The Prognostic Value of CD39 as a Marker of Tumor-Specific T Cells in Triple-Negative Breast Cancer in Asian Women.

Triple-negative breast cancer (TNBC) has a poor prognosis with limited therapeutic options available for affected patients. Efforts are ongoing to identify surrogate markers for tumor-specific CD8+ T cells that can predict the response to immune checkpoint inhibitor (ICI) therapies, such as programmed cell death protein 1 or programmed cell death ligand-1 blockade. We have previously identified tumor-specific CD39+CD8+ T cells in non-small cell lung cancer that might help predict patient responses to programmed cell death protein 1 or programmed cell death ligand-1 blockade. Based on this finding, we conducted a comparative interrogation of TNBC in an Asian cohort to evaluate the potential of CD39 as a surrogate marker of tumor-specific CD8+ T cells. Using ICI-treated TNBC mouse models (n = 24), flow cytometric analyses of peripheral blood mononuclear cells and tumor-infiltrating lymphocytes revealed that >99% of tumor-specific CD8+ T cells also expressed CD39. To investigate the relationship between CD39+CD8+ T-cell density and CD39 expression with disease prognosis, we performed multiplex immunohistochemistry staining on treatment-naive human TNBC tissues (n = 315). We saw that the proportion of CD39+CD8+ T cells in human TNBC tumors correlated with improved overall survival, as did the densities of other CD39+ immune cell infiltrates, such as CD39+CD68+ macrophages. Finally, increased CD39 expression on CD8+ T cells was also found to predict the response to ICI therapy (pembrolizumab) in a separate cohort of 11 TNBC patients. These findings support the potential of CD39+CD8+ T-cell density as a prognostic factor in Asian TNBC patients.

A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma trials group (NCT03267641), we recruited one of the largest prospective cohorts of patients with HCC, with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provides a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected hepatocellular carcinoma (HCC), reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of HCC. These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for personalized treatment strategies tailored to specific tumor evolutionary and transcriptomic profiles. The coexistence of multiple subtypes within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort).

Highly Stable Lithium Metal Batteries Enabled by Tuning the Molecular Polarity of Diluents in Localized High-Concentration Electrolytes.

Electrolyte plays a crucial role in ensuring stable operation of lithium metal batteries (LMBs). Localized high-concentration electrolytes (LHCEs) have the potential to form a robust solid-electrolyte interphase (SEI) and mitigate Li dendrite growth, making them a highly promising electrolyte option. However, the principles governing the selection of diluents, a crucial component in LHCE, have not been clearly determined, hampering the advancement of such a type of electrolyte systems. Herein, the diluents from the perspective of molecular polarity are rationally designed and developed. A moderately fluorinated solvent, 1-(1,1,2,2-tetrafluoroethoxy)propane (TNE), is employed as a diluent to create a novel LHCE. The unique molecular structure of TNE enhances the intrinsic dipole moment, thereby altering solvent interactions and the coordination environment of Li-ions in LHCE. The achieved solvation structure not only enhances the bulk properties of LHCE, but also facilitates the formation of more stable anion-derived SEIs featured with a higher proportion of inorganic species. Consequently, the corresponding full cells of both Li||LiFePO4 and Li||LiNi0.8Co0.1Mn0.1O2 cells utilizing Li thin-film anodes exhibit extended long-term stability with significantly improved average Coulombic efficiency. This work offers new insights into the functions of diluents in LHCEs and provides direction for further optimizing the LHCEs for LMBs.

Umpolung Flow Chemistry for the Synthesis of a 3-Oxo-3H-spiro[benzofuran-2,4'-piperidine] Building Block.

