Experimental Study on Vacuum Distillation Separation Characteristics of Tar Containing Solid Particles: Distributions of Light Components.

The impacts of the composition and properties of tar products on their utilization are of great importance, while the consequences of varying tar separation conditions on distillation fractions remain underexplored. Solid impurities in special tar products (e.g., subsurface in situ pyrolysis-derived tar-like substances) can contribute to the separation as well. In the present study, low-temperature coal tar (LTCT) was used as an analogue to pyrolysis product, mixed with semi-coke and coal dust, representing pyrolytic byproducts and nonpyrolytic substances, respectively. The LTCT mixtures were tested with vacuum distillation at various pressures and temperatures. The results revealed the role of pressure in fraction distribution across temperatures, with higher pressure concentrating fractions at lower temperatures. The impact of solid impurities on distillation primarily stemmed from adsorption. Minimal concentrations of solid impurities carried coal dust/semi-coke into the distillation, but higher levels retained them in the residue. The adsorption of coal dust was quite high at lower temperatures and waned as temperature increased, unlike semi-coke, which had consistent adsorption throughout the distillation. The present study can advance the understanding of vacuum distillation for tar products in the presence of solid impurities, offering a framework for the effective distillation/utilization of coal tar. By probing separation conditions, tar properties, and solid impurity effects, the present research will refine strategies for optimizing coal tar use, crucial for enhancing energy security and sustainable progress in China.

Evolution of H7N9 highly pathogenic avian influenza virus in the context of vaccination.

Human infections with the H7N9 influenza virus have been eliminated in China through vaccination of poultry; however, the H7N9 virus has not yet been eradicated from poultry. Carefully analysis of H7N9 viruses in poultry that have sub-optimal immunity may provide a unique opportunity to witness the evolution of highly pathogenic avian influenza virus in the context of vaccination. Between January 2020 and June 2023, we isolated 16 H7N9 viruses from samples we collected during surveillance and samples that were sent to us for disease diagnosis. Genetic analysis indicated that these viruses belonged to a single genotype previously detected in poultry. Antigenic analysis indicated that 12 of the 16 viruses were antigenically close to the H7-Re4 vaccine virus that has been used since January 2022, and the other four viruses showed reduced reactivity with the vaccine. Animal studies indicated that all 16 viruses were nonlethal in mice, and four of six viruses showed reduced virulence in chickens upon intranasally inoculation. Importantly, the H7N9 viruses detected in this study exclusively bound to the avian-type receptors, having lost the capacity to bind to human-type receptors. Our study shows that vaccination slows the evolution of H7N9 virus by preventing its reassortment with other viruses and eliminates a harmful characteristic of H7N9 virus, namely its ability to bind to human-type receptors.

Experimental Study on the Erosion-Corrosion Characteristics of Desulfurization Slurry on Stainless Steel Pipe Materials.

The recovery of low-grade waste heat from power plants greatly benefits energy conservation and emission reduction during electricity generation, while the waste heat utilization directly from desulfurization slurry is a significantly promising method to deeply recover such low-grade energy and has been developed in practical application. However, the pipe materials are subjected to erosion and corrosion challenges due to the high level of solid compositions and the presence of harmful ions, such as Cl-1, which requires further evaluation under the condition of slurry heat exchange. The present study aimed at an experimental study on the erosion-corrosion characteristics of desulfurization slurry on three types of stainless steel, including type 304, 316L, and 2205. Both mass loss and micromorphology features were analyzed with possible mechanisms elucidated. The erosion-corrosion rate is weak at low temperatures, while the increase in the slurry temperature clearly promotes its rate. The influence of the temperature on the corrosion resistance of 304 is much greater than that of 2205. With an increase in duration time, the weight loss rate of stainless steel in the desulfurization slurry declines, and the changing trend of metal mass slightly slows down. The present study offers a better understanding of the erosion-corrosion behaviors of three types of stainless steel under flow and heat transfer conditions of a desulfurization slurry.

Effects of tumour budding on adjuvant chemotherapy in colorectal cancer.

