A meta-analysis highlights the cross-resistance of plants to drought and salt stresses from physiological, biochemical, and growth levels.

In nature, drought and salt stresses often occur simultaneously and affect plant growth at multiple levels. However, the mechanisms underlying plant responses to drought and salt stresses and their interactions are still not fully understood. We performed a meta-analysis to compare the effects of drought, salt, and combined stresses on plant physiological, biochemical, morphological and growth traits, analyze the different responses of C3 and C4 plants, as well as halophytes and non-halophytes, and identify the interactive effects on plants. There were numerous similarities in plant responses to drought, salt, and combined stresses. C4 plants had a more effective antioxidant defense system, and could better maintain above-ground growth. Halophytes could better maintain photosynthetic rate (Pn) and relative water content (RWC), and reduce growth as an adaptation strategy. The responses of most traits (Pn, RWC, chlorophyll content, soluble sugar content, H2O2 content, plant dry weight, etc.) to combined stress were less-than-additive, indicating cross-resistance rather than cross-sensitivity of plants to drought and salt stresses. These results are important to improve our understanding of drought and salt cross-resistance mechanisms and further induce resistance or screen-resistant varieties under stress combination.

Irisin alters D-galactose-induced apoptosis by increasing caveolin-1 expression in C2C12 myoblasts and skeletal muscle fibroblasts.

Muscle atrophy and skeletal muscle fibrosis are significant pathological manifestations of primary sarcopenia. The regulation of C2C12 myoblast and skeletal muscle fibroblast apoptosis is associated with these pathological changes. Previous studies have indicated that irisin, the cleaved form of fibronectin type III domain-containing protein 5 (FNDC5), can alleviate primary sarcopenia. However, the mechanisms of the effect of irisin in age-related apoptosis remain unknown. Our present research aimed to explore the effect of irisin and the underlying mechanism of D-galactose (D-gal)-induced apoptosis in skeletal muscle fibroblasts and C2C12 myoblasts. We found the opposite effects of D-gal on C2C12 myoblasts and fibroblasts. We also found that irisin suppressed C2C12 cell apoptosis and promoted fibroblast apoptosis. Mechanistically, irisin altered D-gal-induced apoptosis by increasing caveolin-1 expression. Taken together, these findings further demonstrated that irisin is a potential agent that can treat aged-relative muscle atrophy and fibrosis.

A novel derivative synchronous fluorescence method for the rapid, non-destructive and intuitive differentiation of denitrifying bacteria.

It is challenging to differentiate bacteria residing in the same habitat by direct observation. This difficulty impedes the harvest, application and manipulation of functional bacteria in environmental engineering. In this study, we developed a novel method for rapid differentiation of living denitrifying bacteria based on derivative synchronous fluorescence spectroscopy, as exemplified by three heterotrophic nitrification-aerobic denitrification bacteria having the maximum nitrogen removal efficiencies greater than 90%. The intact bacteria and their living surroundings can be analyzed as an integrated target, which eliminates the need for the complex pre-processing of samples. Under the optimal synchronous scanning parameter (Δλ = 40 nm), each bacterium possesses a unique fluorescence spectral structure and the derivative synchronous fluorescence technique can significantly improve the spectral resolution compared to other conventional fluorescence methods, which enables the rapid differentiation of different bacteria through derivative synchronous fluorescence spectra as fast as 2 min per spectrum. Additionally, the derivative synchronous fluorescence technique can extract the spectral signals contributed by bacterial extracellular substances produced in the biological nitrogen removal process. Moreover, the results obtained from our method can reflect the real-time denitrification properties of bacteria in the biological nitrogen removal process of wastewater. All these merits highlight derivative synchronous fluorescence spectroscopy as a promising analytic method in the environmental field.

Elevated CO2 concentration increases maize growth under water deficit or soil salinity but with a higher risk of hydraulic failure.

