of ipck quadruple (T-4m/C-4m) and quintuple (C-5m) mutants, accompanied with the obviously increase of phosphate (Pi) concentration. The plasma membrane-localized IPCKs recruit IPK1 involved in InsP 6 synthesis, and facilitate its binding and activity via phosphorylation of GRF 14-3-3 proteins. IPCKs also recruit IPK2s and PI-PLCs required for InsP 4 /InsP 5 and InsP 3 biosynthesis respectively, to form a potential IPCK-GRF-PLC-IPK2-IPK1 complex. Our findings therefore uncover a regulatory mechanism of InsP 6 accumulation governed by IPCKs, shedding light on the mechanisms of InsP biosynthesis in eukaryotes., (© 2024. The Author(s).)

Three undescribed cassane diterpenoids, caesalpanins D-F (1-3), and seven known ones were isolated from the seeds of Caesalpinia sappan. Structures and absolute configurations of 1-3 were elucidated based on the extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. Structurally, compound 1 was the first example of 18-norcassane diterpenoid and 2 was a rare 20-norcassane diterpenoid having an unusual five-membered oxygen bridge between C-10/C-18. The anti-proliferative activity of 1, 3, and 4-10 against PANC-1 cells (pancreatic ductal adenocarcinoma cell line) was evaluated, and phanginin H (4) was found to exhibit anti-cancer activity with IC 50 value of 18.13 ± 0.63 μM. Compound 4 inhibited PANC-1 cell growth by arresting the cell cycle at G2/M phase via regulation of cyclin-dependent kinases, and the self-renewal and metastasis of PANC-1 cells by suppressing cancer cell stemness. Furthermore, compound 4 induced ROS generation and subsequently activated autophagy, which was demonstrated by the formation of autophagic vacuoles and dynamic change of autophagic flux. The induced ROS accumulation resulted in AMPK activation and subsequently regulation of mTORC1 activity and ULK phosphorylation, indicating that 4 triggered autophagy through ROS/AMPK/mTORC1 pathway. These findings suggested that 4 might potentially be an autophagy inducer for the therapy of pancreatic cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)