BACKGROUND: High tumour budding has been indicated as a risk factor of poor survival in colorectal cancer. This study aimed to investigate the impact of tumour budding grades and the use of adjuvant chemotherapy on prognosis in patients with colorectal cancer. METHODS: This study included consecutive colorectal cancer patients who underwent radical surgery for primary colorectal adenocarcinoma at The Sixth Hospital of Sun Yat-sen University between 2009 and 2019. Tumour budding was assessed based on the recommendations of the International Tumor Budding Consensus Conference using haematoxylin and eosin (H&E)-stained slides with tumour samples. The primary outcome of interest was to correlate tumour budding with disease-free survival and overall survival; the secondary outcome was investigation of the impact of adjuvant therapy on different tumour budding grades. In addition, a subgroup analysis was performed for the effects of lymphocytic infiltration on adjuvant chemotherapy in patients with Bd3. RESULTS: Of 709 eligible patients, 412 with colorectal cancer were included. According to the International Tumor Budding Consensus Conference, 210 (50.9 per cent), 127 (30.8 per cent) and 75 (18.2 per cent) were classified as low budding (Bd1), intermediate budding (Bd2) and high budding (Bd3) respectively. Patients with Bd1, Bd2 and Bd3 had 5-year disease-free survival rates of 82.9 per cent, 70.1 per cent and 49.3 per cent respectively, and 5-year overall survival rates of 90 per cent, 79.5 per cent and 62.7 per cent respectively (P <0.001). Adjuvant chemotherapy yielded a significant survival benefit in patients with Bd3 (5-year disease-free survival, 65 per cent versus 31.4 per cent, P <0.001; 5-year overall survival, 84.4 per cent versus 63.1 per cent, P <0.001), but not in those with Bd1 or Bd2. In patients with Bd3, the benefit of adjuvant chemotherapy was maintained in those with low, but not high lymphocytic infiltration. CONCLUSION: High grade of tumour budding was strongly correlated with poorer survival outcomes in colorectal cancer. Patients with Bd3 benefited from adjuvant chemotherapy, with the exclusion of patients with high lymphocytic infiltration.

Long-term oncological outcomes of transanal versus laparoscopic total mesorectal excision for mid-low rectal cancer: a retrospective analysis of 2502 patients.

BACKGROUND: Transanal total mesorectal resection (taTME) has recently emerged as a promising surgical approach for the treatment of mid-low rectal cancer. However, there is limited evidence on the long-term survival outcomes associated with taTME. This retrospective study aimed to compare the overall survival (OS), disease-free survival (DFS), and cancer-specific survival of taTME and laparoscopic TME (laTME) in patients with mid-low rectal cancer. MATERIALS AND METHODS: From July 2014 to June 2022, a total of 3627 patients were identified from two prospective cohorts: the laparoscopic rectal surgery cohort and the CNTAES cohort. To balance the baseline characteristics between the taTME and laTME groups, propensity score matching (PSM) was performed. RESULTS: A total of 2502 patients were included in the study. Prior to PSM, the laTME group comprised 1853 patients, while the taTME group comprised 649 patients. The 5-year OS (82.9% vs. 80.4%, P =0.202) and 5-year DFS (74.4% vs. 72.5%, P =0.167) were comparable between the taTME and laTME groups. After PSM, the taTME group showed no statistically significant difference in the 5-year OS (83.1% vs. 79.2%, P =0.101) and 5-year DFS (74.8% vs. 72.1%, P =0.135) compared to the laTME group. Subgroup analysis further suggested that taTME may potentially reduce the risk of death [hazard ratio 0.652; (95% CI, 0.452-0.939)] and disease recurrence [hazard ratio 0.736; (95% CI, 0.562-0.965)] specifically in patients with low rectal cancer. CONCLUSION: In this study, taTME demonstrated comparable oncologic safety to laTME in patients with mid-low rectal cancer. Moreover, the results indicate that taTME may confer potential survival benefits for patients with low rectal cancer.

High expression of DNMT3A and DNMT3B regulatory factors of TGFB in non-neoplastic liver tissues of HCC.

