Using ligand regulation, metal replacement, and ligand doping strategies on Zr-FUM to improve methane separation from coalbed gas.

Developing adsorbents suitable for industrial applications that can effectively enhance the separation of methane (CH4) from nitrogen (N2) in coalbed gas is crucial to improve energy recovery and mitigate greenhouse gas emissions. In this study, three modification strategies were implemented on Zr-FUM, including ligand regulation, metal replacement, and ligand doping, to synthesize Zr-FDCA, Al-FUM, and Zr-FUM-FA, with the aim of improving the performance of CH4/N2 separation under humid conditions. The results demonstrated that the promotion of robust orbital overlap and strengthened electrovalent bonding on adsorbents can selectively enhance CH4 adsorption. As a result, Zr-FUM-FA achieved a saturated CH4 adsorption capacity of 1.37 mmol/g, a CH4 working window of 307 s, and a CH4/N2 sorbent selection parameter (Ssp) of 47.31, exceeding the performance of most reported adsorbents. Analyses of the pore structure, surface morphology, and functional groups revealed that the presence of an ultramicropore proximity to CH4, reduced static resistance, and enhanced electrovalent bond were key factors for CH4 separation. Grand Canonical Monte Carlo and Density Functional Theory studies indicated that the introduction of -C-H- in FA played a crucial role in enhancing CH4 adsorption. Optimization of adsorption parameters using the Aspen adsorption package showed that in a dual-adsorbent bed system, the recovery and purity of CH4 in Zr-FUM-FA reach 99.5% and 97.3%, respectively, providing important theoretical support for the improvement of CH4 recovery in the pressure swing adsorption process from coalbed gas.

Treatment-related adverse events of immune checkpoint inhibitors combined with angiogenesis inhibitors in advanced lung cancer: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) with angiogenesis inhibitors have been used to treat advanced lung cancer. Their associated treatment-related adverse events (trAEs) are currently considered acceptable; however, no conclusion has been reached. We aimed to summarize the trAEs caused by ICIs combined with angiogenesis inhibitors in patients with advanced lung cancer. METHODS: Pulled studies met the following criteria: patients with advanced lung cancer who received treatment involving ICIs combined with angiogenesis inhibitors (with or without chemotherapy) in interventional or observational studies. Results included the type and number of trAEs or immune-related adverse events (irAEs), treatment-associated discontinuation and mortality, overall survival (OS), and progression-free survival (PFS). PROSPERO: CRD42022337656. RESULTS: The study enrolled 32 trials involving 2313 patients who had 7768 any-grade trAEs and 1078 grade ≥3 trAEs. The pooled incidences were 87.33% (95% confidence interval [CI]: 79.49-93.65; I2 = 94.04%) for any-grade trAEs, and 38.63% (95% CI: 28.28-49.50; I2 = 95.61%) for grade ≥3 trAEs. There were 132 kinds of any-grade trAEs involving 18 systems, and 99 kinds of grade ≥3 trAEs involving 16 systems. For all trAEs, we observed significant differences in the line of therapy, trial design, therapy combination, and types of angiogenesis inhibitors (all P < 0.05). The rate of trAEs increased with dosage and frequency of medication. Pooled incidences of discontinuation and mortality were 10.64% and 0.81%, respectively. Nearly 647 patients experienced irAEs, including 636 any-grade irAEs and 154 grade ≥3 irAEs. CONCLUSIONS: Overall, the incidence of trAEs caused by ICIs combined with angiogenesis inhibitors is generally acceptable. These trAEs have a wide spectrum nearly covering the full range of adverse events. Grade ≥3 trAEs are more closely associated with angiogenesis inhibitors than any grade. However, treatment-associated mortality remains concerning.

Traditional Chinese medicine in the era of immune checkpoint inhibitor: theory, development, and future directions.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management and have been widely applied; however, they still have some limitations in terms of efficacy and toxicity. There are multiple treatment regimens in Traditional Chinese Medicine (TCM) that play active roles in combination with Western medicine in the field of oncology treatment. TCM with ICIs works by regulating the tumor microenvironment and modulating gut microbiota. Through multiple targets and multiple means, TCM enhances the efficacy of ICIs, reverses resistance, and effectively prevents and treats ICI-related adverse events based on basic and clinical studies. However, there have been few conclusions on this topic. This review summarizes the development of TCM in cancer treatment, the mechanisms underlying the combination of TCM and ICIs, existing studies, ongoing trials, and prospects for future development.

Influence of ligands within Al-based metal-organic frameworks for selective separation of methane from unconventional natural gas.