An efficient and scalable route to tert-butyl 3-oxo-3H-spiro[benzofuran-2,4'-piperidine]-1'-carboxylate, a central prochiral intermediate in the synthesis of SHP2 inhibitor GDC-1971 (migoprotafib), was achieved. Preparation of the title compound from readily available 2-fluorobenzaldehyde included formation of a modified Katritzky benzotriazole hemiaminal, which, upon deprotonation by n-butyllithium, participated in umpolung reactivity via 1,2-addition to tert-butyl 4-oxopiperidine-1-carboxylate (N-Boc-4-piperidone). Most notably, this reaction was developed as a robust plug-flow process that could be executed on multiple kilograms without the need for pilot-scale reaction vessels operating at low cryogenic temperatures. Treatment of the resulting tetrahedral intermediate with oxalic acid resulted in collapse to the corresponding 4-(2-fluorobenzoyl)-4-hydroxypiperidine, which was isolated as a solid via crystallization. The synthesis concluded with an optimized intramolecular SNAr reaction and final crystallization to generate tert-butyl 3-oxo-3H-spiro[benzofuran-2,4'-piperidine]-1'-carboxylate as a stable, high-quality intermediate suitable for further functionalization toward GDC-1971.

Important yet Overlooked HONO Source from Aqueous-phase Photochemical Oxidation of Nitrophenols.

Nitrites (NO2-/HONO), as the primary source of hydroxyl radicals (•OH) in the atmosphere, play a key role in atmospheric chemistry. However, the current understanding of the source of NO2-/HONO is insufficient and therefore hinders the accurate quantification of atmospheric oxidation capacity. Herein, we highlighted an overlooked HONO source by the reaction between nitrophenols (NPs) and •OH in the aqueous phase and provided kinetic data to better evaluate the contribution of this process to atmospheric HONO. Three typical NPs, including 4-nitrophenol (4NP), 2-nitrophenol (2NP), and 4-nitrocatechol (4NC), underwent a denitration process to form aqueous NO2- and gaseous HONO through the •OH oxidation, with the yield of NO2-/HONO varied from 15.0 to 33.5%. According to chemical composition and structure analysis, the reaction pathway, where the ipso addition of •OH to the NO2 group on 4NP generated hydroquinone, can contribute to more than 61.9% of the NO2-/HONO formation. The aqueous photooxidation of NPs may account for HONO in the atmosphere, depending on the specific conditions. The results clearly suggest that the photooxidation of NPs should be considered in the field observation and calculation to better evaluate the HONO budget in the atmosphere.

Millimeter-Wave Radar-Based Identity Recognition Algorithm Built on Multimodal Fusion.

Millimeter-wave radar-based identification technology has a wide range of applications in persistent identity verification, covering areas such as security production, healthcare, and personalized smart consumption systems. It has received extensive attention from the academic community due to its advantages of being non-invasive, environmentally insensitive and privacy-preserving. Existing identification algorithms mainly rely on a single signal, such as breathing or heartbeat. The reliability and accuracy of these algorithms are limited due to the high similarity of breathing patterns and the low signal-to-noise ratio of heartbeat signals. To address the above issues, this paper proposes an algorithm for multimodal fusion for identity recognition. This algorithm extracts and fuses features derived from phase signals, respiratory signals, and heartbeat signals for identity recognition purposes. The spatial features of signals with different modes are first extracted by the residual network (ResNet), after which these features are fused with a spatial-channel attention fusion module. On this basis, the temporal features are further extracted with a time series-based self-attention mechanism. Finally, the feature vectors of the user's vital sign modality are obtained to perform identity recognition. This method makes full use of the correlation and complementarity between different modal signals to improve the accuracy and reliability of identification. Simulation experiments show that the algorithm identity recognition proposed in this paper achieves an accuracy of 94.26% on a 20-subject self-test dataset, which is much higher than that of the traditional algorithm, which is about 85%.

Wideband Terminal Antenna System Based on Babinet's Principle for Sub-6 GHz and Wi-Fi 6E/7 Applications.

