Pemigatinib, a selective FGFR inhibitor overcomes ABCB1-mediated multidrug resistance in cancer cells.

P: -glycoprotein (P-gp/ABCB1) overexpression is one of the primary causes of multidrug resistance (MDR). Therefore, it is crucial to discover effective pharmaceuticals to combat multidrug resistance mediated by ABCB1. Pemigatinib is a selective the fibroblast growth factor receptor (FGFR) inhibitor that is used to treat a variety of solid tumors, Clinical Trials for Urothelial Carcinoma (NCT02872714) completed its research on Pemigatinib. This study aimed to determine whether Pemigatinib can reverse ABCB1-mediated multidrug resistance, as well as its mechanism of action. Pemigatinib substantially reversed ABCB1-mediated multidrug resistance, as determined by a CCK8 assay, and immunofluorescence experiments revealed that Pemigatinib had no effect on the intracellular localization of ABCB1. Pemigatinib was discovered to increase intracellular drug accumulation, thereby reversing multidrug resistance. In addition, Docking analysis revealed that Pemigatinib and ABCB1 have a high affinity for one another. This study concludes that Pemigatinib is capable of reversing the multidrug resistance mediated by ABCB1, offering ideas and references for the clinical application of Pemigatinib.

Discovery of Unusual Ajmaline-Macroline Type Bisindole Alkaloids from Alstonia macrophylla by Building Blocks-Based Molecular Networking.

Three unusual ajmaline-macroline type bisindole alkaloids, alsmaphylines A-C, together with their postulated biogenetic precursors, were isolated from the stem barks and leaves of Alstonia macrophylla via the building blocks-based molecular network (BBMN) strategy. Alsmaphyline A represents a rare ajmaline-macroline type bisindole alkaloid with an S-shape polycyclic ring system. Alsmaphylines B and C are two novel ajmaline-macroline type bisindole alkaloids with N-1-C-21' linkages, and the former possesses an unconventional stacked conformation due to the presence of intramolecular noncovalent interactions. The chemical structures including absolute configurations of alsmaphylines A-C were established by comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray crystallography. In addition, a plausible biosynthetic pathway of these bisindole alkaloids as well as their ability to promote the protein synthesis on HT22 cells were discussed.

Confinement of 1D Chain and 2D Layered CuI Modules in K-INA-R Frameworks via Coordination Assembly: Structure Regulation and Semiconductivity Tuning.

Herein, we present a new series of CuI-based hybrid materials with tunable structures and semiconducting properties. The CuI inorganic modules can be tailored into a one-dimensional (1D) chain and two-dimensional (2D) layer and confined/stabilized in coordination frameworks of potassium isonicotinic acid (HINA) and its derivatives (HINA-R, R = OH, NO2, and COOH). The resulting CuI-based hybrid materials exhibit interesting semiconducting behaviors associated with the dimensionality of the inorganic module; for instance, the structures containing the 2D-CuI module demonstrate significantly enhanced photoconductivity with a maximum increase of five orders of magnitude compared to that of the structures containing the 1D-CuI module. They also represent the first CuI-bearing hybrid chemiresistive gas sensors for NO2 with boosted sensing performance and sensitivity at multiple orders of magnitude over that of the pristine CuI. Particularly, the sensing ability of CuI-K-INA containing both 1D- and 2D-CuI modules is comparable to those of the best NO2 chemiresistors reported thus far.

The Effect of Bilirubin on Clinical Outcomes of Patients With Colorectal Cancer Surgery: A Ten-Year Volume Single-Center Retrospective Study.