Increased expression of TGFB regulatory factors DNMT3A and DNMT3B in non-neoplastic liver tissues of HCC patients is the goal of this study. Furthermore, we demonstrate that TGF- is capable of elevating the percentage of CD133+ cells present in liver cancer cell lines in a manner that is both consistent and long-lasting over several cell divisions. This process is linked to stable alterations in DNA methylation that occur over the whole of the genome and continue even after cell division. In addition, the silencing of de novo DNA methyl-transferases with siRNA is able to inhibit the phenotypic changes that are induced by TGF-. According to the findings of our research, there is a self-sustaining interaction between the DNA methylation machinery and the TGF- signaling pathway, which may be significant in the development of cellular phenotypes. CD133 positive and negative fractions expand within liver cancer cell lines in proportions that remain stable throughout time. In contrast to their CD133- counterparts, MACS-sorted CD133+ Huh7cells demonstrated the ability to shape themselves into spheres when grown under non-attachment circumstances. This study also found that the TGF- is responsible for the de novo induction of CD133, which is linked to an increase in the expression of DNMT3 genes and there is a correlation between the TGF-induced transition in the cell subpopulation and a distinct DNA methylome. TGF- has the potential to generate genome-wide alterations in DNA methylation, which ultimately leads to a persistent shift in the fraction of liver cancer cell subpopulations.

The Deepest Extent of Acellular Mucin Pools in Resected Locally Advanced Rectal Cancer With Pathological Complete Response After Preoperative Chemoradiotherapy: A Hidden Killer?

For patients with locally advanced rectal cancer (LARC) with pathological complete response (pCR), the clinical significance of the distribution extent of acellular mucin pools (AMP) distribution remains unclear, so this study was conducted to address key unanswered questions. We performed a retrospective analysis of 317 patients with LARC with pCR after preoperative chemoradiotherapy and total mesorectal resection from January 2011 to June 2020. Based on AMP existence and the deepest tissue layer of distribution, patients were assigned new stages. The patient information was recorded, and the main outcome measures included 5-year disease-free survival (DFS) and 5-year overall survival (OS). A total of 83/317 (26.2%) patients exhibited AMP, and disease recurrence occurred in 46/317 (14.5%) patients. Over the 5-year median follow-up period, the patients with AMP showed 5-year DFS rates (75.9% vs. 88.9%, P =0.004) and 5-year OS rates (85.5% vs. 95.7%, P =0.002) statistically lower than those of patients without AMP. Disease recurrence was seen in 15/54 (27.8%) patients with AMP within the subserosa and/or the serosa, or adipose tissue. Univariate and multivariate analysis showed that the existence of AMP within the subserosa and/or the serosa, or adipose tissue was an independent risk factor for DFS [hazard ratio (HR): 2.344; 95% confidence interval (CI): 1.256-4.376; P =0.007] and OS [HR: 3.374; 95% CI: 1.438-7.917; P =0.005]. The new stages based on the deepest extent of AMP were related to worse DFS ( P =0.004) and OS ( P =0.003) rates among patients with pCR. In conclusion, the presence of AMP might reduce the prognosis of LARC patients with pCR after chemoradiotherapy, especially in patients with AMP in deeper tissue layers. Therefore, the influence of the deepest AMP extent might be worth considering in staging. Moreover, the revised staging of patients with pCR according to the deepest extent of AMP, which is unrelated to the clinical T stage, might facilitate postoperative management.

Clinical significance of neoadjuvant chemotherapy for locally advanced colorectal cancer patients with deficient mismatch repair: possibly residual value in the era of immunotherapy.

