Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells.

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.

Co(III)-Catalyzed C6-Selective C-H Activation/Pyridine Migration of 2-Pyridones with Propiolates.

A versatile Co(III)-catalyzed C6-selective C-H activation/pyridine migration of 2-pyridones with available propiolates as coupling partners was demonstrated. This method features high atom economy, excellent regioselectivity, and good functional group tolerance by employing an inexpensive Co(III) catalyst under mild reaction conditions. Moreover, gram-scale synthesis and late-stage modifications of pharmaceuticals were performed to prove the effectiveness of these synthetic approaches.

Chinese expert consensus recommendations for the administration of immune checkpoint inhibitors to special cancer patient populations.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4 have shown significantly durable clinical benefits and tolerable toxicities and have improved the survival of patients with various types of cancer. Since 2018, the National Medical Products Administration of China has approved 17 ICIs as the standard treatment for certain advanced or metastatic solid tumors. As ICIs represent a broad-spectrum antitumor strategy, the populations eligible for cancer immunotherapy are rapidly expanding. However, the clinical applications of ICIs in cancer patient populations with special issues, a term that refers to complex subgroups of patients with comorbidities, special clinical conditions, or concomitant medications who are routinely excluded from prospective clinical trials of ICIs or are underrepresented in these trials, represent a great real-world challenge. Although the Chinese Society of Clinical Oncology (CSCO) has provided recommendations for screening before the use of ICIs in special populations, the recommendations for full-course management remain insufficient. The CSCO Expert Committee on Immunotherapy organized leading medical oncology and multidisciplinary experts to develop a consensus that will serve as an important reference for clinicians to guide the proper application of ICIs in special patient populations. This article is a translation of a study first published in Chinese in The Chinese Clinical Oncology (ISSN 1009-0460, CN 32-1577/R) in May 2022 (27(5):442-454). The publisher of the original paper has provided written confirmation of permission to publish this translation in Therapeutic Advances in Medical Oncology.

Evaluation of bladder filling effects on the dose distribution during radiotherapy for cervical cancer based on daily CT images.

PURPOSE: This study aimed to assess the effects of bladder filling during cervical cancer radiotherapy on target volume and organs at risk (OARs) dose based on daily computed tomography (daily-CT) images and provide bladder-volume-based dose prediction models. METHODS: Nineteen patients (475 daily-CTs) comprised the study group, and five patients comprised the validation set (25 daily-CTs). Target volumes and OARs were delineated on daily-CT images and the treatment plan was recalculated accordingly. The deviation from the planning bladder volume (DVB), the correlation between DVB and clinical (CTV)/planning (PTV) target volume in terms of prescribed dose coverage, and the relationship of small bowel volume and bladder dose with the ratio of bladder volume (RVB) were analyzed. RESULTS: In all cases, the prescribed dose coverage in the CTV was >95% when DVB was <200 cm3 , whereas that in the PTV was >95% when RVB was <160%. The ratio of bladder V45 Gy to the planning bladder V45 Gy (RBV45 ) exhibited a negative linear relationship with RVB (RBV45  = -0.18*RVB + 120.8; R2  = 0.80). Moreover, the ratio of small bowel volume to planning small bowel volume (RVS) exhibited a negative linear relationship with RVB (RVS = -1.06*RVB +217.59; R2  = 0.41). The validation set results showed that the linear model predicted well the effects of bladder volume changes on target volume coverage and bladder dose. CONCLUSIONS: This study assessed dosimetry and volume effects of bladder filling on target and OARs based on daily-CT images. We established a quantitative relationship between these parameters, providing dose prediction models for cervical cancer radiotherapy.

Palladium(II)-Catalyzed Remote meta-C-H Functionalization of Arenes Enabled by Multitasking Oxyamides as the Linker.