In this paper, a novel input impedance analysis methodology based on Babinet's principle to broaden bandwidth is proposed, and a broadband multiple-input and multiple-output (MIMO) antenna system is designed, fabricated, and measured for fifth-generation (5G) and Wireless Fidelity (Wi-Fi) 6E/7 mobile applications. By analyzing the input impedance of open-slot antennas and planar monopole antennas using numerical calculations, the characteristics of the input impedance can be obtained. We find that combining the two antenna types in parallel can significantly enhance the bandwidth. Then, the four-dimensional image calculated by MATLAB based on the parallel impedance formula is processed to validate the methodology. Thus, a broad antenna element based on the impedance property analysis methodology is achieved, which operates ranging from 2.6 GHz to 7.46 GHz. Moreover, the equivalent circuit of the antenna element is established to further verify the validity of the methodology. Finally, a broadband MIMO antenna system consisting of eight antenna elements is designed, fabricated, and measured, and the isolation performance is better than 12 dB. Acceptable total efficiency higher than 45% is also obtained with envelope correlation coefficients (ECCs) lower than 0.05. The proposed impedance property analysis methodology innovatively proposes a new way to increase bandwidth, which can be widely applied in various antenna designs. Also, reasonable results show that the proposed MIMO antenna system is a good candidate for 5G and Wi-Fi 6E/7 mobile applications.

Autumn and spring observations of PM2.5-bound polycyclic aromatic hydrocarbons and nitro-polycyclic aromatic hydrocarbons in China and Japan.

The transboundary transport of polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs (NPAHs) aggravated by the East Asian winter monsoon is a major atmospheric environmental issue in East Asia. To thoroughly elucidate the role of the East Asian monsoon on regional PAH and NPAH pollution in East Asia, PM2.5-bound PAHs and NPAHs were investigated concurrently at five sites in Beijing and Shenyang in China and Tsukuba, Kanazawa, and Wajima in Japan in autumn (November 2018) and spring (March 2019). During both autumn and spring sampling periods, the concentrations of PM2.5, PAHs, and NPAHs at sites in China were 1-2 orders of magnitude higher than those at sites in Japan, and showed an opposite temporal variation, with higher concentrations during the autumn sampling period due to intensive emissions and unfavourable weather conditions. During the sampling periods, PAHs at the Beijing and Shenyang sites had mixed sources of traffic emissions and coal and biomass combustion, while those at the Tsukuba, Kanazawa, and Wajima sites were mainly characterized by domestic traffic emissions. In addition, NPAHs at the five sites were jointly affected by primary combustion sources and atmospheric generation, with a greater contribution of atmospheric generation to the Beijing and Shenyang sites. Based on backwards trajectory clustering and concentration-weighted trajectory analysis, external contributions to PM2.5, PAHs, and NPAHs at each site were relatively stable during the two sampling periods, and potential source areas were mainly distributed in domestic cities and nearby sea areas. Therefore, the apparent temporal differences in the characteristics and sources of pollutants between sites in the two countries indicate that transboundary pollution dominated by the East Asian winter monsoon was unobvious in autumn and spring. The results of the study provide a time-specific solution for the effective management of regional air pollution during the East Asian winter monsoon.

Reactive oxygen species play key roles in the nitrite formation by the inorganic nitrate photolysis in the presence of urban water-soluble organic carbon.

Inorganic nitrates were considered to be a potential source of atmospheric NO2-/HONO during the daytime. To better evaluate the contribution of nitrate photochemistry on NO2-/HONO formation, the photolysis of nitrates in the real atmospheric environment needs to be further explored. Here, the NO2- generation by the photolysis of inorganic nitrates in the presence of total water-soluble organic carbon (WSOC) was quantified. The physicochemical properties of WSOC were measured to understand the underlying mechanism for the photolysis of inorganic nitrates with WSOC. WSOC enhanced or suppressed the photochemical conversion of nitrates to NO2-, with the quantum yield of NO2- (ΦNO2-) varying from (0.07 ± 0.02)% to (3.11 ± 0.04)% that depended on the light absorption properties of WSOC. Reactive oxygen species (ROS) generated from WSOC, including O2-/HO2 and OH, played a dual role in the NO2- formation. Light-absorbing substances in WSOC, such as N-containing and carbonyl aromatics, produced O2-/HO2 that enhanced the secondary conversion of NO2 to NO2-. On the other hand, OH deriving from the WSOC photochemistry inhibited the nitrate photodegradation and the NO2- formation. HONO source strength by the aqueous photolysis of nitrates with WSOC was estimated to be lower than 100 ppt h-1, which may partly contribute to the atmospheric HONO source in some cases.

