Ovarian cancer is the most lethal gynecologic malignancy. Surgery and chemotherapy are the primary treatments for ovarian cancer; however, patients often succumb to recurrence with chemotherapeutic ...resistance within several years after the initial treatment. In the past two decades, immunotherapy has rapidly developed, and has revolutionized the treatment of various types of cancer. Despite the fact that immunotherapy response rates among ovarian cancer patients remain modest, treatment with immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)- and TCR-engineered T cells is rapidly developing. Therapeutic efficiency could be improved significantly if immunotherapy is included as an adjuvant therapy, in combination with chemotherapy, radiation therapy, and the use of anti-angiogenesis drugs, and poly ADP ribose polymerase inhibitors (PARPi). Newly developed technologies that identify therapeutic targets, predict treatment efficacy, rapidly screen potential immunotherapy drugs, provide neoadjuvant immunotherapy, and utilize nanomedicine technology provide new opportunities for the treatment of ovarian cancer, and have the potential to prolong patient survival. However, important issues that may hinder the efficacy of such approaches, including hyperprogressive disease (HPD), immunotherapy-resistance, and toxicity of the treatments, including neurotoxicity, must be taken into account and addressed for these therapies to be effective.
Here, π-Extended BTD derivatives were successfully synthesized by Heck coupling reaction, which exhibited the the advantages of simplicity and efficiency, wild substrate scope, easily available ...substrates and high yield. The fluorescent probe PEG-BTDAr targeting LDs was successfully prepared by the nucleophilic substitution reaction between the Heck coupling reaction product 3 h and Amino polyethylene glycol monomethyl ether (Mn=2000). PEG-BTDAr exhibited the advantages of high selectivity, good stability and pH resistance. The use of PEG as a substrate gave PEG-BTDAr good biocompatibility. It was worth mentioning that PEG-BTDAr could not only track LDs in cells under different physiological conditions, but also distinguish between living and dead cells in biological systems.
Background: Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth ...most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. Summary: This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. Key Messages: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.
The aim of this study was to develop a model for early prediction of adverse events and treatment effectiveness in patients with hyperkalemia. We collected clinical data from patients with ...hyperkalemia in the First Hospital of Zhejiang University School of Medicine between 2015 and 2021. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to analyze the predictors on the full dataset. We randomly divided the data into a training group and a validation group, and used LASSO to filter variables in the training set. Six machine learning methods were used to develop the models. The best model was selected based on the area under the curve (AUC). Shapley additive exPlanations (SHAP) values were used to explain the best model. A total of 1074 patients with hyperkalemia were finally enrolled. Diastolic blood pressure (DBP), breathing, oxygen saturation (SPO2), Glasgow coma score (GCS), liver disease, oliguria, blood sodium, international standardized ratio (ISR), and initial blood potassium were the predictors of the occurrence of adverse events; peripheral edema, estimated glomerular filtration rate (eGFR), blood sodium, actual base residual, and initial blood potassium were the predictors of therapeutic effect. Extreme gradient boosting (XGBoost) model achieved the best performance (adverse events: AUC = 0.87; therapeutic effect: AUC = 0.75). A model based on clinical characteristics was developed and validated with good performance.
Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. ...Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.
Solid-state lithium batteries require the high energy density, easy processing and flexibility of electrolyte membranes. However, the low-temperature ionic conductivity and high interfacial impedance ...are still hindering the further application. Therefore, we developed the solution pouring method by using lithium bis(oxalate)borate (LiBOB) to prepare the PEO/LiBOB/LLZTO solid electrolyte for room-temperature solid-state lithium battery. Compared with the traditional LiPF
6
as a lithium additive, the solid-state electrolytes with LiBOB as additive hold higher ionic conductivity and electrochemical window. Moreover, the fabricated solid-state LiFePO
4
|Li batteries own higher specific capacity and excellent cycle performance at room temperature (165.9 mAh g
−1
with capacity retention of 84.6% after 100 cycles). The large volume of LiBOB could effectively decrease the crystallization state of PEO to improve the conductivity of Li
+
ion by the increase in the amorphous region in the whole polymer electrolyte system. This study offers a feasible strategy of preparing solid electrolytes for room-temperature solid-state lithium battery with high performance.
Lipid droplets (LDs) and lysosomes serve as important subcellular organelles, which plays an important role in a variety of physiological processes. The components in lipid droplets can be degraded ...by lysosomes, so it is of great value to study the relationship between LDs and lysosomes. However, simultaneous targeting of lipid droplets and lysosomal polymer fluorescent probes has hardly been reported. Therefore, we developed a novel polyethylene glycol fluorescent probe PEG-Nap-Lyso that could be applied to simultaneously track lysosomes and lipid droplets. PEG-Nap-Lyso was able to not only track cells in different physiological environments, but also differentiate live cells from dead cells by changes in the polarity of the intracellular microenvironment. In addition, the probe had the advantages of amphiphilicity, pH resistance, high selectivity, good stability (3600s), low biotoxicity and large Stokes shift (167 nm). These excellent properties made the fluorescent probe PEG-Nap-Lyso provided an effective way to study the relationship between LDs and lysosomes.