A palladium-catalyzed olefination of meta-C-H bonds in arenes containing oxyamides using a nitrile template as the directing group has been established. The methodology exhibited high meta-selectivity and tolerated different functional groups such as benzyloxyamides and olefin substrates. The desired products were obtained in good yields. This approach enabled the modification of natural products and drugs and was also applicable on the gram-scale. Furthermore, the directing template was readily removed by selective cleavage of the amide bond or the O-N bond to obtain meta-functionalized hydroxylamines and benzyl alcohols. The proposed method holds great potential for the design of novel drugs.

Spectral analysis of multiple scattering factors of turbid media for glucose measurement using near-infrared spectroscopy.

Significance: Near-infrared (NIR) diffuse reflectance spectroscopy has been widely used for non-invasive glucose measurement in humans, as glucose can induce a significant and detectable optical signal change in tissue. However, the scattering-dominated glucose spectrum in the range of 1000 to 1700 nm is easily confused with many other scattering factors, such as particle density, particle size, and tissue refractive index. Aim: Our aim is to identify the subtle distinctions between glucose and these factors through theoretical analysis and experimental verification, in order to employ suitable methods for eliminating these interferences, thus increasing the accuracy of non-invasive glucose measurement. Approach: We present a theoretical analysis of the spectra of 1000 to 1700 nm for glucose and some scattering factors, which is then verified by an experiment on a 3% Intralipid solution. Results: We found that both the theoretical and experimental results show that the effective attenuation coefficient of glucose has distinct spectral characteristics, which are distinct from the spectra caused by particle density and refractive index, particularly in the range of 1400 to 1700 nm. Conclusions: Our findings can offer a theoretical foundation for eliminating these interferences in non-invasive glucose measurement, aiding mathematical methods to model appropriately and enhance the accuracy of glucose prediction.

Effects of sleep quality on suicide risk in COVID-19 patients: The chain mediating of anxiety and depressive symptoms.

Background: Although current studies have identified sleep disorders as an independent risk factor for suicide, the relationship between sleep disorders and suicide risk has not been well established. This study explored whether anxiety and depressive symptoms are used as mediators to participate in the impact of sleep quality on suicide risk. Methods: This is a cross-sectional study. We administered a psychological questionnaire to the participants, using a combination of self-assessment and psychiatrist assessment.Sleep quality, suicide risk, level of anxiety and depressive symptoms were assessed by PSQI, NGASR, SAS and SDS.The study subjects were 391 hospitalized COVID-19 patients from Wuhan hospitals. We used model 6 in the PROCESS (version 3.5) plug-in of SPSS software to conduct mediation test with sleep quality as the independent variable, suicide risk as the dependent variable, level of anxiety and depressive symptoms as intermediate variables. Results: The severity of anxiety and depressive symptoms and the risk of suicide in the sleep disorder group (63.15 ± 13.71, 59.85 ± 13.38, 6.52 ± 3.67) were higher than those in the non-sleep disorder group (49.83 ± 13.14, 44.87 ± 10.19, 2.87 ± 3.26) (P < 0.001). The mediation model works well, The total indirect effect was 0.22 (95%CI = [0.17, 0.28]), and the direct effect was 0.16 (95%CI = [0.08, 0.24]). Limitations: This study used a self-assessment scale. Conclusions: Anxiety and depressive symptoms played a chain mediating role between sleep quality and suicide risk.

Integration of Handheld Ultrasound or Automated Breast Ultrasound among Women with Negative Mammographic Screening Findings: A Multi-center Population-based Study in China.