Climate change presents a challenge for plants to acclimate their water relations under changing environmental conditions, and may increase the risks of hydraulic failure under stress. In this study, maize plants were acclimated to two different CO2 concentrations ([CO2]; 400 ppm and 700 ppm) while under either water stress (WS) or soil salinity (SS) treatments, and their growth and hydraulic traits were examined in detail. Both WS and SS inhibited growth and had significant impacts on hydraulic traits. In particular, the water potential at 50% loss of stem hydraulic conductance (P50) decreased by 1 MPa in both treatments at 400 ppm. When subjected to elevated [CO2], the plants under both WS and SS showed improved growth by 7-23%. Elevated [CO2] also significantly increased xylem vulnerability (measured as loss of conductivity with decreasing xylem pressure), resulting in smaller hydraulic safety margins. According to the plant desiccation model, the critical desiccation degree (time×vapor pressure deficit) that the plants could tolerate under drought was reduced by 43-64% under elevated [CO2]. In addition, sensitivity analysis showed that P50 was the most important trait in determining the critical desiccation degree. Thus, our results demonstrated that whilst elevated [CO2] benefited plant growth under WS or SS, it also interfered with hydraulic acclimation, thereby potentially placing the plants at a higher risk of hydraulic failure and increased mortality.

Unusual rearrangements of mitogenomes in Diptera revealed by comparative analysis of 135 tachinid species (Insecta, Diptera, Tachinidae).

The Tachinidae is one of the most speciose families in Diptera, and the exclusively parasitoid species play an important role in regulating populations of many herbivorous insects in ecosystems, including many agricultural pests. To better comprehend the characteristics and evolution of the mitochondrial genome for the Tachinidae, we are adding a massive amount of new molecular data by assembling the mitogenomes for 71 genera and 135 species from all four tachinid subfamilies through next-generation sequencing, and we are presenting the most comprehensive mitogenomic phylogenetic analysis of this family so far. Extensive rearrangements observed in the mitogenome of Admontia podomyia (Exoristinae) are unique for the entire suborder Cyclorrhapha. The rearrangement pattern suggests that the process involved a tandem duplication of the complete mitogenome, followed by both random and nonrandom loss of one copy of each gene. Additionally, five minor mitogenome rearrangements are discovered and described in three subfamilies. We present the largest species-level phylogenetic hypothesis for Tachinidae to date, based on mitogenomes of 152 species of Tachinidae, representing all four subfamilies and with five non-tachinid outgroups. Our analyses support the monophyly of the Tachinidae and most tribes and genera were recovered with good support, but the higher-level phylogenetic relationships within Tachinidae were poorly resolved, indicating that mitogenome data alone are not enough to unambiguously resolve the deeper phylogenetic relationships within Tachinidae.

Predictive Value of EGFR Mutation Status for First-Line Tyrosine Kinase Inhibitor Treatment in Patients with Advanced Lung Cancer.

Objective: This study aims to investigate and analyze the correlation between EGFR-TKI first-line therapy and EGFR mutation status in patients with advanced lung cancer. Methods: We selected 60 patients with advanced lung cancer and EGFR mutations (diagnosed as stage IIIb or IV) from our hospital between January 2019 and November 2022. Each patient underwent an EGFR mutation test and was categorized into two groups based on their mutation status: 28 patients with exon 21 mutations and 32 with exon 19 deletions. After three months of therapy, we assessed treatment efficacy and adverse reactions. Results: Our data revealed that in the EGFR exon 21 mutation group, the objective response rate (ORR) and disease control rate (DCR) were 57.14% and 60.71%, respectively. In the EGFR exon 19 deletion group, the ORR and DCR were 68.75% and 84.38%, respectively. There were significant differences in DCR and ORR between the two EGFR mutation states, with statistical significance (P < .05). The progression-free survival (PFS) in the EGFR exon 21 mutant group was 8.4 months after third-generation EGFR-TKI treatment, while the EGFR exon 19 deletion group had a PFS of 12.7 months after the same treatment, with a statistically significant difference (P < .05). Cox regression analysis showed that female patients with no smoking history and an adenocarcinoma pathological type had significantly better PFS after treatment compared to male patients with a smoking history and squamous cell carcinoma type, with statistical significance (P < .05). Age and clinical stage did not significantly impact PFS after third-generation EGFR-TKI treatment (P > .05). Adverse reaction incidences, such as nausea, fatigue, diarrhea, vomiting, and rash, did not significantly differ in either the EGFR exon 21 mutation group or the EGFR exon 19 deletion group (P > .05). Conclusion: The status of EGFR mutations serves as a predictive factor for PFS, DCR, and ORR in lung cancer patients undergoing EGFR-TKI first-line therapy. This status can be a valuable predictive indicator of lung cancer treatment efficacy, with potential applications in clinical practice.