Efficient CH4/N2 separation from unconventional natural gas is vital for both energy recycling and climate change control. Figuring out the reason for the disparity between ligands in the framework and CH4 is the crucial problem for developing adsorbents in PSA progress. In this study, a series of eco-friendly Al-based MOFs, including Al-CDC, Al-BDC, CAU-10, and MIL-160, were synthesized to investigate the influence of ligands on CH4 separation through experimental and theoretical analyses. The hydrothermal stability and water affinity of synthetic MOFs were explored through experimental characterization. The active adsorption sites and adsorption mechanisms were investigated via quantum calculation. The results manifested that the interactions between CH4 and MOFs materials were affected by the synergetic effects of pore structure and ligand polarities, and the disparities of ligands within MOFs determined the separation efficiency of CH4. Especially, the CH4 separation performance of Al-CDC with high sorbent selection (68.56), moderate isosteric adsorption heat for CH4 (26.3 kJ/mol), and low water affinity (0.1 g/g at 40% RH) was superior to most porous adsorbents, which was attributed to its nanosheet structure, proper polarity, reduced local steric hindrance, and extra functional groups. The analysis of active adsorption sites indicated that hydrophilic carboxyl groups and hydrophobic aromatic ring were the dominant CH4 adsorption sites for liner ligands and bent ligands, respectively. The methylene groups with saturated C-H bonds enhanced the wdV interaction between ligands and CH4, resulting in the highest binding energy of CH4 for Al-CDC. The results provided valuable guidance for the design and optimization of high-performance adsorbents for CH4 separation from unconventional natural gas.

Efficacy and Safety of Immune Checkpoint Inhibitors in Patients with Cancer and Hepatitis B or C: A Systematic Review and Meta-Analysis.

Background: Immune checkpoint inhibitors (ICIs) have changed the situation of tumor therapy in recent years. However, for security reasons, those special populations are often excluded from clinical trials, such as infected hepatitis B or hepatitis C patients. ICIs are systematically reviewed and meta-analyzed for the first time in patients infected with hepatitis B or C in this paper. Methods: The relevant studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science until October 2022. Trials and observational studies meeting the inclusion criteria were included. The outcomes included the effectiveness of ICIs in patients with HBC/HCV (ORR, DCR, mOS, and mPFS), the incidence of adverse reactions, high-grade adverse reactions, and abnormal liver enzymes. At the same time, these indexes were compared with those of uninfected patients. Results: A total of 2,625 patients were enrolled, involving 1,179 patients with hepatitis (HBV or HCV). We found that ICIs showed higher ORR (25.80% vs. 18.10%) and DCR (66.22% vs. 58.74%) in patients with hepatitis B/C than those without infection. In terms of survival time, patients with hepatitis virus infection showed longer mOS (15.44 m vs. 13.30 m) but shorter mPFS (4.94 m vs. 5.01 m) than uninfected patients. As for safety data, patients with hepatitis showed a lower incidence of all-grade irAEs (68.02% vs. 70.43%) than uninfected patients, while that of 3-4 irAEs (21.27% vs. 21.79%) was similar in the two groups. However, hepatic dysfunction was more common and serious in hepatitis patients. Four HBVr and no HCVr were observed. Conclusion: According to this meta-analysis, ICIs are effective and safe for patients with hepatitis B or C, but basic liver enzymes have to be evaluated before treatment to avoid liver adverse events.

Long-term survival in extensive-stage small-cell lung cancer treated with different immune checkpoint inhibitors in multiple-line therapies: A case report and literature review.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, is highly prone to recurrence, and has a short survival period. It is very difficult to achieve long-term survival in ES-SCLC, which has not been significantly improved in the last 20 years. For a long time, platinum-based chemotherapy has occupied the core position in the treatment of small-cell lung cancer (SCLC), but there are few options for treatment drugs or regimens, and if disease progression occurs, the options for follow-up regimens are obviously limited. The advent of immunotherapy has changed this situation to some extent, and immunotherapy has shown some effects in improving efficiency and prolonging survival, whether in first- or third-line therapy, but it is still unsatisfactory. Case presentation: A 57-year-old patient with ES-SCLC experienced disease progression after four lines of treatment including synchronous radiotherapy, chemotherapy, and antiangiogenesis. However, the patient still benefited when switching to the programmed cell death receptor-1 (PD-1) inhibitor toripalimab in combination with chemotherapy in the fifth line. Even after the development of immune resistance, the patient still benefited after switching to tislelizumab in combination with different chemotherapy regimens or alone in the sixth and seventh lines. Following the progression of tislelizumab in combination with chemotherapy, the patient again profited after switching to durvalumab in combination with anlotinib and again achieved a progressive-free survival (PFS) of 11 months. Overall, the patient achieved a total of 45 months of PFS and 50 months of overall survival (OS), with a shocking and exciting 30 months of PFS achieved in the immune combination phase alone. Conclusion: We report a patient with ES-SCLC who achieved long-term survival after at least eight lines of therapy including chemotherapy, antiangiogenesis, and different immune checkpoint inhibitors (ICIs). This suggests that long-term survival in SCLC is possible with aggressive, combined, and standardized treatment. Otherwise, immunotherapy postline enablement can still benefit patients, rechallenge after immune resistance is also possible in SCLC, and combination with chemotherapy or antiangiogenic therapy can improve the efficacy and prolong the survival. This will provide new ideas and options for the selection of treatment options for SCLC.