RATIONALE AND OBJECTIVES: This study assessed the role of second-look automated breast ultrasound (ABUS) adjunct to mammography (MAM) versus MAM alone in asymptomatic women and compared it with supplementing handheld ultrasound (HHUS). MATERIALS AND METHODS: Women aged 45 to 64 underwent HHUS, ABUS, and MAM among six hospitals in China from 2018 to 2022. We compared the screening performance of three strategies (MAM alone, MAM plus HHUS, and MAM plus ABUS) stratified by age groups and breast density. McNemar's test was used to assess differences in the cancer detection rate (CDR), the false-positive biopsy rate, sensitivity, and specificity of different strategies. RESULTS: Of 19,171 women analyzed (mean [SD] age, 51.54 [4.61] years), 72 cases of breast cancer (3.76 per 1000) were detected. The detection rates for both HHUS and ABUS combined with MAM were statistically higher than those for MAM alone (all p < 0.001). There was no significant difference in cancer yields between the two integration strategies. The increase in CRD of the integrated strategies was higher in women aged 45-54 years with denser breasts compared with MAM alone (all p < 0.0167). In addition, the false-positive biopsy rate of MAM plus ABUS was lower than that of MAM plus HHUS (p = 0.025). Moreover, the retraction in ABUS was more frequent in cases detected among MAM-negative results. CONCLUSION: Integrated ABUS or HHUS into MAM provided similar CDRs that were significantly higher than those for MAM alone in younger women (45-54 years) with denser breasts. ABUS has the potential to avoid unnecessary biopsies and provides specific image features to distinguish malignant tumors from HHUS.

Visualization of RNA Transcripts in Muscle Stem Cells Using Single-Molecule Fluorescence In Situ Hybridization.

Uncovering the transcriptomic signatures of quiescent muscle stem cells elicits the regulatory networks on stem cell quiescence. However, the spatial clues of the transcripts are missing in the commonly used quantitative analysis such as qPCR and RNA-seq. Visualization of RNA transcripts using single-molecule in situ hybridization provides additional subcellular localization clues to understanding gene expression signatures. Here, we provide an optimized protocol of smFISH analysis on Fluorescence-Activated Cell Sorting isolated muscle stem cells to visualize low-abundance transcripts.

Exogenous melatonin alleviates neuropathic pain-induced affective disorders by suppressing NF-κB/ NLRP3 pathway and apoptosis.

In this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e., Sham-VEH: healthy animals received a vehicle, Sham-MLT (10 mg/kg), and chronic constrictive injury (CCI)-VEH: nerve ligation received the vehicle, and CCI-MLT. Next, we used behavioral tests to evaluate pain severity, anxiety, and depression. Finally, rats were sacrificed for molecular and histopathological studies. Behavioral tests showed that NP could induce depressive- and anxiety-like behaviors. NP activated NF-κB/NLRP3 inflammasome pathways by upregulating NF-κB, NLRP3, ASC, active Caspase-1, also enhancing the concentrations of cytokines (IL-1ß and IL-18) in the prefrontal cortex (PFC) and hippocampus (HC). NP upregulated Bax, downregulated Bcl2, and increased cell apoptosis in the HC and PFC. The rats treated with MLT eliminated the effects of NP, as the reduced pain severity, improved anxiety- and depressive-like behaviors, ameliorated NF-κB/NLRP3 inflammasome pathways, and modulated levels of cytokines in the HC and PFC. MLT could promote cell survival from apoptosis by modulating Bax and Bcl2. Therefore, it might be inferred that its anti-inflammatory and anti-apoptotic properties mediate the beneficial effects of MLT in NP-induced affective disorders.

The value of ultrasound-guided fine needle aspiration in the diagnosis of diffuse large B-cell lymphoma: A single center experiment.

