Analysis of causes and prognostic impact of tube occlusion during hyperthermic intraperitoneal chemotherapy for appendiceal pseudomyxoma peritonei.

BACKGROUND: Appendiceal pseudomyxoma peritonei (PMP), a rare tumor from mucinous appendiceal origins, is treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). However, tubing blockages during HIPEC treatment pose a common challenge, impeding the smooth progression of therapy. Few studies to date have explored the incidence and risk factors of tube occlusion during HIPEC in patients with appendiceal PMP, as well as its adverse impact on postoperative complications. METHODS: From October 2017 to June 2023, a total of 80 patients with appendiceal PMP undergoing combined CRS and HIPEC were included in this study. Tubing blockage events were strictly defined, with patients experiencing blockages during HIPEC treatment allocated to the study group, while those with unobstructed perfusion were assigned to the control group. A comparative analysis was conducted between the two groups regarding post-HIPEC health assessments and occurrence of complications. Risk factors for luminal occlusion during closed HIPEC procedures were identified through univariate and multivariate analysis of data from 303 HIPEC treatments. RESULTS: Tubing blockages occurred in 41 patients (51.3%). The study group experienced prolonged gastrointestinal decompression time (4.1 ± 3.0 vs. 2.5 ± 1.7 days, P = 0.003) and prolonged time to bowel movement (6.1 ± 2.3 vs. 5.1 ± 1.8 days, P = 0.022) compared to the control group. There was no significant difference in the incidence of complications between the two groups. The 1-year survival rate postoperatively was 97%, and the 3-year survival rate was 81%, with no association found between tubing blockage and poorer survival. Additionally, In 303 instances of HIPEC treatment among these 80 patients, tube occlusion occurred in 89 cases (89/303, 29.4%). Multivariable logistic regression analysis revealed age, diabetes, hypertension, and pathology as independent risk factors for tube occlusion. CONCLUSION: Tubing blockages are a common occurrence during HIPEC treatment, leading to prolonged postoperative gastrointestinal functional recovery time. When patients are elderly and have concomitant hypertension and diabetes, along with a histological type of low-grade mucinous tumor, the risk of tube occlusion increases. However, this study did not find a significant correlation between tubing blockage and the incidence of postoperative complications or overall patient survival.

Prognostic Characteristics of Patients With Colorectal Cancer Who Have Benign Mesenteric Lymph Node Enlargement: A Multi-institutional Cohort Study.