Background: Deficient mismatch repair (dMMR) or microsatellite instability is one of the well-established molecular biomarkers in colorectal cancer (CRC). The efficiency of neoadjuvant chemotherapy (NAC) in locally advanced colorectal cancer (LACC) patients with dMMR is unclear. Objectives: We assessed the tumor response and clinical outcome in LACC patients with dMMR received NAC. Design: Retrospective, single-center analysis. Methods: From 2013 to 2018, a total of 577 LACC patients with dMMR who underwent radical surgery were identified. Among them, 109 patients who received adjuvant chemotherapy were further screened out for analysis. According to whether receiving NAC or not, 109 patients were divided into two groups with the purpose of retrospectively analyzing their characteristics, treatment, and survival results, especially the 5-year disease-free survival (DFS) and 5-year overall survival. Results: Baseline characteristics were matched between the two groups. One of 40 patients in NAC group recurred, while 13 of 69 patients in non-NAC group recurred. Univariate and multivariate analyses showed that NAC (hazard ratio: 0.115; 95% confidence interval: 0.015-0.897; p = 0.039) was independent influence factor for DFS. In NAC group, there were 13/40 (32.5%) patients for tumor regression grade 1 and 27/40 (67.5%) patients converted clinical positive N-stage into negative N-stage. Conclusion: In this study, NAC was associated with better tumor downstaging and longer 5-year DFS in LACC patients with dMMR. Consequently, NAC might be an additional treatment choice when it comes to such patients in the future.

Clinical significance of adjuvant chemotherapy for pathological complete response rectal cancer patients with acellular mucin pools after neoadjuvant chemoradiotherapy.

Background: Approximately 15-30% of locally advanced rectal cancer (LARC) patients achieved pathological complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision, but the clinical significance of adjuvant chemotherapy (ACT) for pCR patients remains unclear. Objectives: To determine whether LARC pCR patients can benefit from the administration of ACT. Design: Single center retrospective study. Methods: This study retrospectively included 280 LARC patients who achieved pCR after CRT and surgery from 2011 to 2019. The information of patients was recorded. Main outcome measures included 5-year disease-free survival (DFS) and 5-year overall survival. Subgroup analysis was conducted on whether pCR patients with acellular mucin pools received ACT or not. Results: A total of 74/280 (26.4%) patients were identified with acellular mucin pools. Disease recurrence occurred in 38/280 (13.6%) patients, and in the subgroup of patients with acellular mucin pools, 15/74 (20.3%) patients developed distant metastases. The existence of acellular mucin pools was associated with worse DFS (79.7% versus 88.8%, P = 0.037). Among pCR patients with acellular mucin pools, 9/25 (36.0%) of non-ACT patients occurred recurrence, and ACT was beneficial for improving DFS (hazard ratio: 0.245; 95% confidence interval: 0.084-0.719; P = 0.010). Conclusions: The existence of acellular mucin pools may represent a sign of invasive tumor biology, which indicated a negative prognosis. ACT can improve the prognosis of patient with acellular mucin pools, so ACT should be considered for them.

Genetic analysis and biological characterization of H10N3 influenza A viruses isolated in China from 2014 to 2021.

The H10 subtypes of avian influenza viruses pose a continual threat to the poultry industry and human health. The sporadic spillover of H10 subtypes viruses from poultry to humans is represented by the H10N8 human cases in 2013 and the recent H10N3 human infection in 2021. However, the genesis and characteristics of the recent reassortment H10N3 viruses have not been systemically investigated. In this study, we characterized 20 H10N3 viruses isolated in live poultry markets during routine nationwide surveillance in China from 2014 to 2021. The viruses in the recent reassortant genotype acquired their hemagglutinin (HA) and neuraminidase (NA) genes from the duck H10 viruses and H7N3 viruses, respectively, whereas the internal genes were derived from chicken H9N2 viruses as early as 2019. Receptor-binding analysis indicated that two of the tested H10N3 viruses had a higher affinity for human-type receptors than for avian-type receptors, highlighting the potential risk of avian-to-human transmission. Animal studies showed that only viruses belonging to the recent reassortant genotype were pathogenic in mice; two tested viruses transmitted via direct contact and one virus transmitted by respiratory droplets in guinea pigs, though with limited efficiency. These findings emphasize the need for enhanced surveillance of H10N3 viruses.

Antioxidant and antimicrobial characteristics of ethyl acetate polar fractions from walnut green husk.