The current study aimed to evaluate the effect of bilirubin on the outcomes of colorectal cancer (CRC) in patients who underwent radical CRC surgery. The levels of serum bilirubin, including total bilirubin (TBil), direct bilirubin (DBil) and indirect bilirubin (IBil), were divided into higher groups and lower groups according to the median. Multivariate logistic regression was performed to analyze the independent predictors for overall complications and major complications. For TBil, the hospitalization time of the higher TBil group was longer than that of the lower TBil group (p = 0.014 < 0.05). For DBil, the higher DBil group had longer operation times (p < 0.01), more intraoperative bleeding (p < 0.01), longer hospital stays (p < 0.01), and higher rates of overall complications (p < 0.01) and major complications (p = 0.021 < 0.05) than the lower DBil group. For the IBil group, blood loss during operation (p < 0.01) and hospital stays (p = 0.041 < 0.05) in the higher IBil group were lower than those in the lower IBil group. In terms of complications, we found that DBil was an independent predictor for overall complications (p < 0.01, OR = 1.036, 95% CI = 1.014-1.058) and major complications (p = 0.043, HR= 1.355, 95% CI= 1.009-1.820). Higher preoperative DBil increase the risk of complications after primary CRC surgery.

The Use of Metformin and Postoperative Insulin Pump Were Predictive Factors for Outcomes of Diabetic Colorectal Cancer Patients after Surgery.

PURPOSE: This present study aims to explore the influence of metformin and postoperative insulin pump use on colorectal cancer (CRC) patients with type II diabetes mellitus (T2DM) who received surgery in terms of short-term and long-term outcomes. METHODS: 613 CRC patients who had comorbid T2DM and received surgery at a single clinical center from Jan, 2011 to Dec, 2021 were included in this study. Univariate and multivariate logistic regression analyses were used to find predictive factors for overall complications and major complications. Cox regression analyses was used to find prognostic factors for overall survival (OS) and disease-free survival (DFS). All statistical analysis was performed using SPSS (version 22.0) software. The Kaplan-Meier curve was used to show the OS and DFS between the insulin pump group and the no insulin pump group. RESULTS: Multivariate logistic regression analysis reported that lower body mass index (BMI) (p < 0.01, OR = 0.922, 95% CI = 0.870-0.977) and metformin use (p = 0.03, OR = 0.643, 95% CI = 0.431-0.959) were independent protective factors for overall complications, and insulin pump after surgery (p < 0.01, OR = 3.991, 95% CI = 2.434-6.544) was an independent risk factor for overall complications. As for major complications, metformin use (p = 0.042, OR = 0.274, 95% CI = 0.079-0.956) and insulin pump after surgery (p = 0.03, OR = 2.892, 95% CI = 1.107-7.552) remained independent protective factors and independent risk factors, respectively. Moreover, in Cox regression analyses, age (OS: p < 0.01, HR = 1.032, 95% CI = 1.008-1.057; DFS: p < 0.01, HR = 1.030, 95% CI = 1.008-1.052), tumor stage (OS: p < 0.01, HR = 1.709, 95% CI = 1.244-2.346; DFS: p < 0.01, HR = 1.696, 95% CI = 1.276-2.254), and Insulin pump after surgery (OS: p < 0.01, HR = 2.923, 95% CI = 1.887-4.527; DFS: p < 0.01, HR = 2.671, 95% CI = 1.779-4.009) were independent prognostic factors for both OS and DFS. After comparing the OS and DFS between the insulin pump group and the no insulin pump group, patients who received postoperative insulin pump had worse OS and DFS in all tumor node metastasis (TNM) stages (p < 0.01). CONCLUSION: Diabetic CRC patients who used metformin had a lower risk of postoperative complications. However, there was no difference from patients not using metformin in terms of survival. Furthermore, patients receiving postoperative insulin pump had more postoperative complications and worse survival in all TNM stages.

Impact of type 2 diabetes mellitus on short-term and long-term outcomes of stage iv colorectal cancer patients after primary surgery: a propensity score matching analysis.