BACKGROUND: The characteristics of patients with colorectal cancer who have benign mesenteric lymph node enlargement are not well documented. OBJECTIVE: The aim of this study is to assess the clinical and prognostic significance of benign mesenteric lymph node enlargement in patients with colorectal cancer. DESIGN: This is a prospective cohort study. SETTING: This study was conducted at multitertiary institutions. PATIENTS: We included 601 patients with stage 0, I, and II colorectal cancer in Tianjin, Shandong, and Zhejiang from January 2010 to April 2014. Patients underwent curative surgery and were separated into 2 groups by the presence of benign mesenteric lymph node enlargement: the enlargement group (n = 275) and the control group (n = 326). MAIN OUTCOME MEASURES: Univariate log rank and multivariate Cox regression analyses were constructed to identify risk factors for recurrence and mortality. RESULTS: The risk of recurrence in the enlargement group after curative resection was significantly lower than in the control group, with the 1-, 3-, and 5-year disease-free survival rates being 97.1%, 91.6%, and 86.9% in the enlargement group and 95.7%, 86.2%, and 78.2% in the control group (p = 0.004). The postoperative 1-, 3-, and 5-year overall survival rates were 99.6%, 94.9%, and 90.5% in the enlargement group and 99.4%, 91.4%, and 82.1% in the control group (p = 0.001). Patients in the enlargement group had a higher percentage of patients at a younger age, family tumor history, right-sided tumors, and larger tumor size compared with the control group. For patients in the enlargement group, no significant correlation was observed between the number of enlarged lymph nodes and disease-free survival or overall survival (p = 0.113 and 0.386). Adjusted Cox regression model showed that benign mesenteric lymph node enlargement was an independent prognostic risk factor for both disease-free survival (HR, 0.587; 95% CI, 0.399-0.861; p = 0.007) and overall survival (HR, 0.506; 95% CI, 0.328-0.779; p = 0.002). LIMITATIONS: No immunological results could be compared with clinicopathological findings. CONCLUSIONS: The study indicates that benign mesenteric lymph node enlargement can be a useful positive factor in predicting recurrence and long-term survival concerning patients with colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B785. CARACTERSTICAS PRONSTICAS DE LOS PACIENTES PORTADORES DE CNCER COLORRECTAL CON AGRANDAMIENTO BENIGNO DE LOS GANGLIOS LINFTICOS MESENTRICOS UN ESTUDIO DE COHORTE MULTIINSTITUCIONAL: ANTECEDENTES:Las características de los pacientes portadores de cáncer colorrectal con agrandamiento benigno de los ganglios linfáticos mesentéricos no se encuentran bien documentados.OBJETIVO:El objetivo de este estudio es evaluar la importancia clínica y pronóstica del agrandamiento benigno de los ganglios linfáticos mesentéricos en pacientes con cáncer colorrectal.DISEÑO:Este es un estudio de cohorte de tipo prospectivo.AJUSTE:Este estudio se llevó a cabo en instituciones de educación superior.PACIENTES:Incluimos a 601 pacientes con cáncer colorrectal en estadio 0, I, II en Tianjin, Shandong y Zhejiang desde enero de 2010 hasta abril de 2014. Los pacientes fueron sometidos a cirugía curativa y fueron separaron en dos grupos tomando en cuenta la presencia del agrandamiento benigno de los ganglios linfáticos mesentéricos: grupo con agrandamiento (n = 275) y grupo control (n = 326).PRINCIPALES MEDIDAS DE RESULTADO:Se construyeron análisis de rango logarítmico de una variante y de regresión de Cox con variante múltiple para identificar los factores de riesgo de recurrencia y mortalidad.RESULTADOS:El riesgo de recurrencia en el grupo con agrandamiento tras la resección curativa fue significativamente menor que en el grupo de control, con tasas de periodo libre de enfermedad a los 1, 3 y 5 años de 97,1, 91,6, y 86,9% en el grupo de agrandamiento y con tasas de 95,7, 86,2, y 78,2% en el grupo control respectivamente (p = 0,004). Las tasas postoperatorias de supervivencia general a los 1, 3 y 5 años fueron 99,6, 94,9, y 90,5% en el grupo de agrandamiento y de 99,4, 91,4, y 82,1% en el grupo de control, respectivamente (p = 0,001). Los pacientes del grupo con agrandamiento tenían un porcentaje más elevado de menor edad, antecedente familiar tumoral, tumores del lado derecho y de mayor tamaño tumoral con respecto al grupo de control. Para los pacientes con agrandamiento, no se observó una correlación significativa entre el número de ganglios linfáticos agrandados y el periodo libre de enfermedad o la supervivencia general (p = 0,113 y 0,386). El modelo de regresión de Cox ajustado mostró que el agrandamiento benigno de los ganglios linfáticos mesentéricos era un factor de riesgo pronóstico independiente tanto para la supervivencia libre de enfermedad (cociente de riesgo 0,587; IC del 95%: 0,399-0,861; p = 0,007) como para la supervivencia global (cociente de riesgo 0,506; IC del 95%: 0,328- 0,779; p = 0,002).LIMITACIONES:No fue posible comparar los resultados inmunológicos con los hallazgos clínico-patológicos.CONCLUSIONES:El estudio indica que el agrandamiento benigno de los ganglios linfáticos mesentéricos puede ser un factor positivo útil para predecir la recurrencia y la supervivencia a largo plazo en pacientes con cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B785. (Traducción-Dr. Osvaldo Gauto).