Walnut green husk (WGH) is rich in natural compounds and is valued as a potential source of antioxidant and antimicrobial properties. In this study, the antioxidant and antimicrobial activities of petroleum ether polar fraction, dichloromethane polar fraction, ethyl acetate polar fraction (EAPF), and n-butanol polar fraction from WGH were analyzed. The results showed that EAPF exhibited the highest total flavonoid content (65.74 ± 1.01 mg rutin equivalents [RE]/g dry weight [DW]) and total phenol content (48.73 ± 1.09 mg gallic acid equivalent [GAE]/g DW), with the highest 2,2-diphenyl-1-picrylhydrazyl, hydroxyl radical (•OH), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonate scavenging activity compared with other fractions. EAPF also showed good antibacterial activity against Escherichia coli and Bacillus cereus vegetative cells, with a diameter of inhibition zones of 33.5 and 37.6 mm, respectively, a minimum inhibitory concentration of 31.25 mg/ml and a minimum bactericidal concentration of 62.5 mg/ml, which inhibited the growth of both bacteria. Analysis of the antibacterial mechanism demonstrated that EAPF damaged the integrity of the cell membrane, increased the membrane permeability, and triggered the leakage of intracellular material. In addition, ultrahigh performance liquid chromatography-tandem with mass spectrometry analysis revealed that 8 polyphenols and 14 flavonoids were mainly present in EAPF, such as chlorogenic acid (C16 H18 O9 ), gallic acid (C7 H6 O5 ), vanillic acid (C8 H8 O4 ), ferulic acid (C10 H10 O4 ), epicatechin (C15 H14 O6 ), catechin (C15 H14 O6 ), hesperetin (C16 H14 O6 ), naringenin (C15 H12 O5 ), hyperin (C21 H20 O12 ), luteolin (C15 H10 O6 ), and so on. Therefore, WGH had the potential to be developed as a natural antioxidant and antibacterial material. PRACTICAL APPLICATION: Our work indicates that WGH contains abundant flavonoids and polyphenols compounds. Therefore, the plant byproducts like WGH may have a promising application as a source of antimicrobial and antioxidant additives.

Structure-activity relationships and the underlying mechanism of α-amylase inhibition by hyperoside and quercetin: Multi-spectroscopy and molecular docking analyses.

Inhibiting the activity of α-amylase has been considered an effective strategy to manage hyperglycemia. Hyperoside and quercetin are the main natural flavonoids in various plants, and the inhibition mechanism on α-amylase remains unclear. In this study, the structure-activity relationships between hyperoside/quercetin and α-amylase were evaluated by enzyme kinetic analysis, multi-spectroscopic techniques, and molecular docking analysis. Results showed that hyperoside and quercetin exhibited significant α-amylase inhibitory activities with IC50 values of 0.491 and 0.325 mg/mL, respectively. The α-amylase activity decreased in the presence of hyperoside and quercetin in a competitive and noncompetitive manner, respectively. UV-vis spectra suggested that the aromatic amino acid residues (Trp and Tyr) microenvironment of α-amylase changed in the presence of these two flavonoids. FTIR and CD spectra showed the vibrations of the amide bands and the secondary structure content changes. The fluorescence quenching mechanism of α-amylase by hyperoside and quercetin belonged to the static quenching type. Finally, molecular docking intuitively showed that hyperoside/quercetin formed hydrogen bonds with the key active site residues (Asp197, Glu233, and Asp300) in α-amylase. MD simulation indicated hyperoside/quercetin-α-amylase docked complexes had good stability. Taken together, this research provides new sights to developing potent drugs or functional foods with hyperoside and quercetin, offering new avenues for hyperglycemia treatment.

Potential Application of Luteolin as an Active Antibacterial Composition in the Development of Hand Sanitizer Products.

Antibacterial hand sanitizers could play a prominent role in slowing down the spread and infection of hand bacterial pathogens; luteolin (LUT) is potentially useful as an antibacterial component. Therefore, this study elucidated the antibacterial mechanism of LUT against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) and developed an antibacterial hand sanitizer. The results showed that LUT had excellent antibacterial activity against both E. coli (minimum inhibitory concentration (MIC) = 312.5 µg/mL, minimal bactericidal concentration (MBC) = 625 µg/mL), and S. aureus (MIC = 312.5 µg/mL, MBC = 625 µg/mL). Furthermore, LUT induced cell dysfunction in E. coli and S. aureus, changed membrane permeability, and promoted the leakage of cellular contents. Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) analysis showed that LUT treatment affected cell structure and disrupted cell membrane integrity. The Fourier transform infrared analysis (FTIR) also confirmed that the LUT acted on the cell membranes of both E. coli and S. aureus. Overall, the application of LUT in hand sanitizer had better inhibition effects. Therefore, this study could provide insight into expanding the application of LUT in the hand sanitizer markets.

