Cellulose Nanofiber-Based Triboelectric Nanogenerators for Efficient Air Filtration in Harsh Environments.

Advanced portable healthcare devices with high efficiencies, small pressure drops, and high-temperature resistance are urgently desired in harsh environments with high temperatures, high humidities, and high levels of atmospheric pollution. Triboelectric nanogenerators (TENGs), which serve as energy converters in a revolutionary self-powered sensor device, present a sustainable solution for meeting these requirements. In this work, we developed a porous negative triboelectric material by synthesizing ZIF-8 on the surface of a cellulose/graphene oxide aerogel, grafting it with trimethoxy(1H,1H,2H,2H-heptadecafluorodecyl)silane, and adding a negative corona treatment, and it was combined with a positive triboelectric material to create a cellulose nanofiber-based TENG self-powered filter. The devices achieved a balance between a small pressure drop (53 Pa) and high filtration efficiency (98.97%, 99.65%, and 99.93% for PM0.3, PM0.5, and PM1, respectively), demonstrating robust filtration properties at high temperatures and high humidities. Our work provides a new approach for developing self-powered wearable healthcare devices with excellent air filtration properties.

Zwitterionic Injectable Hydrogel-Combined Chemo- and Immunotherapy Medicated by Monomolecular Micelles to Effectively Prevent the Recurrence of Tumor Post Operation.

Surgical resection remains the most common method of tumor treatment; however, the high recurrence and metastasis after surgery need to be solved urgently. Herein, we report an injectable zwitterionic hydrogel based on "thiol-ene" click chemistry containing doxorubicin (DOX) and a macrophage membrane (MM)-coated 1-methyl-tryptophan (1-MT)-loaded polyamide-amine dendrimer (P-DOX/1MT) for preventing the postoperative recurrence of tumors. The results indicated that P-DOX/1MT@MM exhibited enhanced recognition and uptake of the dendrimer by tumor cells and induced the immunogenic cell death. In the mice tumor model, the P-DOX/1MT@MM-Gel exhibited high therapeutic efficiency, which could significantly reduce the recurrence of the tumor, including suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. The mechanism analysis revealed that the hydrogel greatly reduces the side effects to normal tissues and significantly improves its therapeutic effect. 1MT in the hydrogel is released more rapidly, improving the tumor suppressor microenvironment and increasing the tumor cell sensitivity to DOX. Then, the DOX in the P-DOX/1MT@MM effectively eliminatedo the residual tumor cells and exerted enhanced toxicity. In conclusion, this novel injectable hydrogel that combines chemotherapy and immunotherapy has the property of sequential drug release and is a promising strategy for preventing the postoperative recurrence of tumors.

Current targeting strategies and advanced nanoplatforms for atherosclerosis therapy.

Atherosclerosis is one of the major causes of death worldwide, and it is closely related to many cardiovascular diseases, such as stroke, myocardial infraction and angina. Although traditional surgical and pharmacological interventions can effectively retard or slow down the progression of atherosclerosis, it is very difficult to prevent or even reverse this disease. In recent years, with the rapid development of nanotechnology, various nanoagents have been designed and applied to different diseases including atherosclerosis. The unique atherosclerotic microenvironment with signature biological components allows nanoplatforms to distinguish atherosclerotic lesions from normal tissue and to approach plaques specifically. Based on the process of atherosclerotic plaque formation, this review summarises the nanodrug delivery strategies for atherosclerotic therapy, trying to provide help for researchers to understand the existing atherosclerosis management approaches as well as challenges and to reasonably design anti-atherosclerotic nanoplatforms.

An active transport dual adaptive nanocarrier designed to overcome the corneal microenvironment for neovascularization therapy.