OBJECTIVES: Flow cytometry (FC) is a critical diagnostic approach for guiding targeted chemotherapy and cellular immunotherapy for relapsed and refractory lymphoma patients. The aim of the study was to investigate the value of ultrasound-guided fine needle aspiration (FNA) to improve the quality of FC specimens in relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL). METHODS: Twenty patients with R/R DLBCL after standard treatment were included. The primary lesions of all cases were confirmed by pathology. FNA and core needle biopsy (CNB) were both used for ultrasound-guided puncture, the specimens obtained by FNA are directly examined by FC, and the specimens by CNB were subjected to FC after grinding. The accuracy of FC with the two methods were evaluated using histopathology as the gold standard. RESULTS: Of the 20 R/R DLBCL cases, 19 were diagnosed as DLBCL pathologically and one was diagnosed as inflammatory granuloma. Among the specimens obtained by CNB, 14 cases examined by FC after grinding showed abnormal mature B cells, five cases were missed, all cases are not misdiagnosed. Among the specimens obtained by FNA, 18 cases showed FC-confirmed abnormal mature B cells, one case was missed, all cases are not misdiagnosed. The sensitivity, specificity, and accuracy of FC with CNB and FNA were 73.68 % (14/19) vs 94.73 % (18/19), 100 % (1/1) vs 100 % (1/1), and 75 % (15/20) vs 97.14 % (19/20), respectively. The sensitivity of the two puncture methods of FC of DLBCL was statistically different (p < 0.001). CONCLUSION: Sampling with ultrasound-guided FNA is of great value to improve the quality of FC specimens. FNA can significantly improve the sensitivity and accuracy of FC diagnosis in R/R DLBCL.

Leveraging Imitation Learning on Pose Regulation Problem of a Robotic Fish.

In this article, the pose regulation control problem of a robotic fish is investigated by formulating it as a Markov decision process (MDP). Such a typical task that requires the robot to arrive at the desired position with the desired orientation remains a challenge, since two objectives (position and orientation) may be conflicted during optimization. To handle the challenge, we adopt the sparse reward scheme, i.e., the robot will be rewarded if and only if it completes the pose regulation task. Although deep reinforcement learning (DRL) can achieve such an MDP with sparse rewards, the absence of immediate reward hinders the robot from efficient learning. To this end, we propose a novel imitation learning (IL) method that learns DRL-based policies from demonstrations with inverse reward shaping to overcome the challenge raised by extremely sparse rewards. Moreover, we design a demonstrator to generate various trajectory demonstrations based on one simple example from a nonexpert helper, which greatly reduces the time consumption of collecting robot samples. The simulation results evaluate the effectiveness of our proposed demonstrator and the state-of-the-art (SOTA) performance of our proposed IL method. Furthermore, we deploy the trained IL policy on a physical robotic fish to perform pose regulation in a swimming tank without/with external disturbances. The experimental results verify the effectiveness and robustness of our proposed methods in real world. Therefore, we believe this article is a step forward in the field of biomimetic underwater robot learning.

Mild Three-Step Consecutive C-H Activations.

Herein, the Rh-catalyzed consecutive C-H bond olefination/annulation/olefination cascade, tandemly directed by sulfonamide and ester groups, has been developed under mild conditions with the assistance of 1-adamantane carboxylic acid. A seven-membered metallacycle including an ester group was preferred to the five-membered one including a sulfonamide group for the third C-H activation. In this transformation, the Rh catalyst exhibits its high reactivity by catalyzing a triple C-H activation process with a low catalyst loading at 50 °C. This method can be applied in the construction of various pharmaceutical derivatives.

Pan-cancer analysis of ARID family members as novel biomarkers for immune checkpoint inhibitor therapy.

Although immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment, the accuracy of predictive biomarkers for ICI outcomes, such as PD-L1, TMB (tumor mutation burden) or MMR (mismatch repair) deficiency, have not been satisfactory. ARID family members are essential for maintaining the basic process of genomic stability and may serve as novel biomarkers for ICI therapy. A total of 1660 cancer patients who received ICI therapy were included in this pan-cancer analysis. The basic information and TMB values of each patient were collected. Survival analysis based on the Kaplan-Meier (KM) method was performed to explore the relationships between mutations in ARID family members and prognosis in pan-cancer as well as cancer subtypes. Genetic alterations in ARID1A (12%), ARID1B (5%), ARID2 (6%) and ARID5B (2.6%) were identified in multiple cancer types. Patients harboring mutated ARID family members benefited more from ICI therapy (P = .0003). Mutated ARID1A (P = .01), ARID1B (P = .0097) and ARID2 (P = .0054) all serve as compelling biomarkers in predicting the prognosis of ICI treatment. In addition, members of the ARID family were found to be strongly related to the abundance of CD4 + T cells and CD8 + T cells, the expression of PD-L1 and the TMB value in various cancers. Specifically, members of the ARID family could serve as novel biomarkers in multiple malignancies, especially gastrointestinal cancers. ARID family members serve as novel biomarkers for ICI therapy in malignancies. Testing the genomic status of ARID family members could help identify the definite subpopulation that benefits most from ICI treatment.Abbreviations: AT-rich interactive domain (ARID)Switch/sucrose nonfermenting (SWI/SNF)Non-small cell lung cancer (NSCLC)Immune checkpoint inhibitors (ICIs)Tumor microenvironment (TME)Programmed death-ligand 1 (PD-L1)Tumor mutational burden (TMB).