Pneumonitis Risk After Chemoradiotherapy With and Without Immunotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Chemoradiotherapy (CRT) combined with immune checkpoint inhibitors (ICIs) is the standard of care for patients with unresectable and locally advanced non-small cell lung cancer. This study aimed to determine whether the addition of ICIs to CRT is associated with an increased risk of pneumonitis. METHODS AND MATERIALS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies published between January 1, 2015, and July 31, 2023. The outcome of interest was the incidence rate of pneumonitis. A random-effects model was used for statistical analysis. RESULTS: A total of 185 studies with 24,527 patients were included. The pooled rate of grade ≥2 pneumonitis for CRT plus ICIs was significantly higher than that for CRT alone (29.6%; 95% CI, 25.7%-33.6% vs 20.2%; 95% CI, 17.7%-22.8%; P < .0001) but not that of grade ≥3 (5.7%; 95% CI, 4.8%-6.6% vs 5.6%; 95% CI, 4.7%-6.5%; P = .64) or grade 5 (0.1%; 95% CI, 0.0%-0.2% vs 0.3%; 95% CI, 0.1%-0.4%; P = .68). The results from the subgroup analyses of prospective studies, retrospective studies, Asian and non-Asian studies, concurrent CRT (cCRT), and durvalumab consolidation were comparable to the overall results. However, CRT or cCRT plus PD-1 inhibitors not only significantly increased the incidence of grade ≥2 but also that of grade ≥3 pneumonitis compared to CRT alone or cCRT plus PD-L1 inhibitors. CONCLUSIONS: Compared with CRT alone, durvalumab consolidation after CRT appears to be associated with a higher incidence of moderate pneumonitis and CRT plus PD-1 inhibitors with an increased risk of severe pneumonitis. Nevertheless, these findings are based on observational studies and need to be validated in future large head-to-head studies.

Network pharmacology and molecular-docking-based strategy to explore the potential mechanism of salidroside-inhibited oxidative stress in retinal ganglion cell.

BACKGROUND: Salidroside (SAL), the main component of Rhodiola rosea extract, is a flavonoid with biological activities, such as antioxidative stress, anti-inflammatory, and hypolipidemic. In this study, the potential therapeutic targets and mechanisms of SAL against oxidative stress in retinal ganglion cells (RGCs) were investigated on the basis of in-vitro experiments, network pharmacology, and molecular docking techniques. METHODS: RGC oxidative stress models were constructed, and cell activity, reactive oxygen species (ROS), and apoptosis levels were examined for differences. The genes corresponding to rhodopsin, RGCs, and oxidative stress were screened from GeneCards, TCMSP database, and an analysis platform. The intersection of the three was taken, and a Venn diagram was drawn. Protein interactions, GO functional enrichment, and KEGG pathway enrichment data were analyzed by STRING database, Cytohubba plugin, and Metascape database. The key factors in the screening pathway were validated using qRT-PCR. Finally, molecular docking prediction was performed using MOE 2019 software, molecular dynamic simulations was performed using Gromacs 2018 software. RESULTS: In the RGC oxidative stress model in vitro, the cell activity was enhanced, ROS was reduced, and apoptosis was decreased after SAL treatment. A total of 16 potential targets of oxidative stress in SAL RGCs were obtained, and the top 10 core targets were screened by network topology analysis. GO analysis showed that SAL retinal oxidative stress treatment mainly involved cellular response to stress, transcriptional regulatory complexes, and DNA-binding transcription factor binding. KEGG analysis showed that most genes were mainly enriched in multiple cancer pathways and signaling pathways in diabetic complications, nonalcoholic fatty liver, and lipid and atherosclerosis. Validation by PCR, molecular docking and molecular dynamic simulations revealed that SAL may attenuate oxidative stress and reduce apoptosis in RGCs by regulating SIRT1, NRF2, and NOS3. CONCLUSION: This study initially revealed the antioxidant therapeutic effects and molecular mechanisms of SAL on RGCs, providing a theoretical basis for subsequent studies.