Hsa_circ_0026416 promotes proliferation and migration in colorectal cancer via miR-346/NFIB axis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been confirmed to be key regulators of many diseases. With many scholars devoted to studying the biological function and mechanism of circRNAs, their mysterious veil is gradually being revealed. In our research, we explored a new circRNA, hsa_circ_0026416, which was identified as upregulated in CRC with the largest fold change (logFC = 3.70) of the evaluated circRNAs via analysing expression profiling data by high throughput sequencing of members of the GEO dataset (GSE77661) to explore the molecular mechanisms of CRC. METHODS: qRT-PCR and western blot analysis were utilized to assess the expression of hsa_circ_0026416, miR-346 and Nuclear Factor I/B (NFIB). CCK-8 and transwell assays were utilized to examine cell proliferation, migration and invasion in vitro, respectively. A luciferase reporter assay was used to verify the combination of hsa_circ_0026416, miR-346 and NFIB. A nude mouse xenograft model was also utilized to determine the role of hsa_circ_0026416 in CRC cell growth in vivo. RESULTS: Hsa_circ_0026416 was markedly upregulated in CRC patient tissues and plasma and was a poor prognosis in CRC patients. In addition, the area under the curve (AUC) of hsa_circ_0026416 (0.767) was greater than the AUC of CEA (0.670), CA19-9 (0.592) and CA72-4 (0.575). Functionally, hsa_circ_0026416 promotes cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, hsa_circ_0026416 may function as a ceRNA via competitively absorbing miR-346 to upregulate the expression of NFIB. CONCLUSIONS: In summary, our findings demonstrate that hsa_circ_0026416 is an oncogene in CRC. Hsa_circ_0026416 promotes the progression of CRC via the miR-346/NFIB axis and may represent a potential biomarker for diagnosis and therapy in CRC.

Post-therapy pathologic tumor volume predicts survival in gastric cancer patients who underwent neoadjuvant chemotherapy and gastrectomy.

BACKGROUND: To demonstrate that post-therapy pathological tumor volume (ypTV) should be considered as an independent prognostic factor in advanced gastric cancer (GC) patients who underwent neoadjuvant chemotherapy (NAC) and gastrectomy. METHODS: A total of 253 GC patients who received gastrectomy between January 2010 and December 2016 in our hospital were enrolled in this study. Clinicopathologic factors were evaluated using univariable and multivariable analysis. ypTV was calculated using π* (tumor diameter/2)2 *tumor invasion depth (cm3). RESULTS: Cut-point survival analysis demonstrated that the appropriate cut-offs for ypTV were 3, 6, 10, and 19 (cm3). Patients with tumor volumes of 0-3.0, 3.1-6.0, 6.1-10.0, 10.1-19.0, ≥19.1 cm3 were defined as ypTV1, 2, 3, 4a and 4b. Using multivariable analysis, the tumor volume (ypTV stage, P < 0.05), ypN stage (P < 0.05), response to NAC (P < 0.05), vascular invasion (P < 0.05) and ypTvNM staging (P < 0.05) were independent prognostic factors. Kaplan-Meier analysis demonstrated that the 8th AJCC/UICC ypTNM staging was not a significant predictor for survival (P > 0.05); however, our newly defined ypTvNM staging was a significant predictor for survival (P < 0.05). CONCLUSIONS: ypTV should be considered as an independent prognostic factor for GC patients after NAC. ypTvNM staging should be recommended to improve the accuracy of prognostic prediction for GC patients who received NAC plus gastrectomy.

Hesperetin derivatives: Synthesis and anti-inflammatory activity.

Sixteen novel hesperetin derivatives containing Mannich base moiety were designed and synthesized and their anti-inflammatory activities were evaluated by inhibiting tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in mouse RAW264.7 macrophages. Compounds 3a-3k showed better hydrophilic, while compounds 3l-3p with aromatic groups was hydrophobic. The anti-inflammatory activity of title compounds was correlated with logP values, among them, compounds 3c, 3e and 3i with minus logP values exhibited best anti-inflammatory activity through decreasing both IL-6 and TNF-α. Furthermore, the expression of LPS-induced notch1 and inos was reduced by compounds 3c, 3e, and 3i, and compound 3e attenuated LPS-induced inos protein levels in a dose-dependent manner.

New coumarin derivatives: design, synthesis and use as inhibitors of hMAO.

A series new 2H-chromene-3-carboxamides (4a-4i) and S-2H-chromene-3-carbothioates (5j-5t) were synthesized and evaluated as monoamine oxidase A and B inhibitors. Among them, compound 5k (IC50=0.21µM, IC50 iproniazid=7.65µM) showed the most activity and higher MAO-B selectivity (189.2-fold vs 1-fold) with respect to the MAO-A isoform. The need to clarify at a 3D level some important molecular aspects of discussed SAR, we undertaked a number of docking simulations to better assess. The steric effect was analyzed interms of both posing and scoring by investigating the nature of the binding interactions. The docking results of active compound 5k with hMAO-B complex indicated that conserved residue ILE 199 was important for ligand binding via Sigma-Pi interaction.

Surface-modified titanium and titanium-based alloys for improved osteogenesis: A critical review.