CPEB1 directs muscle stem cell activation by reprogramming the translational landscape.

Skeletal muscle stem cells, also called Satellite Cells (SCs), are actively maintained in quiescence but can activate quickly upon extrinsic stimuli. However, the mechanisms of how quiescent SCs (QSCs) activate swiftly remain elusive. Here, using a whole mouse perfusion fixation approach to obtain bona fide QSCs, we identify massive proteomic changes during the quiescence-to-activation transition in pathways such as chromatin maintenance, metabolism, transcription, and translation. Discordant correlation of transcriptomic and proteomic changes reveals potential translational regulation upon SC activation. Importantly, we show Cytoplasmic Polyadenylation Element Binding protein 1 (CPEB1), post-transcriptionally affects protein translation during SC activation by binding to the 3' UTRs of different transcripts. We demonstrate phosphorylation-dependent CPEB1 promoted Myod1 protein synthesis by binding to the cytoplasmic polyadenylation elements (CPEs) within its 3' UTRs to regulate SC activation and muscle regeneration. Our study characterizes CPEB1 as a key regulator to reprogram the translational landscape directing SC activation and subsequent proliferation.

Synthesis and photoluminescence enhancement of the LiLa(MoO4 )2 :Sm3+ red phosphors by co-doping with Bi3.

The LiLa(MoO4 )2 :Sm3+ and LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphors were prepared using the citric-acid-fueled combustion method and the influence of concentrations of Bi3+ dopant on LiLa(MoO4 )2 :Sm3+ red luminescence was investigated. The LiLa(MoO4 )2 :Sm3+ and LiLa(MoO4 )2 :Sm3+ ,Bi3+ samples matched well with the scheelite structure and I41 /a space group and did not detect structural changes. Under an excitation of 403 nm, the prepared LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphor was excited and produced orange-red emission. When compared with the LiLa(MoO4 )2 :Sm3+ phosphor, the LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphor exhibited enhanced fluorescence intensity because the Bi3+ dopant ions are doped as a sensitizer. The optimal doping concentrations of Sm3+ and Bi3+ were 5 and 1 mol%, respectively. Furthermore, the energy transfer from Bi3+ to Sm3+ is effective (3 P1 → 4 K11/2 ). Subsequently, the electrons in an unstable excited state were transferred to a stable ground state (4 G5/2 → 6 H5/2 , 6 H7/2 , 6 H9/2 ). The Commission Internationale de L'Eclairage (CIE) chromaticity coordinates of the optimized LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphor were situated in the orange-red region. The luminescence of the LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphor generated under near-ultraviolet (UV) irradiation could be used to produce a warm white light, indicating its possible applications in white light-emitting diodes.

LAG-3 is a promising inhibitory immune checkpoint for antitumor immunotherapy.