PURPOSE: This study aims to investigate the influence of type 2 diabetes mellitus (T2DM) on stage IV colorectal cancer (CRC) patients performed primary surgery in terms of short-term and long-term outcomes. METHODS: Patients diagnosed with stage IV CRC and received primary CRC surgery at a single clinical center from Jan, 2013 to Jan, 2020 were included in this study. Baseline characteristics, short-term and long-term outcomes were compared between the T2DM group and the Non-T2DM group. Univariate and multivariate analysis were used to find risk factors for overall survival (OS). Propensity score matching (PSM) using a 1:1 ratio was used to minimize selective bias between the two groups. Statistical analysis was performed using SPSS (version 22.0) software. RESULTS: A total of 302 eligible patients were enrolled, and there were 54 (17.9%) patients with T2DM, and 248 (82.1%) patients without T2DM. The T2DM group had more older patients (P < 0.01), higher body mass index (BMI) (P < 0.01), and a higher proportion of hypertension (P < 0.01) than the Non-T2DM group. After PSM, there were 48 patients in each group. There were no significant differences in short-term outcomes or OS between the two groups, either before or after PSM (P > 0.05). In multivariate analysis, older age (P < 0.01, HR = 1.032, 95% CI = 1.014-1.051) and larger tumor size (P < 0.01, HR = 1.760, 95% CI = 1.179-2.626) were independent factors for OS. CONCLUSION: Although T2DM did not influence short-term outcomes or OS in stage IV CRC patients after primary surgery, age and tumor size might have predictive value for OS.

Do colorectal cancer patients with a postoperative stoma have sexual problems? A pooling up analysis of 2566 patients.

PURPOSE: This study aimed to evaluate the effect of the stoma on sexual function in colorectal cancer patients. METHODS: Search strategy was conducted in four databases including PubMed, Embase, the Cochrane Library, and Medline on Nov 20, 2022. After that, the quality of eligible studies was assessed by the Newcastle Ottawa Scale (NOS) and the Agency for Healthcare Research Quality (AHRQ). In order to evaluate the sexual function between the stoma group and the non-stoma group, mean values and standard deviation were pooled for scores in questionnaires, and odds ratio and 95% confidence intervals were pooled for self-designed problems. Results were shown in forest plots; Egger's test and the trim and fill analysis were used for assessing the publication bias. All the data analyses above were performed by STATA 16.0 software. RESULTS: Six cohort studies and three cross-sectional studies were included for this pooling up analysis. As for the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C38), male patients with stomas had more sexual problems (mean differences = 0.32, 95% confidence intervals = 0.01 to 0.63, I2 = 67.80%, P = 0.05); however, other indicators including sexual functioning, sexual enjoyment, and female sexual problems had little difference between the two groups. As for other questionnaires and problems, stoma did not have an impact on sexual function. CONCLUSION: The stoma after surgery was not significantly associated with the sexual function of female patients with colorectal cancer and was associated with worse scores on only sexual problems for males.

Enhanced recovery after colorectal surgery is a safe and effective pathway for older patients: a pooling up analysis.

PURPOSE: The current study aimed to explore the efficacy and safety of Enhanced Recovery after surgery (ERAS) in older patients undergoing colorectal surgery. METHODS: Three databases including PubMed, Embase, Medline, and the Cochrane Library were used for searching eligible studies on Jun 8th,2022. To evaluate the effect of ERAS, we focused on the short-term outcomes including postoperative complications and recovery. Subgroup analysis was also conducted for patients undergoing colorectal cancer (CRC) surgery. All the data processing and analyses were carried out by Stata (V.16.0) software. RESULTS: Finally, there were fourteen studies involving 5961 patients enrolled in this study. As for surgical outcomes, we found that the older group had more overall complications (OR = 1.41, I2 = 36.59%, 95% CI = 1.20 to 1.65, P = 0.00), more obstruction (OR = 1.462, I2 = 0.00%, 95% CI = 1.037 to 2.061, P = 0.0304), more respiratory complications (OR = 1.721, I2 = 0.00%, 95% CI = 1.177 to 2.515, P = 0.0051), more cardiovascular complications (OR = 3.361, I2 = 57.72%, 95% CI = 1.072 to 10.542, P = 0.0377), more urinary complications (OR = 1.639, I2 = 37.63%, 95% CI = 1.168 to 2.299, P = 0.0043), less readmission (OR = 0.662, I2 = 44.48%, 95% CI = 0.484 to 0.906, P = 0.0100), higher mortality (OR = 0.662, I2 = 44.48%, 95% CI = 0.484 to 0.906, P = 0.0100), and longer overall survival (OS) (HR = 1.21, I2 = 0.00%, 95% CI = 0.566 to 1.859, P = 0.0002)). Subgroup analysis also found that older CRC patients had a higher risk of overall complications (OR = 1.37, I2 = 37.51%, 95% CI = 1.06 to 1.78, P < 0.05). CONCLUSION: Although ERAS could accelerate postoperative recovery and reduce postoperative complications, older patients who received ERAS still had higher complication incidence than younger patients. Although the proportion of re-hospitalizations was lower and the OS was better, doctors could not rely too much on ERAS. More measures were needed to improve the outcomes of colorectal surgery in older patients.