As implantable materials, titanium, and its alloys have garnered enormous interest from researchers for dental and orthopedic procedures. Despite their success in wide clinical applications, titanium, and its alloys fail to stimulate osteogenesis, resulting in poor bonding strength with surrounding bone tissue. Optimizing the surface topology and altered compositions of titanium and titanium-based alloys substantially promotes peri-implant bone regeneration. This review summarizes the utilization and importance of various osteogenesis components loaded onto titanium and its alloys. Further, different surface-modification methods and the release efficacy of loaded substances are emphasized. Finally, we summarize the article with prospects. We believe that further investigation studies must focus on identifying novel loading components, exploring various innovative, optimized surface-modification methods, and developing a sustained-release system on implant surfaces to improve peri-implant bone formation.

N-Coordinated Iridium-Molybdenum Dual-Atom Catalysts Enabling Efficient Bifunctional Hydrogen Electrocatalysis.

Achieving effective hydrogen evolution/oxidation reaction (HER/HOR) across a wide pH span is of critical importance in unlocking the full potential of hydrogen energy but remains intrinsically challenging. Here, we engineer the N-coordinated Ir-Mo dual atoms on a carbon matrix by ultrafast high-temperature sintering, creating an efficient bifunctional electrocatalyst for both HER and HOR in both acidic and alkaline electrolytes. The optimized catalyst, Ir-Mo DAC/NC, demonstrates exceptional performance, with a significantly reduced HER overpotential of 11.3 mV at 10 mA/cm2 and a HOR exchange current (i0,m) of 3972 mA/mgIr in acidic conditions, surpassing the performance of Pt/C and Ir/C catalysts. In alkaline conditions, Ir-Mo DAC/NC also outperforms Pt/C, as evidenced by its low HER overpotential of 23 mV at 10 mA/cm2 and a high i0,m of 1308 mA/mgIr. Furthermore, our catalyst exhibits remarkable stability in both acidic and alkaline environments. DFT calculations results reveal that the superior electrochemical performance of Ir-Mo DAC/NC arises from the electronic synergy between Ir and Mo pairs, which regulates the interaction between the intermediates and active sites. These findings present a promising strategy for the development of dual-atom catalysts (DACs), with potential applications in the polymer fuel cells and water electrolyzers.

The intramolecular SN2 reaction tautomeric ent-Kauranoids isolated from the aerial parts of Isodon amethystoides.

As our ongoing searching for the bioactive natural terpenoids, nine ent-kauranoids (1-9), including three previously undescribed ones (1, 2, and 9), were isolated from the aerial parts of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic data analysis, including NMR, MS, and ECD. Compounds 1 and 2 were a pair of tautomeric compounds, which was confirmed by the HPLC analysis and low temperature NMR testing. The underlying mechanism of the tautomer was proposed as an intramolecular SN2 reaction, which was explained by quantum chemical calculation. The HOMO-LUMO gap and the free energy revealed the spontaneous of the tautomeric of the 1 and 2. Additionally, the similar phenomena were also found in the two groups of known compounds 3 and 4 and 6 and 7, respectively. Apart from the tautomer, compounds 3 and 4 can be hydrolyzed into 5 through ester hydrolysis in CDCl3, while compounds 6, 7 can be hydrolyzed into 8 through ester hydrolysis. These phenomena were also confirmed through HPLC analysis and low temperature nuclear magnetic resonance tests and the mechanism was studied using quantum chemical calculation.

Chitosan/esterified chitin nanofibers nanocomposite films incorporated with rose essential oil: Structure, physicochemical characterization, antioxidant and antibacterial properties.

Active films were developed based on chitosan, esterified chitin nanofibers and rose essential oil (REO). The joint effects of chitin nanofibers and REO on structure and physicochemical properties of chitosan film were investigated. Scanning electron microscopy and Fourier transform infrared spectroscopy showed that the chitin nanofibers and REO had significant effects on the morphology and chemical structure of chitosan composite films. The negatively charged esterified chitin nanofibers formed a compact network structure through intermolecular hydrogen bonding and electrostatic interactions with the positively charged chitosan matrix. Chitin nanofibers and REO synergistically enhanced the water resistance, mechanical properties and UV resistance of chitosan-based films, but the addition of REO increased the oxygen permeability. Furthermore, the addition of REO enhanced the inhibition of ABTS and DPPH free radicals and microorganisms by chitosan-based film. Therefore, chitosan/chitin nanofiber-based active films containing REO as food packaging materials can potentially provide protection to extend food shelf life.