The eyes have a complicated microenvironment with many clearance mechanisms, making it challenging for effective drug delivery to the targeted areas of the eyes. Substrate transport mediated by active transporters is an important way to change drug metabolism in the ocular microenvironment. We designed multifunctional, dual-adaptive nanomicelles (GSCQ@NTB) which could overcome multiple physiological barriers by acting on both the efflux transporter and influx transporter to achieve deep delivery of the P-gp substrate in the cornea. Specifically, an effective "triple" antiangiogenic agent, nintedanib (NTB), was loaded into the biocompatible micelles. The expression of the efflux transporter was reversed by grafting quercetin. The peptide (glycylsarcosine, GS) was modified to target the influx transporter "Peptide Transporter-1" (PepT-1). Quercetin (QRT) and nintedanib (NTB) were transported to the cornea cooperatively, achieving long retention on the ocular surface and high compatibility. In a New Zealand rabbit model, within 8 hours after local administration, GSCQ@NTB was enriched in corneal stromal neovascularization and effectively inhibited the progress of neovascularization. Its effectiveness is slightly better than that in the first-line clinical application of steroids. In this study, we introduce the preparation of a dual adaptive nano-micelle system, which may provide an effective non-invasive treatment for corneal neovascularization.

Biomimetic biomineralization nanoplatform-mediated differentiation therapy and phototherapy for cancer stem cell inhibition and antitumor immunity activation.

Growing evidence suggests that the presence of cancer stem cells (CSCs) is a major challenge in current tumor treatments, especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis. Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy. In this work, we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid (ATRA) via biomineralization. This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters, which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration. With the help of CSC differentiation induced by ATRA, IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner. Furthermore, ATRA can boost immunogenic cell death induced by phototherapy, thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells. Taken together, this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation, improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.

Effect of Ivermectin on the Expression of P-Glycoprotein in Third-Stage Larvae of Haemonchus contortus Isolated from China.

Haemonchus contortus poses a severe hazard to the healthy development of the sheep industry and threatens the welfare of sheep. Ivermectin is the primary anthelmintic used for the prevention and treatment of H. contortus parasitism. However, the widespread and uncontrolled application of ivermectin has resulted in the development and spread of resistant strains of H. contortus. P-glycoprotein (P-gp) plays important roles in the pharmacology and toxicology of ivermectin, and changes in P-gp expression levels can be used to analyze the resistance of H. contortus to ivermectin. This study aimed to analyze the effects of ivermectin on P-gp expression in H. contortus L3 larvae isolated from China and to evaluate whether changes in P-gp expression levels can be used to analyze resistant H. contortus strains. In the absence of drug treatment, the ivermectin-resistant strains isolated in China showed increased expression of P-gp11 (p < 0.01) compared with sensitive strains from elsewhere, whereas the expressions of P-gp2 and P-gp9.1 were downregulated (p < 0.01). When the same strain was compared before and after drug treatment, obvious differences in expression were observed between the different strains. Ivermectin-induced P-gp expression was found to be very complex among the L3 larvae of different strains. In addition, it was confirmed that using P-gp to determine ivermectin resistance in H. contortus strains from different geographic environments can yield different results.

Injectable Zwitterionic Physical Hydrogel with Enhanced Chemodynamic Therapy and Tumor Microenvironment Remodeling Properties for Synergistic Anticancer Therapy.

Surgical resection is the first-line therapy for breast cancer. However, residual tumor cells and the highly immunosuppressive tumor microenvironment (TME) continue to have a serious impact on tumor recurrence and metastasis postresection. Implantation of an in situ hydrogel system postresection has shown to be an effective treatment with great clinical potential. Herein, an injectable zwitterionic hydrogel system was developed for local drug delivery with enhanced immune activation and prevention of tumor recurrence. Driven by electrostatic interactions, poly(sulfobetaine methacrylate) (PSBMA) self-assembles into a hydrogel in saline, achieving low protein adsorption and tunable biodegradability. The chemotherapy drug doxorubicin (DOX) was loaded into copper peroxide nanoparticles (CuO2/DOX), which were coated with macrophage membranes to form tumor-targeting nanoparticles (M/CuO2/DOX). Next, M/CuO2/DOX and the stimulator of interferon genes (STING) agonist 2',3'-cGAMP were coloaded into PSBMA hydrogel (Gel@M/CuO2/DOX/STING). The hydrophilic STING agonist was first released by diffusion from hydrogel to activate the STING pathway and upregulate interferon (IFN) signaling related genes, remodeling the immunosuppressive TME. Then, M/CuO2/DOX targeted the residual tumor cells, combining with DOX-induced DNA damage, immunogenic tumor cell death, and copper death. Hence, this work combines chemodynamic therapy with STING pathway activation in TME, encouraging residual tumor cell death, promoting the maturation of dendritic cells, enhancing tumor-specific CD8+ T cell infiltration, and preventing postoperative recurrence and metastasis.