A comparative study on laparoscopic and open surgical approaches for perforated peptic ulcer repair: efficacy and outcomes analysis.

PURPOSE: This study aimed to compare the clinical outcomes of the clinical outcomes of laparoscopic and open sutures for peptic ulcer perforation (PPU). MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies from inception to March 31, 2023. Odds ratios (OR) and 95% confidence intervals (Cl) were also calculated. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies. This study was performed using the Stata (V.16.0) software. RESULTS: A total of 29 studies involving 17,228 patients were included in this study. In terms of postoperative outcomes, the laparoscopic group had a shorter postoperative hospital stay (MD = -0.29, 95%CI = -0.44 to -0.13, P = 0.00), less blood loss (MD = -0.45, 95%CI = -0.82 to -0.08, P = 0.02), fewer wound infection (OR = 0.20, 95%CI = 0.17 to 0.24, P = 0.00), fewer pneumonia (OR = 0.59, 95%CI = 0.41 to 0.87, P = 0.01), fewer respiratory complications (OR = 0.26, 95%CI = 0.13 to 0.55, P = 0.00) and lower postoperative morbidity (OR = 0.51, 95%CI = 0.33 to 0.78, P = 0.00). The laparoscopic group had a lower mortality rate (OR = 0.36, 95%CI = 0.27 to 0.49, P = 0.00) than the open group. We also found that the laparoscopic group had a higher overall complication rate than the open group (OR = 0.45, 95%CI = 0.34 to 0.60, P = 0.00). CONCLUSION: Laparoscopic repair was associated with a lower risk of mortality than open repair in patients with PPU. Laparoscopic repair may be a better option in patients with PPU.

The predictive value of advanced lung cancer inflammation index for short-term outcomes and prognosis of colorectal cancer patients who underwent radical surgery.

PURPOSE: The purpose of this study was to investigate the predictive value of advanced lung cancer inflammation index (ALI) for short-term outcomes and prognosis of colorectal cancer (CRC) patients who underwent radical surgery. METHODS: CRC patients who underwent radical resection were included from Jan 2011 to Jan 2020 in our single clinical centre. Short-term outcomes, overall survival (OS), and disease-free survival (DFS) were compared in different groups. Cox analysis was conducted to identify independent risk factors for OS and DFS. RESULTS: A total of 4010 patients who underwent radical CRC surgery were enrolled in the current study. As a result, the low ALI group had longer operation time (p = 0.02), more intra-operative blood loss (p < 0.01), longer postoperative hospital stay (p < 0.01), and more overall complications (p < 0.01). Moreover, ALI (p < 0.01, OR = 0.679, 95% CI = 0.578-0.798) was an independent risk factor for overall complications. As for survival, the low ALI group had worse OS in all TNM stages (p < 0.01), stage II (p < 0.01) and stage III (p < 0.01). Similarly, the low ALI group had worse DFS in all TNM stages (p < 0.01), stage II (p < 0.01), and stage III (p < 0.01). In Cox analysis, ALI was an independent risk factors for OS (p < 0.01, HR = 0.707, 95% CI = 0.589-0.849) and DFS (p < 0.01, HR = 0.732, 95% CI = 0.622-0.861). CONCLUSION: Lower ALI was associated with more postoperative complications, worse OS, and DFS for CRC patients who underwent radical surgery. Furthermore, ALI was an independent risk factor for overall complications, OS, and DFS. Surgeons should pay close attention to patients with low ALI before surgery and make clinical strategies cautiously.