Multiple Tissues Transcriptome of Zig-Zag Eel (Mastacembelus armatus) with Different Growth Rates.

In order to explore the main regulatory genes and related pathways of growth traits, transcriptome sequencing was first performed on the brain, liver, and muscle tissues of 3-month-old M. armatus with different growth rates. By comparative transcriptome analysis of fast-growing and slow-growing groups of M. armatus, a total of 2887 DEGs were screened, of which 59 up-regulated genes and 105 down-regulated genes were detected in the brain, 146 up-regulated genes and 202 down-regulated genes were detected in the liver, and 529 up-regulated genes and 1846 down-regulated genes were detected in muscle, including insulin-like growth factor binding protein 1a (IGFBP1A), insulin-like growth factor binding protein 1b (IGFBP1B), myosin, light chain 1 (MYL1), and myoglobin (MB). Through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we identified a total of 288 significantly enriched GO entries and 68 significantly enriched KEGG pathways related to growth, such as skeletal muscle tissue development, insulin-like growth factor binding, and the mitotic cell cycle. These key genes and signaling pathways may play a key role in regulating the growth of M. armatus. Digging into the regulatory mechanisms of these key genes will provide a theoretical basis for further exploration of the molecular mechanisms related to the growth and development of M. armatus, and help to breed new varieties of M. armatus with rapid growth.

De Novo Assembly, Characterization, and Comparative Transcriptome Analysis of Mature Male and Female Gonads of Rabbitfish (Siganus oramin) (Bloch & Schneider, 1801).

The rabbitfish, Siganus oramin, is a commercially important table fish in southeastern China. However, there have been few studies on its gonad development and reproduction regulation. Comparative transcriptome analysis was first performed on adult male and female gonads of S. oramin. In total, 47,070 unigenes were successfully assembled and 22,737 unigenes were successfully annotated. Through comparative transcriptome analysis of male and female gonads, a total of 6722 differentially expressed genes were successfully identified, with 3528 upregulated genes and 3154 downregulated genes in the testes. In addition, 39 differentially expressed reproduction-related genes were identified. Finally, quantitative real-time PCR was used to validate the expression levels of several differentially expressed genes. These results provide important data for further studying the function of reproduction-related genes and the molecular mechanism regulating gonad development and reproduction in S. oramin.

No genetic causal association between periodontitis and ankylosing spondylitis: a bidirectional two-sample mendelian randomization analysis.