In silico prediction of bioequivalence of atorvastatin tablets based on GastroPlus™ software.

The prediction of intestinal absorption of various drugs based on computer simulations has been a reality. However, in vivo pharmacokinetic simulations and virtual bioequivalence evaluation based on GastroPlus™ have not been found. This study aimed to simulate plasma concentrations with different dissolution profiles and run population simulations to evaluate the bioequivalence of test and reference products of atorvastation using GastroPlus software. The dissolution profiles of the reference and test products of atorvastatin (20 mg tablets), and clinical plasma concentration-time data of the reference product were used for the simulations. The results showed that the simulated models were successfully established for atorvastatin tablets. Population simulation results indicated that the test formulation was bioequivalent to the reference formulation. The findings suggest that modelling is an essential tool to demonstrating the possibility of pharmacokinetic and bioequivalence for atorvastatin. It will contribute to understanding the potential risks during the development of generic products.

Bioequivalence Study of Epalrestat for Healthy Chinese Subjects.

Epalrestat is a reversible noncompetitive inhibitor of aldose reductase with selective inhibition of aldose reductase. It can inhibit the accumulation of sorbitol in red blood cells in patients with diabetic peripheral neuropathy and can improve patients' conscious symptoms and neurological dysfunction. This study was designed to evaluate the bioequivalence in healthy Chinese subjects of a new test formulation and reference formulation of oral epalrestat (50 mg) in the fasting state. The study was performed with 44 healthy Chinese subjects according to a randomized 2-way crossover design. The main pharmacokinetic parameters of test formulation and reference formulation as follows: 4793 and 4781 ng/mL for maximum plasma concentration, 8556 and 8431 ng h/mL for area under the plasma concentration-time curve extrapolated to infinity. The test formulation of epalrestat was bioequivalent to the reference formulation. The bioequivalence study of epalrestat in healthy Chinese subjects suggests that the test and reference formulations have similar pharmacokinetics and both formulations are well tolerated in the dose range studied in healthy Chinese subjects. All these findings provided valuable pharmacokinetic knowledge for further clinical development.

The Clinical Relevance and Functional Implications of Thymosin Beta-10 in Glioma.

Glioma is a highly aggressive form of brain cancer characterized by limited treatment options and poor patient prognosis. In this study, we aimed to elucidate the oncogenic role of thymosin beta-10 (TMSB10) in glioma through comprehensive analyses of patient data from the TCGA and GTEx databases. Our investigation encompassed several key aspects, including the analysis of patients' clinical characteristics, survival analysis, in vitro and in vivo functional experiments, and the exploration of correlations between TMSB10 expression and immune cell infiltration. Our findings revealed a significant upregulation of TMSB10 expression in glioma tissues compared to normal brain tissues, with higher expression levels observed in tumors of advanced histological grades. Moreover, we observed positive correlations between TMSB10 expression and patient age, while no significant association with gender was detected. Additionally, TMSB10 exhibited marked elevation in gliomas with wild-type IDH and noncodeletion of 1p/19q. Survival analysis indicated that high TMSB10 expression was significantly associated with worse overall survival, disease-specific survival, and progression-free survival in glioma patients. Functionally, knockdown of TMSB10 in glioma cells resulted in reduced cellular growth rates and impaired tumor growth in xenograft models. Furthermore, our study revealed intriguing correlations between TMSB10 expression and immune cell infiltration within the tumor microenvironment. Specifically, TMSB10 showed negative associations with plasmacytoid dendritic cells (pDC) and γδ T cells (Tgd), while displaying positive correlations with neutrophils and macrophages. These findings collectively provide valuable insights into the oncogenic properties of TMSB10 in glioma, suggesting its potential as a therapeutic target and a biomarker for patient stratification.