A dual-sensitive nanoparticle-mediated deepening synergistic therapy strategy involving DNA damage and ICD stimuli to treat triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most aggressive cancers with an immunosuppressive microenvironment, and achieving a satisfactory effect from monotherapies, such as chemotherapy, photodynamic therapy (PDT) or immunotherapy, remains difficult. To solve this puzzle, a deepening synergistic therapy strategy of DNA damage and immunogenic cell death (ICD) stimuli was proposed. We engineered a doxorubicin (DOX) and 4-(hydroxymethyl) phenylboronic acid pinacol ester (PBAP) prodrug polymer, and encapsulated chlorin e6 (Ce6) to obtain the hyaluronidase (HAase) and H2O2 dual-sensitive responsive nanoparticles (Ce6/HDP NPs). The NPs displayed efficient intratumoral accumulation and cellular internalization properties due to the active targeting of the hyaluronic acid (HA). The dual DNA damage of the chemotherapy and ROS production directly caused tumor cell apoptosis. The strong ICD stimuli, which were induced by ROS production and GSH depletion, generated an amplified immunogenicity to activate tumor immunotherapy in vivo. In this manner, the NPs could significantly inhibit primary tumor, abscopal tumor, pulmonary metastasis and recurrent tumor in a subcutaneous 4T1 tumor model, with effective biosafety. This study has provided a promising deepening synergistic therapy strategy against TNBC.

A Vanadium-Based Nanoplatform Synergizing Ferroptotic-like Therapy with Glucose Metabolism Intervention for Enhanced Cancer Cell Death and Antitumor Immunity.

Ferroptosis activation has been considered a mighty weapon for cancer treatment, and growing attention is being paid to reinforcing tumor cells' sensitivity to ferroptosis. However, the existence of certain ferroptosis resistance mechanisms, especially the abnormal metabolism of tumor cells, has long been underestimated. We propose an enhanced ferroptosis-activating pattern via regulating tumor cells' glycometabolism and construct a nanoplatform named PMVL, which is composed of lonidamine (LND)-loaded tannic acid coordinated vanadium oxides with the camouflage of PD-L1 inhibiting peptide-modified tumor cell membrane. This work reveals that the mixed valence of vanadium (VIV and VV) in PMVL triggers ferroptosis due to the self-cyclic valence alteration of V, the process of which generates •OH for lipid peroxide accumulation (VIV → VV) and depletes glutathione (GSH) for glutathione peroxidase (GPX4) deactivation (VV → VIV). Notably, LND strengthens ferroptosis by dual suppression of glycolysis (decreasing ATP supply) and the pentose phosphate pathway (decreasing NADPH production), causing anabatic GSH consumption. Besides, the inhibited glycolysis generates less intracellular lactic acid and alleviates the acidity of tumor microenvironment, preventing immunosuppressive M2 macrophage polarization. In vitro and in vivo data demonstrate the glycometabolism-intervention-enhanced ferroptosis and boosted immunity activation, potentially providing opportunities and possibilities for synergetic cancer therapy.

Cellular drug delivery system for disease treatment.