Comparison of endoscopic submucosal dissection versus surgery for early gastric cancer in the elderly: a pooled analysis.

PURPOSE: The aim of this study was to investigate whether there was a difference in overall survival (OS) between elderly patients with early gastric cancer (EGC) who underwent endoscopic submucosal dissection (ESD) and those who underwent surgery. METHODS: Four databases including PubMed, Embase, the Cochrane Library and CKNI were searched on March 20, 2023. The characteristics of the studies and the baseline information of the patients, including their medical histories, postoperative data, and prognoses, were recorded. Odds ratios (ORs) or mean differences (MDs), and 95% confidence intervals (CIs) were pooled up to calculate baseline information and postoperative information. Hazard ratios (HRs) and 95% CIs were used to calculate the prognosis of the patients. Stata V16.0 software was used for the data analysis. RESULTS: A total of eight studies involving 2334 patients were included for the data analysis in this study. After pooling up the data, we found that the ESD group had lower Eastern Cooperative Oncology Groupprevious (ECOG) scores (OR = 0.33, 95% CI = 0.17 to 0.65, I2 = 59.69%, P = 0.00 < 0.05) than the surgery group. There were significant differences in the operation time (MD = -3.38, 95% CI = -5.19 to -1.57, I2 = 98.31%, P = 0.00 < 0.05), length of hospital stay (MD = -3.01, 95% CI = -4.81 to -1.20, I2 = 98.83%, P = 0.00 < 0.05) and hospitalization expenses (MD = -2.67, 95% CI = -3.59 to -1.75, I2 = 93.21%, P = 0.00 < 0.05) between the two groups. The ESD group had a lower OS rate (HR = 2.81, 95% CI = 2.20 to 3.58, I2 = 12.28%, P = 0.00 < 0.05). CONCLUSION: Elderly patients with EGC who underwent ESD had a significantly worse OS rate than those who underwent surgery. If the patient's condition was suitable, surgery was still recommended for these patients.

The advanced lung cancer inflammation index is a prognostic factor for gastrointestinal cancer patients undergoing surgery: a systematic review and meta-analysis.

BACKGROUND: The advanced lung cancer inflammation index (ALI) is a comprehensive assessment indicator that can reflect inflammation and nutrition conditions. However, there are some controversies about whether ALI is an independent prognostic factor for gastrointestinal cancer patients undergoing surgical resection. Thus, we aimed to clarify its prognostic value and explore the potential mechanisms. METHODS: Four databases including PubMed, Embase, the Cochrane Library, and CNKI were used for searching eligible studies from inception to June 28, 2022. All gastrointestinal cancers, including colorectal cancer (CRC), gastric cancer (GC), esophageal cancer (EC), liver cancer, cholangiocarcinoma, and pancreatic cancer were enrolled for analysis. We focused on prognosis most in the current meta-analysis. Survival indicators, including overall survival (OS), disease-free survival (DFS), and cancer-special survival (CSS) were compared between the high ALI group and the low ALI group. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was submitted as a supplementary document. RESULTS: We finally included fourteen studies involving 5091 patients in this meta-analysis. After pooling the hazard ratios (HRs) and 95% confidence intervals (CIs), ALI was found to be an independent prognostic factor for both OS (HR = 2.09, I2 = 92%, 95% CI = 1.53 to 2.85, P < 0.01), DFS (HR = 1.48, I2 = 83%, 95% CI = 1.18 to 1.87, P < 0.01), and CSS (HR = 1.28, I2 = 1%, 95% CI = 1.02 to 1.60, P = 0.03) in gastrointestinal cancer. After subgroup analysis, we found that ALI was still closely related to OS for CRC (HR = 2.26, I2 = 93%, 95% CI = 1.53 to 3.32, P < 0.01) and GC (HR = 1.51, I2 = 40%, 95% CI = 1.13 to 2.04, P = 0.006) patients. As for DFS, ALI also has a predictive value on the prognosis of CRC (HR = 1.54, I2 = 85%, 95% CI = 1.14 to 2.07, P = 0.005) and GC (HR = 1.37, I2 = 0%, 95% CI = 1.09 to 1.73, P = 0.007) patients. CONCLUSION: ALI affected gastrointestinal cancer patients in terms of OS, DFS, and CSS. Meanwhile, ALI was a prognostic factor both for CRC and GC patients after subgroup analysis. Patients with low ALI had poorer prognoses. We recommended that surgeons should perform aggressive interventions in patients with low ALI before the operation.