L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome.

Model-assisted analysis for tuning anthocyanin composition in grape berries.

Anthocyanin composition is responsible for the red colour of grape berries and wines, and contributes to their organoleptic quality. However, anthocyanin biosynthesis is under genetic, developmental and environmental regulation, making its targeted fine-tuning challenging. We constructed a mechanistic model to simulate the dynamics of anthocyanin composition throughout grape ripening in Vitis vinifera, employing a consensus anthocyanin biosynthesis pathway. The model was calibrated and validated using six datasets from eight cultivars and 37 growth conditions. Tuning the transformation and degradation parameters allowed us to accurately simulate the accumulation process of each individual anthocyanin under different environmental conditions. The model parameters were robust across environments for each genotype. The coefficients of determination (R2) for the simulated versus observed values for the six datasets ranged from 0.92 to 0.99, while the relative root mean square errors (RRMSEs) were between 16.8 and 42.1 %. The leave-one-out cross-validation for three datasets showed R2 values of 0.99, 0.96 and 0.91, and RRMSE values of 28.8, 32.9 and 26.4 %, respectively, suggesting a high prediction quality of the model. Model analysis showed that the anthocyanin profiles of diverse genotypes are relatively stable in response to parameter perturbations. Virtual experiments further suggested that targeted anthocyanin profiles may be reached by manipulating a minimum of three parameters, in a genotype-dependent manner. This model presents a promising methodology for characterizing the temporal progression of anthocyanin composition, while also offering a logical foundation for bioengineering endeavours focused on precisely adjusting the anthocyanin composition of grapes.

Physiologically based pharmacokinetic modeling to characterize enterohepatic recirculation and predict food effect on the pharmacokinetics of hyzetimibe.

BACKGROUND AND OBJECTIVE: Hyzetimibe is a cholesterol absorption inhibitor indicated for the treatment of hypercholesterolemia. This study aims to describe the multiple-peak pharmacokinetics (PK) of hyzetimibe and its active metabolite M1 through physiologically-based pharmacokinetic (PBPK) modeling, and to compare the model predictions of a virtual food effect study with the results of a clinical food effect study. METHODS: The plasma concentration data used for PBPK modeling were obtained from a single-dose, two-period crossover bioequivalence study in the fasted state. Advanced Compartmental Absorption and Transit model was used for absorption. Enterohepatic recirculation process was modeled by changing the gut physiological state from fasted to fed at meal time. Based on the established PBPK models, a virtual food effect study was simulated. A clinical food effect study was used for model external validation. RESULTS: PK profiles of hyzetimibe and M1 under fasting condition could be well described by the PBPK model, and the errors of Cmax, AUC0-∞, and AUC0-t were within the two-fold range. Simulated geometric mean ratios (GMRs, fed/fasted) showed that a high-fat breakfast slightly affected the PK of hyzetimibe, expressed as increased Cmax of hyzetimibe (130.6%). Simulated GMRs and 90% confidence intervals of AUC were within the preset bioequivalent range. The results of the simulated virtual food effect trial were consistent with those of the clinical food effect trial. CONCLUSIONS: The established PBPK model could describe the concentration-time profiles of hyzetimibe and M1 well with good prediction performance. A fully mechanistic model of enterohepatic recirculation warrants further investigation.

Physiologically based absorption modeling to predict the bioequivalence of two cilostazol formulations.

In vivo pharmacokinetic simulations and virtual bioequivalence (BE) evaluation of cilostazol have not yet been described for humans. Here, we successfully developed a physiologically based absorption model to simulate plasma concentrations of cilostazol. In addition, virtual population simulations integrating dissolution of 0.3% sodium dodecyl sulfate water media were executed to evaluate the BE of test and reference formulations. Simulation results show that test and reference formulations were bioequivalent among 28 subjects, but not nine subjects, consistent with clinical studies. The model proved to be an important tool to show potential BE for cilostazol. This finding may facilitate understanding of the potential risks during the development of generic products.

Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and concurrent mutations have a poor prognosis. This study aimed to examine anlotinib plus icotinib as a first-line treatment option for advanced NSCLC carrying EGFR mutation with or without concurrent mutations. METHODS: This phase 2, single-arm, multicenter trial (ClinicalTrials.gov NCT03736837) was performed at five hospitals in China from December 2018 to November 2020. Non-squamous NSCLC cases with EGFR-sensitizing mutations were treated with anlotinib and icotinib. The primary endpoint was progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. RESULTS: Sixty participants were enrolled, including 31 (52%) and 29 (48%) with concurrent mutations and pathogenic concurrent mutations, respectively. The median follow-up was 26.9 (range, 15.0-38.9) months. ORR and DCR were 68.5% and 98.2%, respectively. Median PFS was 15.1 (95%CI: 12.6-17.6) months which met the primary endpoint, median DoR was 13.5 (95%CI: 10.0-17.1) months, and median OS was 30.0 (95%CI: 25.5-34.5) months. Median PFS and OS in patients with pathogenic concurrent mutations were 15.6 (95%CI: 12.5-18.7) months and not reached (95%CI: 17.46 months to not reached), respectively. All patients experienced TRAEs, including 26 (43%) and 1 (1.7%) who had grade ≥ 3 and serious treatment-related adverse events (TRAEs). CONCLUSIONS: Anlotinib combined with icotinib was effective and well-tolerated as a first-line treatment option for EGFR mutation-positive advanced NSCLC with or without concurrent mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03736837.

Triad3A involved in the regulation of endotoxin tolerance and mycobactericidal activity through the NFκB-nitric oxide pathway.

INTRODUCTION: Sepsis is characterized by an endotoxin tolerance phenotype that occurs in the stage of infection. Persistent bacterial infection can lead to immune cell exhaustion. Triad3A, an E3 ubiquitin ligase, negatively regulates its activation by TLR4. However, the effect of Triad3A on endotoxin tolerance and bactericidal ability in the state of endotoxin tolerance remains unclear. METHODS: Using single dose LPS and repeated LPS stimulated macrophage cell lines at indicated times, we investigated miR-191, Tirad3A, TRAF3, TLR4, p-P65, TNF-α, IL-1ß, and iNOS expression, the effect of miR-191 on Triad3A and TRAF3, gene loss-of-function analyses, the effect of Triad3A on TLR4, p-P65, cytokine, and mycobactericidal activity in endotoxin tolerant cells infected with Mycobacterium marinum. RESULTS: Here we found that Triad3A is involved in regulating endotoxin tolerance. Our result also displayed that miR-191 expression is downregulated in macrophages in the state of endotoxin tolerance. miR-191 can directly bind to Triad3A and TRAF3. Additionally, knockdown of Triad3A can reverse the effect of decreasing TNF-α and IL-1ß in endotoxin tolerant macrophages. Furthermore, we demonstrated that the TLR4-NF-κB-NO pathway was associated with Triad3A and responsible for the killing of intracellular mycobacteria in a tuberculosis sepsis model. CONCLUSIONS: These results provide new insight into the mechanisms of Triad3A induced tolerogenic phenotype in macrophages, which can help the better comprehension of the pathogenesis involved in septic shock with infection of Mycobacterium tuberculosis, and suggest that Triad3A may be a potential drug target for the treatment of severe septic tuberculosis.

[Corrigendum] Role of the EZH2/miR­200 axis in STAT3­mediated OSCC invasion.

Following the publication of the above article, an interested reader drew to the authors' attention that, in Figs. 7A and 8A. apparently the same mouse had been featured to represent two different experimental groups, albeit displaying distinct fluorescence values. Moreover, following an independent investigation in the Editorial Office, an additional instance of probable data duplication was also noted, comparing between the 'SCC15 / si­NC' cell migration image in Fig. 2D and the 'SCC15­EV' migration assay image in Fig. 1C. After having consulted their original data, the authors realized that these errors arose during the process of assembling the images for Figs. 2 and 8. First, the image for the DZNep (42d) experiment in Fig. 7A had inadvertently been used for the mimic NC (7d) experiment in Fig. 8A; moreover, the 'SCC15 / si­NC' cell migration image in Fig. 2D had been selected incorrectly. The revised versions of Figs. 2 and 8, showing the correct data for the the 'SCC15 / si­NC' cell migration image in Fig. 2D and the mimic NC (7d) experiment in Fig. 8A, are shown on the next two pages. The authors regret that these errors went unnoticed prior to publication, and thank the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 52: 1149­1164, 2018; DOI: 10.3892/ijo.2018.4293].