The application of variable novel drug delivery system has shown a flowering trend in recent years. Among them, the cell-based drug delivery system (DDS) utilizes the unique physiological function of cells to deliver drugs to the lesion area, which is the most complex and intelligent DDS at present. Compared with the traditional DDS, the cell-based DDS has the potential of prolonged circulation in body. Cellular DDS is expected to be the best carrier to realize multifunctional drug delivery. This paper introduces and analyzes common cellular DDSs such as blood cells, immune cells, stem cells, tumor cells and bacteria as well as relevant research examples in recent years. We hope that this review can provide a reference for future research on cell vectors and promote the innovative development and clinical transformation of cell-based DDS.

Transcriptomics and Proteomics of Haemonchus contortus in Response to Ivermectin Treatment.

A major problem faced by the agricultural industry is the resistance of Haemonchus contortus to anthelmintic drugs. For a better understanding of the response of H. contortus to IVM and for the screening of drug-resistance-related genes, we used RNA sequencing and isobaric tags for relative and absolute quantification (iTRAQ) technology to detect the transcriptomic and proteomic changes in H. contortus after ivermectin treatment. An integrated analysis of the two omics showed that the differentially expressed genes and proteins were significantly enriched in the pathways of amino acid degradation, the metabolism of xenobiotics by cytochrome P450, the biosynthesis of amino acids, and the tricarboxylic acid cycle. We found that the upregulated UDP-glycosyltransferases (UGT), glutathione S-transferase (GST), cytochrome P450 (CYP), and p-glycoprotein (Pgp) genes play important roles in drug resistance in H. contortus. Our work will help in the understanding of the transcriptome and proteome changes in H. contortus after IVM and will facilitate the discovery of genes related to drug resistance. This information can be further applied to increase the understanding of the response of IVM in relation to H. contortus.

Research progress of exosomes as drug carriers in cancer and inflammation.

Extracellular vesicles (EVs) could be produced by most cells and play an important role in disease development. As a subtype of EVs, exosomes exhibit suitable size, rich surface markers and diverse contents, making them more appealing as potential drug carriers. Compared with traditional synthetic nanoparticles, exosomes possess superior biocompatibility and much lower immunogenicity. This work reviewed the most up-to-date research progress of exosomes as carriers for nucleic acids, proteins and small molecule drugs for cancer and inflammation management. The drug loading strategies and potential cellular uptake behaviour of exosomes are highlighted, trying to provide reference for future exosome design and application.

Exosomes are secreted by a variety of cells and play an important role in the process of inter-cell communication.This paper provides a comprehensive review focussing on the up-to-date applications of exosomes as carriers of nucleic acids, proteins and small molecule drugs for cancer and inflammation management.This paper briefly introduces the basic properties of exosomes, from definition, biogenesis to cellular uptake manners.Various strategies to enable exosomes to efficiently load cargoes are highlighted.Problems to be solved when using exosomes to deliver drugs are discussed.

Multifunctional biomimetic nanoplatform based on photodynamic therapy and DNA repair intervention for the synergistic treatment of breast cancer.

Photodynamic therapy (PDT) is a minimally invasive and locally effective treatment method, which has been used in the clinical treatment of a variety of superficial tumors. In recent years, PDT has received extensive attention due to its induction of immunogenic cell death (ICD). However, the repair mechanism of tumor cells and low immune response limit the further development of PDT. To this end, a multifunctional biomimetic nanoplatform 4T1Mem@PGA-Ce6/Ola (MPCO) is developed to co-deliver the photosensitizer Chlorin e6 (Ce6) and Olaparib (Ola) with the function of preventing DNA repair. The nanoplatform shows efficient tumor targeting and cellular internalization properties due to cell membrane camouflage, and Ce6 and Ola produce a significant synergistic anti-tumor effect under laser irradiation. Meanwhile, the nanoplatform can also activate the cyclic guanosine monophosphate-adenosine monophosphate synthase-interferon gene stimulator signaling (cGAS-STING) pathway to produce cytokines. The damage-associated molecular patterns induced by ICD can work with these cytokines to recruit and stimulate the maturation of dendritic cells and induce the systemic anti-tumor immune response. Overall, this multifunctional biomimetic nanoplatform integrating PDT, chemotherapy, and immunotherapy is highlighted here to boost anti-tumor therapy. STATEMENT OF SIGNIFICANCE: Self-repair of DNA damage is the most important reason for the failure of primary tumor eradication and the formation of secondary and metastatic tumors. To address this issue, a multifunctional biomimetic nanoplatform 4T1Mem@PGA-Ce6/Ola (MPCO) was developed to integrate a photosensitizer Chlorine a6 and a poly (ADP-ribose) polymerase inhibitor Olaparib. With tumor targeting ability and controlled release of drugs, the MPCO was expected to enhance tumor immunogenicity and facilitate antitumor immunity through the induction of immunogenic cell death as well as the activation of the cGAS-STING pathway. This study develops a promising combination strategy against tumors and has substantial implications for the prognosis of patients with breast cancer.