Changes of IL-6 And IFN-γ before and after the adverse events related to immune checkpoint inhibitors: A retrospective study.

Immune checkpoint inhibitors (ICIs) have changed the status of tumor immunotherapy. ICIs-related adverse events (irAEs) have the high incidence and are difficult to predict and prevent. Researches have suggested that changes of cytokines were associated with irAEs. This study focused on the changes of interleukin-6 (IL-6) and interferon-γ in patients before and after irAEs and trying to find the biomarkers of irAEs. Collect basic data of patients who were treated with ICIs in China-Japan Friendship Hospital from January 2017 to August 2021 and had irAEs. Make statistics on IL-6 and INF-γ in the blood before and after irAEs. A total of 10 patients were enrolled, including 7 males and 3 females. According to statistical analysis, the IL-6 concentration level after irAEs was significantly higher than before, and the difference was statistically significant (P = .023); the interferon-γ concentration level was not changed significantly from before, the difference was not statistically significant (P = .853). The elevation of IL-6 was associated with the occurrence of adverse reactions in ICIs.

Radiation induced lung injury (RILI) after postoperative intensity modulated proton therapy (IMPT) in a patient with stage III locally advanced lung adenocarcinoma: a case report.

Background: Postoperative radiation therapy (PORT) remains the critical therapy for stage III non-small cell lung cancer (NSCLC). Radiation induced lung injury (RILI) is common and affects the clinical outcome. Proton therapy (PT) is a new-style radiotherapy with accurate distribution of curative dose to tumor and increased organ-at-risk (OAR) sparing, which potentially decrease the incidence of RILI. Intensity modulated proton therapy (IMPT) is more flexible and conformal one. Case Description: In the case, we report a 47-year-old man with stage III locally advanced lung adenocarcinoma developing RILI after IMPT. The man had no chronic pulmonary disease before. After 6 cycles every three-week of postoperative adjuvant chemotherapy (pemetrexed, carboplatin), he sequentially received 50 GyE of IMPT in 25 fractions. About 7 weeks after IMPT, grade 2 RILI was developed with the manifestation of focal pulmonary consolidation and ground-glass attenuation. Steroid therapy was delivered and the pneumonias absorbed slightly with chronic scarring and fibrosis left over. Conclusions: RILI after IMPT is not commonplace especially under the circumstance where the patient had no chronic lung disease and the proton dose was conservative. The patient manifested as the early developed acute exudation and fibrosis stage. Moreover, the injury was so refractory that fibrosis was developing in spite of active steroid therapy. Based on the case, we suggested that more exploration of proton induced lung injury and evaluation before IMPT especially following chemotherapy are deserved.

Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Immunotherapies represented by immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. A large part of the population has both cancer and psoriasis but is usually excluded from ICI clinical trials because of the dysregulated activation of the immune system. This is the first study to evaluate the safety and efficacy of ICI therapy in patients with cancer and preexisting psoriasis. Methods: PubMed, EMBASE, Cochrane, and MEDLINE databases were searched from inception through February 2022. Observational studies on patients with cancer and confirmed psoriasis before ICI initiation were included. Outcomes included the incidence of psoriasis flares, de novo immune-related adverse events (irAEs), discontinuation rate due to flare/de novo irAEs, and efficacy of ICI therapy. Clinical manifestations, management, and outcomes for adverse events (AEs) were systematically reviewed. All pooled analyses were based on a random-effects model using Stata software. Meta-regression and subgroup analyses were performed to identify sources of heterogeneity. Results: Twelve studies involving 191 patients were included. The pooled incidence of psoriasis flares was 45.0% (95% CI: 31.1%-58.9%, I2 = 71.7%) and 44.9% (95% CI: 29.0%-60.7%, I2 = 71.8%) for de novo irAEs. The tumor type, psoriasis subtype, ICI class, and country were the main sources of heterogeneity. Grade 3-4 flares occurred in 10.8% (95% CI: 5.3%-16.3%) of patients, and about 16.6% (95% CI: 10.7%-22.5%) of patients experienced grade 3-4 de novo irAEs. The estimated incidence of ICI discontinuation due to AE was 18.5% (95% CI: 6.1%-30.8%, I2 = 68.7%). The median times to develop flare and de novo irAEs were 44 and 63 days, respectively. Endocrinopathies and colitis were the most common de novo irAEs. Conventional therapy is effective for most AEs. The estimated objective response rate (ORR) of ICIs was 38.1% (95% CI: 11.8%-64.3%, I2 = 81.7%), and the disease control rate (DCR) was 64.5% (95% CI: 55.3%-73.8%, I2 = 0). Conclusions: The flare of patients with cancer and preexisting psoriasis treated with ICI therapy is frequent, but the incidence of de novo irAEs and the efficacy of ICI therapy are comparable to those of the general population. Most AEs are mild and manageable with conventional therapy, which required discontinuation of ICI therapy in 18.5%. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022320646.

Hyper-Methylated Hub Genes of T-Cell Receptor Signaling Predict a Poor Clinical Outcome in Lung Adenocarcinoma.

Background: Immune checkpoint inhibitors (ICIs) emerge as the first-line treatment of lung adenocarcinoma (LUAD); selection of subpopulations acquiring clinical benefit is required. Associations between epigenetic modulation of tumor microenvironment (TME) and clinical outcome are far from clear. We focused on immune-related genes closely regulated by DNA methylation to identify the potential clinical outcome indicators. Methods: We systematically calculated immunophenotype score (IMpS) and classified immunophenotypes based on seven TME features in three independent cohorts. The overlapping of differential expressed genes and methylated probes targeted genes was regarded as genes closely regulated by DNA methylation. Then, probe/gene pairs which highly correlated with each other and IMpS were identified and named as immune-related probe/gene pairs (mIMg). Prognostic mIMg were selected and verified in seven independent validation cohorts. Results: Three immune phenotypes were clustered, and similar results were obtained in the three independent training cohorts. C2 displayed as an immunologically hot phenotype, whereas C3 corresponded with immunologically cold phenotype. Average methylation level was decreased from C2 to C3 (C2 > C1 > C3). Similarly, ICIs nonresponders showed global hypo-methylation compared with responders. Genes in mIMg were mainly enriched, especially in T-cell receptor activation, and repressed in noninflamed TME by hyper-methylation. Among mIMg, low expression and hyper-methylation of CD247, LCK, and PSTPIP1 were risk factors of overall survival (OS). ICIs nonresponders were more likely to be hyper-methylated in the three genes. By integrating with the oncogenes status, we demonstrated that EGFR wt and SRGN overexpressed patients were associated with chronic inflammation and immune evasion, showing an immunologically hot phenotype, which might lead to the short OS but derive clinical benefit from ICIs. Conclusions: This study identifies hyper-methylation and concurrent repression of CD247, LCK, PSTPIP1 as immune negative indicators and risk factors for prognosis in LUAD. Moreover, EGFR/SRGN axis may participate in immune modification to influence ICIs response and clinical outcome in LUAD.

[Screening of differentially expressed genes for colorectal cancer and prediction of potential traditional Chinese medicine: based on bioinformatics].