BACKGROUND: Observational studies that reveal an association between periodontitis (PD) and ankylosing spondylitis (AS) exist. However, observational research is prone to reverse causality and confounding factors, which make it challenging to infer cause-and-effect relationships. We conducted a two-sample Mendelian randomization (MR) study to examine the causal relationship between the genetic prediction of PD and AS. METHODS: In our study, single-nucleotide polymorphisms (SNPs) were defined as instrumental variables (IVs). The genetic association with PD came from the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) consortium, wherein 17353 cases of European ancestry and 28210 controls of European ancestry were included in this study. The genetic association with AS from the Neale Laboratory Consortium included 337,159 individuals from the United Kingdom, with 968 cases and 336,191 controls. MR analysis was mainly performed using the inverse-variance weighted (IVW) method. In addition, the robustness of the study findings was assessed using sensitivity, pleiotropy, and heterogeneity analyses. RESULTS: Eighteen independent SNPs with P-values significantly smaller than 1 × 10- 5 were used as IV SNPs for PD, while 39 independent SNPs with P-values significantly smaller than 1 × 10- 5 were used as IV SNPs for AS. The results of the IVW method revealed no causal association between PD and AS (odds ratio = 1.00, 95% confidence interval: 0.99953 to 1.00067, P = 0.72). The MR-Egger method did not support the causal association between PD and AS. It is unlikely that horizontal pleiotropy distorts causal estimates based on sensitivity analysis. No significant heterogeneity was observed in the Q test. The ''leave-one-out'' analysis demonstrated that the robustness of our results was unaffected by eliminating any of the IVs. Likewise, no significant causative effect for AS on PD was observed in the inverse MR analysis. CONCLUSIONS: The study results do not support shared heritability or a causal association between PD and AS.

A novel approach to managing facility airborne diseases: suppressing air pathogens with smoke aerosols generated from fungicide phase transition.

BACKGROUND: Environmental microorganisms are major contributors to the development and spread of disease. Chemical disinfection can inhibit pathogens and play a preventive role against diseases. In agriculture, prolonging the floating time of chemical pesticides in the air has a positive effect on the control of airborne diseases. However, the interaction of chemical pesticides with airborne pathogens is not yet known. RESULTS: Here, triazole fungicide was transformed into stable smoke aerosols in order to assess the feasibility of employing phase transition release pesticides for air disinfection. The phase transition had a minimal impact on hexaconazole (Hexa) and myclobutanil (Mycl), with their smoke formation rates remaining consistently >90%. In microscopic morphology, triadimenol (Tria) and epoxiconazole (Epox) are solid, and tebuconazole (Tebu), Hexa, Mycl and difenoconazole (Dife) are liquid. Liquid smoke has advantages over solid smoke in the inhibition of environmental pathogens. The floatability and spatial distribution of fungicide aerosol were optimized by the combination of smoke particles with different properties, so that the fungicide aerosol could meet the conditions of practical application. In practical applications, smoke exhibits a gentler deposition process at the target interface compared to spray, along with a more homogeneous distribution of fungicides. Moreover, fungicide smoke demonstrates superior control efficacy and leaves behind lower residual amounts on fruit. CONCLUSION: In conclusion, the implementation of fungicide phase transition as a smoke aerosol offers a viable approach to effectively suppress pathogen aerosols and enhance the control of airborne diseases. © 2024 Society of Chemical Industry.

Sex differences in cancer and immunotherapy outcomes: the role of androgen receptor.

Across the wide range of clinical conditions, there exists a sex imbalance where biological females are more prone to autoimmune diseases and males to some cancers. These discrepancies are the combinatory consequence of lifestyle and environmental factors such as smoking, alcohol consumption, obesity, and oncogenic viruses, as well as other intrinsic biological traits including sex chromosomes and sex hormones. While the emergence of immuno-oncology (I/O) has revolutionised cancer care, the efficacy across multiple cancers may be limited because of a complex, dynamic interplay between the tumour and its microenvironment (TME). Indeed, sex and gender can also influence the varying effectiveness of I/O. Androgen receptor (AR) plays an important role in tumorigenesis and in shaping the TME. Here, we lay out the epidemiological context of sex disparity in cancer and then review the current literature on how AR signalling contributes to such observation via altered tumour development and immunology. We offer insights into AR-mediated immunosuppressive mechanisms, with the hope of translating preclinical and clinical evidence in gender oncology into improved outcomes in personalised, I/O-based cancer care.

Lignin microcapsules prepared on the basis of flexible skeleton with high foliar retention and UV shielding properties.