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•A unique amphipathic PEG-based fluorescent probe PEG-Nap-Lyso was designed with a large Stokes shift (167 nm).•The novel fluorescent probe could target lipid droplets and lysosomes in living cells.•The novel fluorescent probe had been successfully used for dual-channel imaging to discriminate living and dead cells.•The novel fluorescent probe could tracking LDs in cells under different physiological conditions.
Lipid droplets (LDs) and lysosomes serve as important subcellular organelles, which plays an important role in a variety of physiological processes. The components in lipid droplets can be degraded by lysosomes, so it is of great value to study the relationship between LDs and lysosomes. However, few polymer fluorescent probes targeting both lipid droplets and lysosomes have been reported. Therefore, we developed a novel polyethylene glycol fluorescent probe PEG-Nap-Lyso that could be applied to simultaneously track lysosomes and lipid droplets. PEG-Nap-Lyso was able to not only track cells in different physiological environments, but also differentiate live cells from dead cells by changes in the polarity of the intracellular microenvironment. In addition, the probe showed the advantages of amphiphilicity, pH resistance, high selectivity, good stability (3600 s), low biotoxicity and large Stokes shift (167 nm). These excellent properties made the fluorescent probe PEG-Nap-Lyso provided an effective way to study the relationship between LDs and lysosomes.
Changes in soil nutrients variability could significantly interact with other global change processes (such as community dynamics, biological invasion). Global exchange and accumulation of alien ...species caused environmental and economic threats in the introduced ranges. Their invasion success or not in local plant communities is largely depended on the interactions and competitive outcomes with other species and environmental conditions. Here, we tested whether the interactions of nutrient variability and competitor identity influence plant performance, potential invasion success of invasive species and their co-existence with native species. In both greenhouse and field experiment, we subjected three congeneric and naturally co-occurring pairs of invasive alien and native clonal plants in China to different nutrient variability (constant high, multiple pulses and/or single pulse) and competitor identity (intra-specific competitors, native competitors, invasive competitors and both native & invasive competitors). Our results showed that total biomass or the increase of cover of invasive species was significantly larger than those of the native species regardless of competitor identity. Native competitors significantly decreased biomass proportion of native species, but did not affect that of invasive species. The whole community with invasive target species accumulated more total biomass than with native species under multiple pulses nutrient when with the native competitors. Invasive species produced significantly higher biomass proportion than natives under all competitor identity treatments except for native & invasive competitors. Multiple mixed competitors (i.e. native & invasive competitors) decreased the plant performance and dominance of invasive target species, to some extent, thus construction of multi-species competition might facilitate coexistence of native and invasive species in communities. Interactions between native competitors or native & invasive competitors, and nutrient variability play important roles in plant performance and potential invasion success in communities. Multiple invasional interference may have significant implications for the co-existence of invasive and native species, and for management of invasive species.
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•Total biomass and increase of cover of invasive species was larger than native.•Native competitors decreased biomass proportion of native species.•The invasive community accumulated more biomass under multiple pulses nutrient.•Invasive species produced significantly higher biomass proportion than natives.•Multiple invasional interference have significant implications for the co-existence.
Background and aims
Heavy metal (especially for potentially toxic element) contamination in soil has frequently been associated with plant invasion. However, the mechanisms underpinning plant ...invasion under potentially toxic element contamination remain unclear. Here we studied how differences in clonal traits of invasive and native plants affect their response strategies to stresses of potentially toxic element contamination.
Methods
We manipulated clonal integration of two pairs (
Alternanthera philoxeroides - A. sessilis
, and
Sphagneticola trilobata
-
S. calendulacea
) of congeneric invasive and native plants by either severing stolons between ramet pair or not severing, and grew them in soils contaminated by three levels of Cd and three levels of Pb.
Results
Our results show that the combination of Cd and Pb contamination decreased plant growth of recipient ramets of
Alternanthera
species. Under Pb stress, invasive
S. trilobata
is Pb-hyperaccumulation and benefits more from clonal integration than native
S. calendulacea
. Similarly, under Cd stress, invasive
A. philoxeroides
shows higher Cd risk sharing and benefits more from clonal integration than native
A. sessilis.
In contrast, clonal integration decreased the performance of
A. sessilis
under high Cd stress.
Conclusion
These results suggest that invasive species such as
A. philoxeroides and S. trilobata
are able to alleviate the toxic effects of Cd and Pb co-contamination via clonal integration, thus becoming more invasive in contaminated environments with potentially toxic elements.
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