This study screened and analyzed the differentially expressed genes(DEGs) between colorectal cancer(CRC) tissues and normal tissues with bioinformatics techniques to predict biomarkers and Chinese medicinals for the diagnosis and treatment of CRC. The microarray data sets GSE21815, GSE106582, and GSE41657 were downloaded from the Gene Expression Omnibus(GEO), and the DEGs were screened by GEO2 R, followed by the Gene Ontology(GO) tern enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the DEGs based on DAVID. The protein-protein interaction network was constructed by STRING, and MCODE and Cytohubba plug-ins were used to screen the significant modules and hub genes in the network. UCSC, cBioPortal, and Oncomine were employed for hierarchical clustering, survival analysis, Oncomine analysis, and correlation analysis of clinical data. Coremine Medical was applied to predict the Chinese medicinals acting on hub genes. A total of 284 DEGs were screened out, with 146 up-regulated and 138 down-regulated. The up-regulated genes were mainly involved in cell cycle, NLRs pathway, and TNF signaling pathway, and the down-regulated genes were related to mineral absorption, nitrogen metabolism, and bicarbonate reabsorption in proximal tubules. The 15 hub genes were CDK1, CDC20, AURKA, MELK, TOP2 A, PTTG1, BUB1, CDCA5, CDC45, TPX2, NEK2, CEP55, CENPN, TRIP13, and GINS2, among which CDK1 and CDC20 were regarded as core genes. The high expression of CDK1 and CDC20 suggested poor prognosis, and they significantly expressed in many cancers, especially breast cancer, lung cancer, and CRC. The expression of CDK1 and CDC20 was correlated with gender, tumor type, TNM stage, and KRAS gene mutation. The potential effective medicinals against CRC were Scutellariae Radix, Scutellariae Barbatae Herba, Arnebiae Radix, etc. The significant expression of CDK1 and CDC20 can help distinguish tumor tissues from normal tissues, and is related to survival prognosis. Thus, the two can be used as biomarkers for the diagnosis and treatment of CRC. This study provides a reference for related drug development.

Implications of hydrogen peroxide on bromate depression during seawater ozonation.

The presence of hydrogen peroxide (H2O2) in ozonation process can resist the formation of carcinogenic bromate (BrO3¯) efficiently, and the bromate depression is closely related with background water qualities, especially in high bromide-containing seawater. In this study, the freshwater and seawater were selected to investigate the effects of H2O2 on ozone (O3) decomposition kinetics, bromide transformation and bromate depression, and the evolutions of BrO3¯ under different scavengers were explored to speculate the primary bromate formation pathways. The results showed that the initial O3 half-live period (t1/2-O3) in seawater was only one-sixth of that in freshwater, and its attenuation rate increased analogously with the increase of H2O2 concentration in both freshwater and seawater. The H2O2 could promote the formation of BrO3¯ via hydroxyl radical (•OH) based bromate pathways, nevertheless higher concentration of H2O2 facilitated the reduction of HOBr/OBr¯ back to Br¯, resulting in 87.0% and 73.2% of BrO3¯ retardment in freshwater and seawater, respectively. The suppression ratios of BrO3¯ were up to 48.4% and 35.3% in freshwater with the addition of •OH and •O2¯ scavengers, and the corresponding depressions in seawater decreased to 35.3% and 12.7%, indicating that •OH was dominant on bromate formation when the concentration of residual ozone was adequate to generate some bromine intermediates, meanwhile H2O2 and •O2¯ functioned as the key reductants for bromate depression. Based on these results, the Br¯ transformation mechanisms via O3, •OH, H2O2, and •O2¯ reactions were speculated, and the feasibility of H2O2-ozonation was verified for the treatment of high Br¯-containing seawater.

[Determination of 2-methylisoborneol and geosmin in drinking water using headspace solid phase micro-extraction coupled with gas chromatography-mass-spectrometry].

The odorous compounds of 2-methylisoborneol (2-MIB) and geosmin (GSM) heavily produced and released in water source are one of the most important factors leading to off-flavor emergencies and resident water consumption panic in drinking water. A headspace solid phase micro-extraction ( HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) method was established for the simultaneous determination of these two trace earthy and musty compounds in reservoir water, reservoir soil and tap water. The conditions of HS-SPME, such as salt amount, extraction time and extraction temperature, were optimized based on orthogonal analysis. The qualitative and quantitative analyses of 2-MIB and GSM were carried out in the electron impact (EI) -selective ion scanning mode. The results showed that the linear relationship between peak area and concentration of 2-MIB and GSM was good enough (r2 0.998) from 5 to 1 000 ng/L, the limits of detection were 0.72 ng/L for 2-MIB, 0.34 ng/L for GSM and the limits of quantification were 2.40 ng/L for 2-MIB, 1.13 ng/L for GSM. When the target samples spiked in the range of 10-600 ng/L, the average recoveries of the target compounds were 93.6% - 107.7% ( RSD ≤ 6.1%, n = 6). Based on the above method, the target compounds in reservoir water, reservoir soil and tap water in a certain region of Liaoning Province were analyzed. The results showed that the two target odors in reservoir water were 3.0 -3.6 ng/L. As for the extract of the soil around the reservoir, 2-MIB was 8.1 ng/L and GSM was 17.8 ng/L. The odorous substances were not detected in the tap water. This method is simple, accurate, reliable, highly sensitive and no need of organic solvents. And it is suitable for the detection of 2-MIB and GSM in drinking water.