INTRODUCTION: Lymphocyte activation gene-3 (LAG-3) is a member of the immunoglobulin superfamily. Engagement of LAG-3 by its ligands to trigger downstream signaling can inhibit immune responses and regulate the pathogenesis of many diseases, including cancer and inflammatory diseases. AREAS COVERED: We used keywords to search for relevant publications in PubMed and information on websites. After systematic analysis, we discuss the biological characteristics of LAG-3 and its ligands, LAG-3 related signaling, its roles in the pathogenesis of tumors, and its blockages for the treatment of cancers, as well as current challenges and future directions of research. EXPERT OPINION: Although the mechanisms underlying the action of LAG-3/ligand-related signaling in tumor development are not fully understood, advances in scientific research and LAG-3-based immunotherapies are promising. Further studies to explore its biological roles and molecular mechanisms may aid in developing new LAG-3- and ligand-based therapeutic drugs to benefit patients with different types of cancers.

Association of TNFSF4 Gene Polymorphisms and Plasma TNFSF4 Level with Risk of Systemic Lupus Erythematosus in a Chinese Population.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease. Tumor necrosis factor ligand superfamily member 4 (TNFSF4) is an inflammatory factor that has been discussed in different inflammatory diseases and cancers. However, relationship between TNFSF4 and SLE is limited. MATERIAL AND METHODS: The present case-control study recruited 400 SLE patients and 600 healthy controls from Southern Chinese Han origin. Plasma levels of TNFSF4 were tested by enzyme linked-immunosorbent assay, and association of rs2205960, rs704840, rs844648, rs3850641 and rs17568 polymorphisms in TNFSF4 gene with SLE risk was evaluated by TaqMan assay according to genotyping. RESULTS: Plasma levels of TNFSF4 were significantly higher in SLE patients than that in healthy controls (390.87 (189.10-906.01) versus 132. 70 (81.27-195.58) pg/ml, P < 0.001). Increased levels of TNFSF4 were positively related to SLE disease activity score, optic nerve injury, leukopenia, and hypocompleminemia. Genotype TT+TG, allele T of rs2205960, genotype GG+GT of rs704840, genotype AA of rs844648 and rs17568 were significantly related to SLE risk (all P < 0.05). Moreover, polymorphism rs844648 was related to SLE patients with clinical feature rash either for genotype AA or allele A. CONCLUSION: TNFSF4 was elevated in SLE patients and may associate with SLE susceptibility in Southern Chinese Han population.

Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study.

BACKGROUND: Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line treatment in locally advanced or metastatic LSCC. METHODS: Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. RESULTS: The median duration of follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF-α, IFN-γ, IL-6, and IL-8, demonstrating an overlapping trend. CONCLUSION: The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

Similar pattern, different paths: tracing the biogeographical history of Megaloptera (Insecta: Neuropterida) using mitochondrial phylogenomics.

The sequential breakup of the supercontinent Pangaea since the Middle Jurassic is one of the crucial factors that has driven the biogeographical patterns of terrestrial biotas. Despite decades of effort searching for concordant patterns between diversification and continental fragmentation among taxonomic groups, increasing evidence has revealed more complex and idiosyncratic scenarios resulting from a mixture of vicariance, dispersal and extinction. Aquatic insects with discreet ecological requirements, low vagility and disjunct distributions represent a valuable model for testing biogeographical hypotheses by reconstructing their distribution patterns and temporal divergences. Insects of the order Megaloptera have exclusively aquatic larvae, their adults have low vagility, and the group has a highly disjunct geographical distribution. Here we present a comprehensive phylogeny of Megaloptera based on a large-scale mitochondrial genome sequencing of 99 species representing >90% of the world genera from all major biogeographical regions. Molecular dating suggests that the deep divergence within Megaloptera pre-dates the breakup of Pangaea. Subsequently, the intergeneric divergences within Corydalinae (dobsonflies), Chauliodinae (fishflies) and Sialidae (alderflies) might have been driven by both vicariance and dispersal correlated with the shifting continent during the Cretaceous, but with strikingly different and incongruent biogeographical signals. The austral distribution of many corydalids appears to be a result of colonization from Eurasia through southward dispersal across Europe and Africa during the Cretaceous, whereas a nearly contemporaneous dispersal via northward rafting of Gondwanan landmasses may account for the colonization of extant Eurasian alderflies from the south.