Salt sensitive purely zwitterionic physical hydrogel for prevention of postoperative tissue adhesion.

Abdominal adhesions are a class of serious complications following abdominal surgery, resulting in a complicated and severe syndrome and sometimes leading to a Gordian knot. Traditional therapies employ hydrogels synthesized using complicated chemical formulations-often with click chemistry or thermal responsive hydrogel. The complicated synthesis process and severe conditions limit the extent of the hydrogels' applications. In this work, poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) polymer was synthesized to self-assemble into physical hydrogels due to the inter- and intramolecular ion interactions. The strong static interaction bonding density has a substantial impact on the gelation and physicochemical properties, which is beneficial to clinical applications and offers a novel way to obtain the desired hydrogel for a specific biomedical application. Intriguingly, this PSBMA polymer can be customized into a transient network with outstanding antifouling capability depending on the ion concentration. As ion concentration increases, the PSBMA hydrogel dissociated completely, endowing it as a candidate for adhesion prevention. In the cecum-sidewall model, the PSBMA hydrogel demonstrated superior anti-adhesion properties than commercial HA hydrogel. Furthermore, we have demonstrated that this PSBMA hydrogel could inhibit the inflammatory response and encourage anti-fibrosis resulting in adhesion prevention. Most surprisingly, the recovered skins of cecum and sidewall are as smooth as the control skin without any scar and damage. In conclusion, a practical hydrogel was synthesized using a facile method based on purely zwitterionic materials, and this ion-sensitive, antifouling adjustable supramolecular hydrogel with great clinic transform potential is a promising barrier for preventing postoperative tissue adhesion. STATEMENT OF SIGNIFICANCE: The development of hydrogels with satisfactory coverage, long retention time, facile synthetic method, and good biocompatibility is vital for preventing peritoneal adhesions. Herein, we developed a salt sensitive purely zwitterionic physical hydrogel poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) hydrogel to effectively prevent postoperative and recurrent abdominal adhesions. The hydrogel was simple to synthesize and easy to use. In the cecum-sidewall model, PSBMA hydrogel could instantaneously adhere and fix on irregular surfaces and stay in the wound for more than 10 days. The PSBMA hydrogel could inhibit the inflammatory response, encourage anti-fibrosis, and restore smoothness to damaged surfaces resulting in adhesion prevention. Overall, the PSBMA hydrogel is a promising candidate for the next generation of anti-adhesion materials to meet clinical needs.

Oxygen-boosted biomimetic nanoplatform for synergetic phototherapy/ferroptosis activation and reversal of immune-suppressed tumor microenvironment.