Effects of preoperative bicarbonate and lactate levels on short-term outcomes and prognosis in elderly patients with colorectal cancer.

PURPOSE: The aim of this study was to analyze the effect of preoperative bicarbonate and lactate levels (LL) on the short-term outcomes and prognosis in elderly (≥ 65 years) patients with colorectal cancer (CRC). METHODS: We collected the information of CRC patients from Jan 2011 to Jan 2020 in a single clinical center. According to the results of preoperative blood gas analysis, we divided patients into the higher/lower bicarbonate group and the higher/lower lactate group, and compared their baseline information, surgery-related information, overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 1473 patients were included in this study. Comparing the clinical data of the higher/lower bicarbonate group and the higher/lower lactate group, the lower group were older (p < 0.01), had higher rates of coronary heart disease (CHD) (p = 0.025), a higher proportion of colon tumors (p < 0.01), larger tumor size (p < 0.01), higher rates of open surgery (p < 0.01), more intraoperative blood loss (p < 0.01), higher overall complications (p < 0.01) and 30-day deaths (p < 0.01). The higher LL patients had more male patients (p < 0.01), higher body mass index (BMI) (p < 0.01) and drinking rates (p = 0.049), higher rates of type 2 diabetes mellitus (T2DM) (p < 0.01) and lower rates of open surgery (p < 0.01). In multivariate analysis, age (p < 0.01), BMI (p = 0.036), T2DM (p = 0.023), and surgical methods (p < 0.01) were independent risk factors of overall complications. The independent risk factors for OS included age (p < 0.01), tumor site (p = 0.014), tumor stage (p < 0.01), tumor size (p = 0.036), LL (p < 0.01), and overall complications (p < 0.01). The independent risk factors of DFS included age (p = 0.012), tumor site (p = 0.019), tumor stage (p < 0.01), LL (p < 0.01), and overall complications (p < 0.01). CONCLUSION: Preoperative LL significantly affected postoperative OS and DFS of CRC patients, but bicarbonate might not affect the prognosis of CRC patients. Therefore, surgeons should actively focus on and adjust the LL of patients before surgery.

A Cerium Organic Framework with {Cu2I2} Cluster and {Cu2I2}n Chain Modules: Structure and Fluorescence Sensing Properties.

In this work, a copper iodine module bearing a coordination polymer (CP) with a formula of [(Cu2I2)2Ce2(INA)6(DMF)3]·DMF (1, HINA = isonicotinic acid, DMF = N,N'-dimethyl formamide) is presented. The title compound features a three dimensional (3D) structure, in which the {Cu2I2} cluster and {Cu2I2}n chain modules are coordinated by N atoms from a pyridine ring in INA- ligands, while the Ce3+ ions are bridged by the carboxylic groups of INA- ligands. More importantly, compound 1 exhibits an uncommon red fluorescence (FL) with a single emission band maximized at 650 nm belonging to near infrared (NIR) luminescence. The temperature dependent FL measurement was applied to investigate the FL mechanism. Remarkably, 1 could be used as a FL sensor to cysteine and the nitro-bearing explosive molecule of trinitropheno (TNP) with high sensitivity, demonstrating its potential FL sensing applications for biothiol and explosive molecules.

A Soluble Porous Coordination Polymer for Fluorescence Sensing of Explosives and Toxic Anions under Homogeneous Environment.