Lignin-based microcapsules are extremely attractive for their biodegradability and photolysis resistance. However, the water-soluble all-lignin shells were unsatisfactory in terms of rainfall and foliar retention, and lacked the test of agricultural production practices. Herein, a novel microcapsule based on a flexible skeleton formed by interfacial polymerization and absorbed with lignin particles (LPMCs) was prepared in this study. Further analysis demonstrated that the shell was formed by cross-linking the two materials in layers and showed excellent flexibility and photolysis resistance. The pesticide loaded LPMCs showed about 98.68 % and 73.00 % improvement in scour resistance and photolysis resistance, respectively, as compared to the bare active ingredient. The foliar retention performance of LPMCs was tested in peanut plantations during the rainy season. LPMCs loaded with pyraclostrobin (Pyr) and tebuconazole (Teb) exhibited the best foliar disease control and optimum plant architecture, resulting in an increase in yield of about 5.36 %. LPMCs have a promising application prospect in the efficient pesticide utilization, by controlling its deformation, adhesion and release, an effective strategy for controlling diseases and managing plant growth was developed.

Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for ~90% of liver neoplasms. It is the second leading cause of cancer-related deaths and the seventh most common cancer worldwide. Although there have been rapid developments in the treatment of HCC over the past decade, the incidence and mortality rates of HCC remain a challenge. With the widespread use of the hepatitis B vaccine and antiviral therapy, the etiology of HCC is shifting more toward metabolic-associated steatohepatitis (MASH). Early-stage HCC can be treated with potentially curative strategies such as surgical resection, liver transplantation, and radiofrequency ablation, improving long-term survival. However, most HCC patients, when diagnosed, are already in the intermediate or advanced stages. Molecular targeted therapy, followed by immune checkpoint inhibitor immunotherapy, has been a revolution in HCC systemic treatment. Systemic treatment of HCC especially for patients with compromised liver function is still a challenge due to a significant resistance to immune checkpoint blockade, tumor heterogeneity, lack of oncogenic addiction, and lack of effective predictive and therapeutic biomarkers.

Efficacy and Safety of Cell-based Immunotherapy in The Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma - A Systematic Review and Meta-analysis.

BACKGROUND: Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias. RESULTS: We screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %-29 %), median PFS of 2.37 months (95 %CI = 1.23-3.51) and median OS of 10.16 months (95 %CI = 0.67-19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %-93 %), SD rate was 22 % (95 %CI = 2 %-75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %-98 %), SD rate of 11 % (95 % CI = 0 %-82 %) and incidence rate of any grade adverse events of 29 % was achieved. CONCLUSION: CBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.

Cost-effectiveness analysis of atezolizumab plus bevacizumab compared with sorafenib as first-line treatment in advanced hepatocellular carcinoma in Singapore.

OBJECTIVES: This study aims to explore the cost-effectiveness of atezolizumab plus bevacizumab against sorafenib for first-line treatment of locally advanced or metastatic hepatocellular carcinoma (HCC) in Singapore. METHODS: A partitioned survival model was developed from a healthcare system perspective, with a 10-year lifetime horizon. Clinical inputs and utilities were obtained from the IMbrave150 trial. Healthcare resource use costs were obtained from published local sources; drug costs reflected the most recent public hospital selling prices. Outcomes included life years, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to assess the model's robustness. RESULTS: Atezolizumab plus bevacizumab offered an additional 1.42 life years and 1.09 QALYs, with an additional cost of S$111,847; the ICER was S$102,988/QALY. The World Health Organization considers interventions with ICERs <1 gross domestic product (GDP)/capita to be highly cost-effective. At a willingness-to-pay (WTP) threshold of S$114,165/QALY (Singapore's 2022 GDP/capita), atezolizumab plus bevacizumab is cost-effective compared with sorafenib. The ICER was most sensitive to variations in utilities, but all parameter variations had no significant impact on the model outcomes. CONCLUSION: At a WTP threshold of Singapore's GDP/capita, atezolizumab plus bevacizumab is cost-effective compared with sorafenib.