Sulfur-fluoride exchange (SuFEx)-enabled lead discovery of AChE inhibitors by fragment linking strategies.

SuFEx click chemistry has been a method for the rapid synthesis of functional molecules with desirable properties. Here, we demonstrated a workflow that allows for in situ synthesis of sulfonamide inhibitors based on SuFEx reaction for high-throughput testing of their cholinesterase activity. According to fragment-based drug discovery (FBDD), sulfonyl fluorides [R-SO2F] with moderate activity were identified as fragment hits, rapidly diversified into 102 analogs in SuFEx reactions, and the sulfonamides were directly screened to yield drug-like inhibitors with 70-fold higher potency (IC50 = 94 nM). Moreover, the improved molecule J8-A34 can ameliorate cognitive function in Aß1-42-induced mouse model. Since this SuFEx linkage reaction succeeds on picomole scale for direct screening, this methodology can accelerate the development of robust biological probes and drug candidates.

Substituent effects on photosensitized splitting of thymine cyclobutane dimer by an attached indole.

In chromophore-containing cyclobutane pyrimidine dimer (CPD) model systems, solvent effects on the splitting efficiency may depend on the length of the linker, the molecular conformation, and the oxidation potential of the donor. To further explore the relationship between chromophore structure and splitting efficiency, we prepared a series of substituted indole-T< >T model compounds 2 a-2 g and measured their splitting quantum yields in various solvents. Two reverse solvent effects were observed: an increase in splitting efficiency in solvents of lower polarity for models 2 a-2 d with an electron-donating group (EDG), and vice versa for models 2 e-2 g with an electron-withdrawing group (EWG). According to the Hammett equation, the negative value of the slope of the Hammett plot indicates that the indole moiety during the T< >T-splitting reaction loses negative charge, and the larger negative value implies that the repair reaction is more sensitive to substituent effects in low-polarity solvents. The EDGs of the models 2 a-2 d can delocalize the charge-separated state, and low-polarity solvents make it more stable, which leads to higher splitting efficiency in low-polarity solvents. Conversely, the EWGs of models 2 e-2 g favor destabilization of the charge-separated state, and high-polarity solvents decrease the destabilization and hence lead to more efficient splitting in high-polarity solvents.

Synthesis, characterization, drug-loading capacity and safety of novel pH-independent amphiphilic amino acid copolymer micelles.

A novel block copolymer containing two polymeric components, poly(L-aspartic acid)-b-poly (L-phenylalanine) (PAA-PPA), was synthesized and its potential for the preparation of copolymer micelles with a poorly water-soluble drug was investigated in this study. The chemical structure and physical properties of PAA-PPA were characterized by FTIR, 1H NMR and TG. The degree of polymerization of PAA-PPA was calculated by analyzing the relative area of N-CH signal and C-CH3 of 1H NMR spectra. The critical micelle concentration (CMC) of the PAA-PPA achieved a minimum of 11.1 mg/L. Studies on the drug-free PAA-PPA solutions showed PAA-PPA aggregation into micellar type in the sub-150 nm size range. Furthermore, the size of the PAA-PPA micelles was found to be pH-independent between the pH range of 4.0 and 8.0, which could be favorable to avoid the limitation of the size change at the specified pH value seeking drug stability. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was studied as a poorly water-soluble model drug. The drug-loading and entrapment efficiency of the ATPR-loaded PAA-PPA micelles were 30.9 wt% and 87.9 %, respectively. The high drug-loading and entrapment efficiency were due to the synergistic effect of the micellar encapsulation and the binding interaction between drug and PAA-PPA. The ATPR-loaded PAA-PPA micelles showed a narrow size distribution, low zeta potential, high drug-loading capacity and good stable. The PAA-PPA was safer than Tween-80 and Cremophor EL (CrmEL) as an injectable pharmaceutical adjuvant for ATPR as indicated by the hemolysis and cytotoxicity studies. The novel amphiphilic amino acid copolymer can be considered as a prospective injectable delivery system for ATPR in terms of the pH-independent, greater drug-loading capacity and safety.

Discovery and Anti-Inflammatory Activity Evaluation of a Novel CDK8 Inhibitor through Upregulation of IL-10 for the Treatment of Inflammatory Bowel Disease In Vivo.