In the past decades, porous coordination polymers (PCPs) based fluorescent (FL) sensors have received intense attention due to their promising applications. In this work, a soluble Zn-PCP is presented as a sensitive probe towards explosive molecules, chromate, and dichromate ions. In former reports, PCP sensors were usually ground into fine powders and then dispersed in solvents to form FL emulsion for sensing applications. However, their insoluble characters would cause the sensing accuracy which is prone to interference from environmental effects. While in this work, the as-made PCP could be directly soluble in organic solvents to form a clear solution with bright blue emission, representing the first soluble PCP based fluorescence sensor to probe explosive molecules under a homogeneous environment. Moreover, the FL PCP solution also shows sensitive detection behaviors towards the toxic anions of CrO42- and Cr2O72-, which exhibit a good linear relationship between the fluorescence intensity of Zn-PCP and the concentrations of both analytes. This work provides a reference for designing task-specific PCP sensors utilized under a homogeneous environment.

Structural Evolution and Properties of Praseodymium Antimony Oxochlorides Based on a Chain-like Tertiary Building Unit.

Unveiling the structural evolution of single-crystalline compounds based on certain building units may help greatly in guiding the design of complex structures. Herein, a series of praseodymium antimony oxohalide crystals have been isolated under solvothermal conditions via adjusting the solvents used, that is, [HN(CH2CH3)3][FeII(2,2'-bpy)3][Pr4Sb12O18Cl15]·EtOH (1) (2,2'-bpy = 2,2'-bipyridine), [HN(CH2CH3)3][FeII(2,2'-bpy)3]2[Pr4Sb12O18Cl14)2Cl]·N(CH2CH3)3·2H2O (2), and (H3O)[Pr4Sb12O18Cl12.5(TEOA)0.5]·2.5EtOH (3) (TEOA = mono-deprotonated triethanolamine anion). Single-crystal X-ray diffraction analysis revealed that all the three structures feature an anionic zig-zag chain of [Pr4Sb12O18Cl15-x]n as the tertiary building unit (TBU), which is formed by interconnections of praseodymium antimony oxochloride clusters (denoted as {Pr4Sb12}) as secondary building units. Interestingly, different arrangements or linkages of chain-like TBUs result in one-dimensional, two-dimensional layered, and three-dimensional structures of 1, 2, and 3, respectively, thus demonstrating clearly the structural evolution of metal oxohalide crystals. The title compounds have been characterized by elemental analysis, powder X-ray diffraction, thermogravimetric analysis, and UV-Vis spectroscopy, and the photodegradation for methyl blue in an aqueous solution of compound 1 has been preliminarily studied. This work offers a way to deeply understand the assembly process of intricate lanthanide-antimony(III) oxohalide structures at the atomic level.

Luminescence Enhancement and Temperature Sensing Properties of Hybrid Bismuth Halides Achieved via Tuning Organic Cations.

Bismuth-halide-based inorganic-organic hybrid materials (Bi-IOHMs) are desirable in luminescence-related applications due to their advantages such as low toxicity and chemical stability. Herein, two Bi-IOHMs of [Bpy][BiCl4(Phen)] (1, Bpy = N-butylpyridinium, Phen = 1,10-phenanthroline) and [PP14][BiCl4(Phen)]·0.25H2O (2, PP14 = N-butyl-N-methylpiperidinium), containing different ionic liquid cations and same anionic units, have been synthesized and characterized. Single-crystal X-ray diffraction reveals that compounds 1 and 2 crystallize in the monoclinic space group of P21/c and P21, respectively. They both possess zero-dimensional ionic structures and exhibit phosphorescence at room temperature upon excitation of UV light (375 nm for 1, 390 nm for 2), with microsecond lifetime (24.13 µs for 1 and 95.37 µs for 2). Hirshfeld surface analysis has been utilized to visually exhibit the different packing motifs and intermolecular interactions in 1 and 2. The variation in ionic liquids makes compound 2 have a more rigid supramolecular structure than 1, resulting in a significant enhancement in photoluminescence quantum yield (PLQY), that is, 0.68% for 1 and 33.24% for 2. In addition, the ratio of the emission intensities for compounds 1 and 2 shows a correlation with temperature. This work provides new insight into luminescence enhancement and temperature sensing applications involving Bi-IOHMs.

The deacetylation of Foxk2 by Sirt1 reduces chemosensitivity to cisplatin.