Juglone Inhibits Listeria monocytogenes ATCC 19115 by Targeting Cell Membrane and Protein.

Foodborne disease caused by Listeria monocytogenes is a major global food safety problem. A potential solution is the antimicrobial development of the highly bioactive natural product juglone, yet few studies exist on its antibacterial mechanism against L. monocytogenes. Thus, we aimed to elucidate the antibacterial mechanism of action of juglone against L. monocytogenes by determining the resultant cell morphology, membrane permeability, membrane integrity, and proteome changes. The minimum inhibitory concentration of juglone against L. monocytogenes was 50 µg/mL, and L. monocytogenes treated with juglone had longer lag phases compared to controls. Juglone induced L. monocytogenes cell dysfunction, leakage of potassium ions, and membrane potential hyperpolarization. Confocal laser scanning microscopy and field-emission-gun scanning electron microscope assays revealed clear membrane damage due to juglone treatment. Fourier transform infrared analyses showed that L. monocytogenes responded to juglone by some conformational and compositional changes in the molecular makeup of the cell membrane. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that juglone either destroyed proteins or inhibited proteins synthesis in L. monocytogenes. Therefore, our findings established juglone as a natural antibacterial agent with potential to control foodborne L. monocytogenes infections.

Chronic disease management practices and factors associated with health-related quality-of-life for persons with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy.

BACKGROUND: The main objective of this study was to explore health-related quality of life (HRQoL) profiles, chronic disease management practices and key factors associated with HRQoL in 540 patients with chronic myeloid leukemia in chronic phase (CML-CP) administered tyrosine kinase inhibitors (TKIs). METHODS: Adult CML-CP patients treated with TKIs in Henan Cancer Hospital from March 2015 to October 2019 were assessed via questionnaires, including demographic characteristics, TKI medications, participation in CML disease management, and HRQoL, in a cross-sectional investigation. Respondents were anonymous. Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) was used to measure HRQoL. A multivariate linear regression model with stepwise entry was used to investigate variables independently associated with HRQoL domain and total scores. RESULTS: Totally, 540 respondents were included; 302 (55.93%) were male. Mean participant age was 42.90±13.00 years; 169 (31.3%), 178 (32.9%) and 193 (35.7%) individuals had a low, moderate or high disease management level, respectively. Except for insignificant event-free survival information, participants with higher disease management levels also had significantly higher rates of completing re-examination, drug withdrawal, cytogenetic response (CcyR) and/or major molecular response (MMR) (all P<0.01). Moreover, higher disease management level was accompanied by eight significantly higher HRQoL domains (all P<0.01). In multivariate linear regression analysis, variables significantly associated with a higher HRQoL included: (I) high disease management level (B=3.68, P=0.046); (II) transportation convenience (B=6.67, P<0.001); (III) family annual income >10,000 CNY (B=5.97, P<0.001); (IV) completed re-examination (B=4.58, P=0.036); (V) MMR (B=3.75, P=0.021) and CcyR (B=5.15, P=0.035). Female sex (B=-3.53, P=0.010), single status or divorce (B=-1.89 and -2.94, P=0.005 and 0.011), and low education level (B=-1.44, P=0.019) were significantly associated with lower HRQoL. CONCLUSIONS: Higher disease management level was significantly associated with higher elevated treatment efficacy and HRQoL in Chinese individuals with CML-CP administered TKIs. These data indicate the importance of chronic disease management on people's HRQoL and clinical outcome.

Transanal versus Laparoscopic Total Mesorectal Excision in Male Patients with Low Tumor Location after Neoadjuvant Therapy: A Propensity Score-Matched Cohort Study.