Increasing the anti-inflammatory cytokine interleukin-10 (IL-10) level is a promising strategy to suppress the progression of pathogenic inflammation including inflammatory bowel disease (IBD). Since cyclin-dependent kinase 8 (CDK8) inhibition can upregulate IL-10 abundance in activated myeloid-derived dendritic cells, it is considered to be an effective target for IBD treatment. Here, the complete discovery process of a novel CDK8 inhibitor as an anti-inflammatory agent was described. Starting with wogonin, structure-based optimization and structure-activity relationship (SAR) study were comprehensively carried out, and then lead compound 85 (N-(2-ethylphenyl)-5-(4-(piperazine-1-carbonyl)phenyl)nicotinamide) was developed as a potent druglike CDK8 inhibitor upregulating IL-10 both in vivo and in vitro. Also, compound 85 (with CDK8 IC50 = 56 nM, IL-10 enhancement rate 88%) exhibited effective anti-inflammatory activity in an animal model of IBD. These results confirmed that certain CDK8 inhibitor could be used as an effective anti-IBD drug.

Discovery of the Novel 1H-Pyrrolo[2,3-b]pyridine Derivative as a Potent Type II CDK8 Inhibitor against Colorectal Cancer.

Few targeted drugs were approved for treatment of colorectal cancer (CRC). Cyclin-dependent kinase 8 played a vital role in regulating transcription and was a key colorectal oncogene associated to colorectal cancer. Here, through de novo drug design and in depth structure-activity relationship analysis, title compound 22, (3-(3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)-N-(4-methyl-3-(trifluoromethyl)phenyl)propenamide), was discovered as a potent type II CDK8 inhibitor, which exhibited potent kinase activity with an IC50 value of 48.6 nM and could significantly inhibit tumor growth in xenografts of CRC in vivo. Further mechanism studies indicated that it could target CDK8 to indirectly inhibit ß-catenin activity, which caused downregulation of the WNT/ß-catenin signal and inducing cell cycle arrest in G2/M and S phases. More importantly, the title compound exhibited low toxicity with good bioavailability (F = 39.8%). These results could provide the reference for design of new type II CDK8 inhibitors against colorectal cancer.

Synthesis and biological evaluation of novel hybrids of phenylsulfonyl furoxan and phenstatin derivatives as potent anti-tumor agents.

Hybridization of nitric oxide (NO) donors with known anti-cancer agents have been emerged as a strategy to achieve improved therapeutic effect and to overcome chemo-resistance in cancer therapy. In this study, furoxan moiety as an efficient NO donor was introduced to phenstatin, a microtubule-interfering agent (MIA), leading to the design and synthesis of a series of furoxan-based NO-releasing arylphenones derivatives. In biological evaluation, the synthesized compounds showed moderate to potent anti-tumor activities against several human cancer cell lines. Among them, compound 15h showed the most potent activities against both chemo-sensitive and resistant cancer cell lines with IC50 values ranging from 0.008 to 0.021 µM. Further mechanistic studies revealed that 15h worked as a bifunctional agent exhibiting both tubulin polymerized inhibition and NO-releasing activities, resulting in potent anti-angiogenesis, colony formation inhibition, cell cycle arrest and apoptosis induction effects. In the nude mice xenograft model, 15h significantly inhibited the paclitaxel-resistant tumor growth with low toxicity, demonstrating the promising potential for further preclinical evaluation as a therapeutic agent, particularly for the treatment of chemo-resistant cancers.

Novel cannabidiol-carbamate hybrids as selective BuChE inhibitors: Docking-based fragment reassembly for the development of potential therapeutic agents against Alzheimer's disease.

Cannabidiol (CBD) and rivastigmine have been launched as drugs for treating dementia and cholinesterases (ChEs) are ideal drug targets. This study focused on developing novel ChE inhibitors as drug leads against dementia through molecular modeling and fragment reassembly approaches. A potent carbamate fragment binding to active site gorge of BuChE was found via a docking-based structural splicing approach, thus, 17 novel compounds were designed by structural reassembly. Compound C16 was identified as a highly selective potent BuChE inhibitor (IC50 = 5.3 nM, SI > 4000), superior to CBD (IC50 = 0.67 µM). C16 possessed BBB penetrating ability, benign safety, neuroprotection, antioxidant and pseudo-irreversible BuChE inhibition (Kd = 13 nM, k2 = 0.26 min-1), showing good drug-like properties. In vivo studies confirmed that C16 significantly ameliorated the scopolamine-induced cognition impairment, almost entirely recovered the Aß1-42 (icv)-impaired cognitive function to the normal level, showed better behavioral performance than donepezil and good anti-amyloidogenic effect. Hence, the potential BuChE inhibitor C16 can be developed as a promising disease-modifying treatment of AD.