Photodynamic therapy (PDT) induces apoptosis of cancer cells by generating cytotoxic reactive oxygen species, the therapeutic effect of which, however, is impeded by intrinsic/inducible apoptosis-resistant mechanisms in cancer cells and hypoxia of tumor microenvironment (TME); also, PDT-induced anti-tumor immunity activation is insufficient. To deal with these obstacles, a novel biomimetic nanoplatform is fabricated for the precise delivery of photosensitizer chlorin e6 (Ce6), hemin and PEP20 (CD47 inhibitory peptide), integrating oxygen-boosted PDT, ferroptosis activation and CD47-SIRPα blockade. Hemin's catalase-mimetic activity alleviates TME hypoxia and enhances PDT. The nanoplatform activates ferroptosis via both classical (down-regulating glutathione peroxidase 4 pathway) and non-classical (inducing Fe2+ overload) modes. Besides the role of hemin in consuming glutathione and up-regulating heme oxygenase-1 expression, interestingly, we observe that Ce6 enhance ferroptosis activation via both classical and non-classical modes. The anti-cancer immunity is reinforced by combining PEP20-mediated CD47-SIRPα blockade and PDT-mediated T cell activation, efficiently suppressing primary tumor growth and metastasis. PEP20 has been revealed for the first time to sensitize ferroptosis by down-regulating system Xc-. This work sheds new light on the mechanisms of PDT-ferroptosis activation interplay and bridges immunotherapy and ferroptosis activation, laying the theoretical foundation for novel combinational modes of cancer treatment.

Evaporative Deposition of Surfactant-Laden Nanofluid Droplets over a Silicon Surface.

Morphologies of evaporative deposition, which has been widely applied in potential fields, were induced by the competition between internal flows inside evaporating droplets. Controlling the pattern of deposition and suppressing the coffee-ring effect are essential issues of intense interest in the aspects of industrial technologies and scientific applications. Here, evaporative deposition of surfactant-laden nanofluid droplets over silicon was experimentally investigated. A ring-like deposition was formed after complete evaporation of sodium dodecyl sulfate (SDS)-laden nanofluid droplets with an initial SDS concentration ranging from 0 to 1.5 CMC. In the case of initial SDS concentrations above 1.3 CMC, no cracks were observed in the ring-like deposition, indicating that the deposition patterns of nanofluid droplets could be completely changed and cracks could be eliminated by sufficient addition of SDS. With the increase of the initial concentration of hexadecyl trimethylammonium bromide (CTAB), the width of the deposition ring gradually decreased until no ring-like structure was formed. On the contrary, with the increase of the initial Triton X-100 (TX-100) concentration, the width of the deposition ring gradually increased until a uniform deposition was generated. Moreover, when the initial TX-100 concentration was high, a "tree-ring-like" pattern was discovered. Besides, morphologies of evaporative pattern due to the addition of surfacants were qualitatively analyzed.

Effects of different types of heat wave days on ozone pollution over Beijing-Tianjin-Hebei and its future projection.

There are concerns that in the 21st century, global warming will lead to more frequent heat wave days (HWDs), which could amplify ozone pollution (OP). However, a recent study projected that future atmospheric circulation variations may benefit OP control in Beijing-Tianjin-Hebei (BTH). To investigate the possible reasons for this contradiction, this paper discussed the ozone amplification capacity between different HWD types and their future projections based on observations and Community Earth System Model Large Ensemble Simulations (CESM-LENS). Composite analysis shows that not all HWDs amplify the OP in BTH. The main factor determining whether HWDs aggravate OP is the accompanying circulation anomalies rather than the intensity of the HWDs. The HWDs that aggravate ozone pollution are usually accompanied by stable saddle-like circulation anomalies and atmospheric blocking (blocking HWDs), which weaken the meridional temperature gradient and strengthen atmospheric stability. In contrast, HWDs with wave-train circulation anomalies have a limited ability to exacerbate OP in BTH due to their weak atmospheric stability. We introduce the Ozone Weather Index (OWI) to discern the influence of meteorological conditions on OP and overcome the lack of ozone concentration data in CESM-LENS under RCP 8.5 scenario. The OWI shows a significant downward trend in the 21st century, which indicates that the summer mean atmospheric circulation variations are beneficial for OP control in BTH. However, the frequency of blocking HWDs, which could amplify OP, will increase significantly in the 21st century. By the end of the 21st century, the frequency of blocking HWDs will be three times more than that of the end of 20th century. These findings inform policymakers that it is imperative to consider the mean climate state and the risks associated with extreme events when formulating future ozone pollution control policies.

Interannual relationship between displacement and intensity of East Asian jet stream and haze over eastern China in winter.