Background: Since Sylla and Lacy successfully reported the transanal total mesorectal excision in 2010, taTME was considered to have the potential to overcome some problematic laparoscopic cases in male, low advanced rectal cancer. However, the evidence is still lacking. This study compared the short and long outcomes of taTME with laTME in these "challenging" patients to explore the advantages of taTME among the patients. Method: After propensity score matching analysis, 106 patients were included in each group from 325 patients who met the including standard. Statistical analysis was used to compare the differences of perioperative outcomes, histopathological results, and survival results between taTME and laTME groups. Results: The mean time of pelvic operation in the taTME group was significantly shorter than in the laTME group (62.2 ± 14.2 mins vs 81.1 ± 18.9 mins, P = 0.003). The complication incidence rate and the rate of protective loop ileostomy in the taTME group were significantly lower than those in the laTME group (19.8% vs 38.7%, P = 0.003 and 70.8% vs 92.5%, P < 0.001). In long-term result, there was no significant difference between the two groups for 3-year OS (87.3% vs 85.4%, P = 0.86) or 3-year DFS (74.9% vs 70.1%, P = 0.92). The 2-year cumulative local recurrence rate was similar between the two groups (1.1% vs 5.8%, P = 0.22). Conclusion: This study demonstrated that taTME might reduce the incidence of postoperative complications, especially of anastomotic leakage in these "challenging" patients. taTME may be considered to have clear advantages for "challenging" patients.

Electron beam irradiation enhanced extraction and antioxidant activity of active compounds in green walnut husk.

Green walnut husk (GWH) contains abundant active compounds and is valued as a potential source of natural antioxidants. This study aimed at assessing the impact of electron beam irradiation (EBI) pretreatment on the extraction yield and antioxidant activity of active compounds in GWH. The ultrasonic extraction of active substances was optimized by response surface method (RSM). Scanning electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction revealed physical structure changes in GWH powder. After EBI pretreatment, the content of polyphenols, flavonoids, and triterpenes in GWH increased by 18.88%, 43.00%, and 11.08%, respectively. Irradiation doses up to 30 kGy, DPPH, OH, and ABTS radical scavenging activity and reducing power of the crude extract were enhanced by 9.56%, 15.62%, 15.60%, and 36.98%, respectively. This was significantly different (P < 0.05) than the non-irradiated GWH. Therefore, EBI is a new pretreatment technology with potential application in the extraction and utilization of GWH.

Will the clinical development of 4th-generation "double mutant active" ALK TKIs (TPX-0131 and NVL-655) change the future treatment paradigm of ALK+ NSCLC?

Our current treatment paradigm of advanced anaplastic lymphoma kinase fusion (ALK+) non-small cell lung cancer (NSCLC) classifies the six currently approved ALK tyrosine kinase inhibitors (TKIs) into three generations. The 2nd-generation (2G) and 3rd-generation (3G) ALK TKIs are all "single mutant active" with varying potencies across a wide spectrum of acquired single ALK resistance mutations. There is a vigorous debate among clinicians which is the best upfront ALK TKI is for the first-line (1L) treatment of ALK+ NSCLC and the subsequent sequencing strategies whether it should be based on the presence of specific on-target ALK resistance mutations or not. Regardless, sequential use of "single mutant active" ALK TKIs will eventually lead to double ALK resistance mutations in cis. This has led to the creation of fourth generation (4G) "double mutant active" ALK TKIs such as TPX-0131 and NVL-655. We discuss the critical properties 4G ALK TKIs must possess to be clinically successful. We proposed conceptual first-line, second-line, and molecularly-based third-line registrational randomized clinical trials designed for these 4G ALK TKIs. How these 4G ALK TKIs would be used in the future will depend on which line of treatment the clinical trial design(s) is adopted provided the trial is positive. If approved, 4G ALK TKIs may usher in a new treatment paradigm for advanced ALK+ NSCLC that is based on classifying ALK TKIs based on the intrinsic functional capabilities ("singe mutant active" versus "double mutant active") rather than the loosely-defined "generational" (first-, second-,third-,fourth-) classification and avoid the current clinical approaches of seemingly random sequential use of 2G and 3G ALK TKIs.