Clinical outcome analysis of modified B-Lynch sutures in the fundus uteri and part of the corpus uteri for the prevention of intraoperative haemorrhage during caesarean delivery in women with twin pregnancy: a retrospective study.

OBJECTIVE: To explore the efficacy of modified B-Lynch sutures in the fundus uteri and part of the corpus uteri for the prevention of intraoperative haemorrhage during caesarean delivery in women with twin pregnancy. METHODS: This retrospective analysis covers the clinical data of 40 women with postpartum haemorrhage caused by uterine inertia during caesarean section in women with twin pregnancy in our hospital from January 2018 to May 2022. These women were divided into the group with modified B-Lynch sutures at the fundus and part of the corpus uteri (Group A, 20 patients) and the group with classic B-Lynch sutures (Group B, 20 patients) according to the treatment received. The treatment effect and safety of the two uterine compression sutures were compared. RESULTS: In this study, no statistically significant differences were found in the outcomes of haemostasis or intraoperative and 24-h postoperative blood loss between the two uterine compression suture groups (P > 0.05). Compared to Group B, Group A showed a significantly reduced operative time, postoperative hospital stay, puerperal morbidity rate, pain score and duration of lochia. CONCLUSION: Modified B-Lynch sutures at the fundus and part of the corpus uteri can achieve a haemostatic effect similar to that of the classic B-Lynch suture, while it allows for a shortened operative time and reduced postoperative complications. Modified B-Lynch sutures can serve as a safe, rapid and effective haemostatic method for the prevention and treatment of postpartum haemorrhage during caesarean section in women with twin pregnancy, showing certain validity for promotion in clinics.

The response prediction and prognostic values of systemic inflammation response index in patients with advanced lung adenocarcinoma.

PURPOSE: This study aimed to assess the response prediction and prognostic values of different peripheral blood cell biomarkers for advanced lung adenocarcinoma (LUAD) patients receiving first-line therapy. METHODS: Patients diagnosed with advanced LUAD as well as healthy controls and patients with benign pulmonary diseases were collected in this retrospective study. Propensity score matching (PSM) was performed in a 1:1 ratio. Survival state was estimated by the Kaplan-Meier method and the Cox proportional hazard model was used to assess the prognostic factors. RESULTS: Compared with the control groups, the level of peripheral blood leucocyte, neutrophil, monocyte, platelet, and neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, platelet to lymphocyte ratio, and systemic inflammation response index (SIRI) were higher in LUAD patients (all p < 0.001). Some inflammatory markers decreased at the time of optimal response and then increased again as the disease progressed. Multivariate analysis revealed that SIRI and lactate dehydrogenase (LDH) were independent prognostic factors no matter before or after PSM analysis. Area under the curve (AUC) of SIRI and LDH were 0.625 (p < 0.001) and 0.596 (p = 0.008), respectively. When SIRI and LDH were combined, the AUC reached 0.649 (p < 0.001). CONCLUSIONS: Pretreatment SIRI was an independent prognostic factor of progression free survival (PFS) in advanced LUAD patients. Dynamic monitoring of inflammatory index changes could help to predict therapeutic efficacy. The combination of SIRI and LDH is expected to be a promising clinically accessible biomarker in the future.

Palladium-loaded ceramic membrane-catalyzed flow-through Suzuki-Miyaura reaction.

A general Pd-loaded ceramic membrane catalyzed Suzuki-Miyaura reaction in a flow-through membrane reactor is reported for the first time. Versatile (hetero)aryl bromides and chlorides proceeded well with an array of (hetero)aryl boronic acids. The consistently high activity of the catalytic membrane in eight cycles has proved its good stability and recyclability. Synthesis of drug molecules has further demonstrated that the catalytic membrane protocol is a powerful and comprehensive alternative to the traditional Suzuki-Miyaura cross-coupling.