A recent case study indicated that the weakening of the East Asian subtropical jet was an important cause of the severe haze in North China in the winter of 2015. However, the interannual relationship between two key features, the displacement and the intensity of the East Asian jet stream (EAJS) and the haze days over eastern China (HDEC), remains unclear. Observed data, ERA-Interim reanalysis, and Community Earth System Model Large Ensemble Numerical Simulation(CESM-LENS) were used to investigate the interannual relationship between the EAJS and HDEC during the winter season from 1980 to 2017 and its possible associated atmospheric mechanisms. The results show that the northward movement of the EAJS is conducive to more HDEC by weakening synoptic-scale transient eddy activities (STEA) and baroclinicity, forming an upper-level anticyclonic anomaly over eastern China (EC). The local meteorological conditions (e.g., stronger temperature inversion potential, higher relative humidity, descending motion) are favorable for the accumulation of HDEC, showing consistent variations in more haze in the entire region of EC. The southward movement of the EAJS has the opposite effect. The strong East Asian subtropical jet (weak polar-front jet) could result in the distribution of the meridional dipole with less haze in north EC and more haze in south EC. The mean flow loses energy to the STEA over north EC and increases the baroclinicity, which is favorable for dispersing HDEC. However, the configuration of upper-level cyclonic and low-level southwest wind anomalies that appeared in south EC weakened the STEA, which favored the accumulation of HDEC. The observed results were further verified by CESM-LENS.

Research progress of tumor targeted drug delivery based on PD-1/PD-L1.

Over activation of immune checkpoint pathways assists tumor cells to escape the surveillance of immune system, resulting in generation and development of tumor. Drugs blocking immune checkpoints target lymphocyte receptors or their ligands to enhance endogenous antitumor activity by activating the immune system. The drugs targeting PD-1/PD-L1 axis have achieved favourable clinical efficacy, less and controllable toxicity and side effects. However, only a part of patients benefit from immunotherapy, so the problem of increasing the response rate of patients is on the agenda. Meanwhile, there are still some problems such as how to achieve the long-term response to most metastatic or non operative malignant tumors, and minimize the side effects of immune checkpoint inhibitor (ICI). Therefore, scientists are actively exploring methods, such as combining anti-PD-1 therapy with various traditional or newly developed therapeutic methods and building a tumor targeted drug delivery system to maximize the efficacy of drugs and reduce side effects. In this review, we summarized the related concepts and mechanism of PD-1 and its ligands PD-L1, and introduced certain drugs targeting PD-1/PD-L1 axis, their clinical effects and safety issues. Finally, a variety of combination therapies based on PD-1/PD-L1 and the application of different nanocarriers aiming at reducing non-targeting effect and improving the efficacy were discussed.

Using feeding and motility patterns for ivermectin resistance detecting in Haemonchus contortus larvae.

Resistance of Haemonchus contortus to ivermectin has become an increasingly serious problem worldwide. Drug-based control and management of this parasite requires reliable methods for testing drug resistance to evaluate and monitor their anthelmintic effects. In this study, the larval migration inhibition test (LMIT) and the larval feeding inhibition test (LFIT) were used to assess and compare seven strains of H. contortus, including one resistant and one susceptible strain from abroad (UKR and ASS, respectively), and five strains native to China (SXS, WMR, WSR1, WSR2, and WSR3). LFIT results showed that fluorescent-labeled Escherichia coli could be clearly observed after ivermectin (IVM) treatment inside UKR, WMR, WSR1, WSR2, and WSR3 larvae, but not inside ASS and SXS strains. Moreover, LMIT results showed that migration of SXS strain did not change significantly after IVM treatment compared with the susceptible ASS strain, whereas migration increased significantly in the UKR, WMR, WSR1, WSR2, and WSR3 strains. Taken together, SXS was found to be an IVM-susceptible strain, whereas WMR, WSR1, WSR2, and WSR3 were IVM-resistant strains. These results demonstrate that assessment of the motility and feeding ability of H. contortus larvae can be effectively used to determine resistance of H. contortus to IVM.