Dual Response of Photonic Films with Chiral Nematic Cellulose Nanocrystals: Humidity and Formaldehyde.

Manipulating functional stimuli-responsive materials has been a hot topic in the research of smart sensors and anticounterfeiting encryption. Here, a novel functional chiral nematic cellulose nanocrystal (CNC) film showing dual responsiveness to humidity and formaldehyde gas was fabricated. The chiral nematic CNC iridescent film could respond to environmental humidity and formaldehyde gas changes by reversible motion. Interestingly, the humidity sensitivity of the CNC iridescent film could be gated by exposing the film to formaldehyde gas. At the same time, the formaldehyde-responsive behavior is strongly affected by the relative humidity (RH), and the response range could be tuned by changing the RH over a wide range. Importantly, the formaldehyde-induced color change could be altered from invisible to visible by the naked eye when the film was exposed to a humid environment. The mechanism of this dual response of the CNC iridescent film is ascribed to the synergistic effect of cooperation and competition between water and formaldehyde molecules by constructing physical cross-linking networks by hydrogen bonds among water, formaldehyde, and CNCs. Furthermore, the "RH-concentration of formaldehyde gas-color" ternary colorimetric system was simulated, which is thought to endow the CNC iridescent film with great potential to act as a sensor in the convenient visible detection of gaseous formaldehyde. Furthermore, this work provided a promising strategy to design multi-gas-sensitive devices with convenient detection, good stability, and excellent reversibility.

Effects of impregnation combined heat treatment on the pyrolysis behavior of poplar wood.

To investigate the effects of urea-formaldehyde (UF) resin impregnation combined heat treatment (IMPG-HT) on the pyrolysis behavior of poplar wood, the chemical composition, pyrolysis characteristics, pyrolysis kinetics, and gaseous products released during pyrolysis of untreated (control), IMPG-HT, IMPG and HT woods were analyzed. The results demonstrate that IMPG-HT changes pyrolysis behavior of poplar wood significantly. Unlike the control and HT samples, the thermogravimetric / derivative thermogravimetric (TG/DTG) curves of IMPG wood shift toward lower temperature, and the shoulder on DTG curves weaken or even disappear. The maximum mass loss rate of IMPG-HT samples decreases, and carbon residual yield increases to 23% or more and activation energy (E) increases sharply after conversion rate (α) reaching 0.80. HT improves the thermal stability of IMPG wood, which is represented by the increase of decomposition temperature (Td) and DTG peak temperature (Tpeak) and the higher E value of IMPG-HT wood. For the pyrolysis gaseous products, IMPG-HT wood produces nitrogen-containing gases (HNCO and NH3) due to the presence of UF resin, but the amounts of these gases are less than that produced by IMPG wood because the heat treatment had removed part of N elements.

Primary gastric squamous cell carcinoma presenting as a large submucosal mass: A case report and literature review.

RATIONALE: Primary gastric squamous cell carcinoma (SCC) is rarely encountered clinically. SCC, which presents as a submucosal tumor, is even rarer. Without the support of pathological evidence, it is difficult to make a correct preoperative diagnosis. Due to limited clinical data, the pathogenesis and treatment of gastric SCC remain unclear. PATIENT CONCERNS: A 69-year-old man was admitted to our hospital with unexplained weight loss. Endoscopy revealed a submucosal mass without any ulcer on its surface located on the body of the stomach. The results of 2 gastroscopic mucosal biopsies were chronic inflammation. DIAGNOSES: The clinical diagnosis by computed tomography (CT) and gastroscopy was gastrointestinal stromal tumor (GIST) preoperatively. The postoperative pathological examination demonstrated this tumor as moderately differentiated SCC. INTERVENTIONS: Total gastrectomy, distal pancreatectomy, and splenectomy were performed. OUTCOMES: The patient was discharged 7 days after the surgery without any complications. The follow-up CT scan showed no evidence of metastatic disease 6 months after surgery. LESSONS: Large primary gastric SCC could present as a submucosal mass. Gastroscopic mucosal biopsy may not be able to get tumor tissue due to inflammatory reaction.