In multiple types of cancer, decreased tumour cell apoptosis during chemotherapy is indicative of decreased chemosensitivity. Forkhead box K2 (FOXK2), which is essential for cell fate, regulates cancer cell apoptosis through several post-translational modifications. However, FOXK2 acetylation has not been extensively studied. Here, we evaluated the effects of sirtiun 1 (SIRT1) on FOXK2 deacetylation. Our findings demonstrated that SIRT1 inhibition increased FOXK2-induced chemosensitivity to cisplatin and that K223 in FOXK2 was acetylated. Furthermore, FOXK2 K223 deacetylation reduced chemosensitivity to cisplatin in vitro and in vivo. Mechanistically, FOXK2 was acetylated by the acetyltransferase cAMP response element binding protein and deacetylated by SIRT1. Furthermore, cisplatin attenuated the interaction between FOXK2 and SIRT1. Cisplatin or SIRT1 inhibition enhanced FOXK2 acetylation, thereby reducing the nuclear distribution of FOXK2. Additionally, FOXK2 K223 acetylation significantly affected the expression of cell cycle-related and apoptosis-related genes in cisplatin-stimulated cancer cells, and FOXK2 K223 hyperacetylation promoted mitotic catastrophe, which enhanced chemosensitivity to cisplatin. Overall, our results provided insights into the mechanisms of SIRT1-mediated FOXK2 deacetylation, which was involved in chemosensitivity to cisplatin.

Preoperative hypokalemia can increase complications after colorectal cancer surgery: a propensity score matching analysis.

BACKGROUND: Whether hypokalemia can affect the short-term outcomes of CRC patients after radical surgery remains unclear. The purpose of this study was to investigate the impact of preoperative hypokalemia on the short-term outcomes for colorectal cancer (CRC) patients who underwent radical CRC surgery using propensity score matching (PSM). METHODS: We retrospectively enrolled consecutive CRC patients from Jan 2011 to Dec 2021 in a single-center hospital. Hypokalemia was defined as a serum potassium concentration < 3.5 mmol/L. The short-term outcomes were compared between the hypokalemia group and the normal blood potassium group. In addition, univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for overall complications. RESULTS: A total of 6183 CRC patients who underwent radical surgery were included in this study, of whom 390 (6.3%) patients were diagnosed with hypokalemia before surgery. After 1:1 ratio PSM, there were 390 patients in the hypokalemia group and in the normal potassium group. No significant difference was found between the two groups after PSM in terms of baseline information (p > 0.05). Regarding short-term outcomes, the hypokalemia group had a longer hospital stay (p = 0.028), a higher proportion of overall complications (p = 0.048) and a higher incidence of postoperative pneumonia (p = 0.008) after PSM. Moreover, hypokalemia (p = 0.036, OR = 1.291, 95% CI = 1.017-1.639) was an independent risk factor for overall complications. CONCLUSION: Preoperative hypokalemia could increase complications after CRC surgery and prolong the hospital stay. Moreover, preoperative hypokalemia was an independent risk factor for overall complications.

Bufadienolides from the Eggs of the Toad Bufo bufo gargarizans and Their Antimelanoma Activities.

Toads produce potent toxins, named bufadienolides, to defend against their predators. Pharmacological research has revealed that bufadienolides are potential anticancer drugs. In this research, we reported nine bufadienolides from the eggs of the toad Bufo bufo gargarizans, including two new compounds (1 and 3). The chemical structures of 1 and 3, as well as of one previously reported semisynthesized compound (2), were elucidated on the basis of extensive spectroscopic data interpretation, chemical methods, and X-ray diffraction analysis. Compound 1 is an unusual 19-norbufadienolide with rearranged A/B rings. A biological test revealed that compounds 2 and 4-8 showed potent cytotoxic activities toward human melanoma cell line SK-MEL-1 with IC50 values less than 1.0 µM. A preliminary mechanism investigation revealed that the most potent compound, 8, could induce apoptosis via PARP cleavage, while 5 and 6 significantly suppressed angiogenesis in zebrafish. Furthermore, an in vivo biological study showed that 5, 6, and 8 inhibit SK-MEL-1 cell growth significantly.