The AaERF64-AaTPPA module participates in cold acclimatization of Actinidia arguta (Sieb. et Zucc.) Planch ex Miq.

Actinidia arguta (A. arguta, kiwiberry) is a perennial deciduous vine with a strong overwintering ability. We hypothesized that trehalose metabolism, which plays a pivotal role in the stress tolerance of plants, may be involved in the cold acclimatization of A. arguta. Transcriptome analysis showed that the expression of AaTPPA, which encodes a trehalose-6-phosphate phosphatase (TPP), was upregulated in response to low temperatures. AaTPPA expression levels were much higher in lateral buds, roots, and stem cambia than in leaves in autumn. In AaTPPA-overexpressing (OE) Arabidopsis thaliana (A. thaliana), trehalose levels were 8-11 times higher than that of the wild type (WT) and showed different phenotypic characteristics from WT and OtsB (Escherichia coli TPP) overexpressing lines. AaTPPA-OE A. thaliana exhibited significantly higher freezing tolerance than WT and OtsB-OE lines. Transient overexpression of AaTPPA in A. arguta leaves increased the scavenging ability of reactive oxygen species (ROS) and the soluble sugar and proline contents. AaERF64, an ethylene-responsive transcription factor, was induced by ethylene treatment and bound to the GCC-box of the AaTPPA promoter to activate its expression. AaTPPA expression was also induced by abscisic acid. In summary, the temperature decrease in autumn is likely to induce AaERF64 expression through an ethylene-dependent pathway, which consequently upregulates AaTPPA expression, leading to the accumulation of osmotic protectants such as soluble sugars and proline in the overwintering tissues of A. arguta. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01475-8.

Meta-analysis of the efficacy of Jingjin acupuncture therapy in the treatment of spastic cerebral palsy.

Background: This study aimed to systematically evaluate the clinical efficacy of Jingjin (muscle region of the meridian, sinew/tendon/fascia) acupuncture therapy for the treatment of spastic cerebral palsy. Methods: Computer searches of the Cochrane Library, Web of Science, PubMed, Embase, Chinese Biomedical Literature (CBM) Database, Wanfang database, Wipu (VIP) database, and China National Knowledge Infrastructure (CNKI) database for published randomized controlled trial (RCT) studies on Jingjin acupuncture treatment of cerebral palsy from the beginning of the database construction until 30 November 2023 were performed, and the quality of the papers was assessed through independent data extraction by two individuals and then meta-analyzed using RevMan5.4 software. A total of 20 RCTs involving 1,453 patients were included. Results: The overall effective rate of Jingjin acupuncture therapy was better than that of conventional therapy, with a combined odds ratio (OR) of 4.70 and a 95% confidence interval (CI) of [3.05, 7.24]. The Modified Ashworth Spasticity (MAS) Scale, Gross Motor Function Measure (GMFM), Fine Motor Function Measure (FMFM), and Comprehensive Spasticity Scale (CSS) scores are superior to conventional therapy. Conclusion: Jingjin acupuncture therapy is effective in treating spastic cerebral palsy and has better overall efficacy than conventional therapy. Due to the low quality of some of the literature in this study type, more high-quality, well-designed clinical studies are needed to validate it.

Value of 2D speckle tracking technique combined with real-time 3-dimensional echocardiography in the evaluation of the right atrial function in patients with 3-branch coronary artery disease without myocardial infarction.

To evaluate the right atrial function in patients with 3-branch coronary artery disease (TBCAD) without myocardial infarction by 2D speckle tracking echocardiography (2D-STE) combined with real-time 3-dimensional echocardiography (RT-3DE). Fifty-six patients admitted to our hospital without myocardial infarction with TBCAD were selected. We divided them into 2 groups according to the coronary angiography results: 28 patients in group B (the rate of stenosis is 50% ~< 75%); 28 patients in group C (the rate of stenosis is ≥75%); in addition, 30 healthy volunteers were screened as group A. All subjects underwent RT-3DE to obtain the right atrial volume (RAVmax, RAVmin, and RAVp), and then we calculated the right atrial passive and active ejection fraction (RAPEF, RAAEF), and maximum volume index (RAVImax). In addition, to measure the strain rates (RASRs, RASRe, RASRa) of the right atrium during systole, early diastole, and late diastole, 2D-STE was applied. Correlations between the 2D-STE parameters and the results of N-terminal pro-brain natriuretic peptide (NT-proBNP) and Gensini scores were analyzed by Pearson linear analysis. Compared with group A, RAPEF and RASRe were reduced, while RAAEF and RASRa were elevated in group B (P < .05). RAPEF, RASRs, RASRe, and RASRa were decreased compared with groups A and B, while RAVmax, RAVmin, RAVp, RAVImax, and RAAEF were increased in group C (P < .05). There was a significant correlation between 2D-STE parameters and the results of NT-proBNP and Gensini scores (P < .05). The storage, conduit, and pump functions of the right atrium are reduced in patients with 3-branch coronary artery disease without myocardial infarction; 2D-STE combined with RT-3DE is valuable in the evaluation of the right atrium in patients with coronary artery disease.

Chinese cities show different trend toward carbon peak.

Understanding the disparities in carbon emission trend among cities is critical for achieving carbon peak goal. However, the status and trends of carbon peaking and reduction in various city types are still unclear. Therefore, this study classified 315 Chinese cities according to their economic and industrial structure by SOM-K-means, aiming to evaluate the trends and dynamic drivers of carbon peaking progress in different city types. The findings reveal a decline in carbon emissions in 110 cities (34.9 %) since 2020. Notably, all city types show potential for carbon reduction and achieving carbon peaking. Specifically, resource-based cities and high-end service cities have the most effect on reducing emissions, with 48.4 % and 42.1 % of the cities declining in carbon emissions. Energy-based and heavy industrial cities face heightened pressure to reduce carbon emissions. Additionally, in high-end service cities, energy efficiency and investment intensity contribute to emission reduction, while industrial structure adjustment decrease carbon emissions in resource-based cities. Furthermore, enhancing energy efficiency effects and R&D intensity are effective ways to significantly reduce carbon emissions in heavy industrial cities. We conclude that differentiating carbon reduction pathways for different cities should constitute be a breakthrough in achieving the goal of carbon peaking. These insights provide recommendations for cities that have yet to reach their carbon peak for both China and other developing countries.

Seeded Growth of Size-Tunable Au@Ag Core-Shell Nano-Octahedra and Their Yolk-Shell Derivatives for Near Infrared Photothermal Conversion.

Gold-based nanostructures with well-defined morphologies and hollow interiors have significant potential as a versatile platform for various plasmonic applications including biomedical diagnostics and sensing. In this study, we report the synthesis of Au@Ag core-shell nanocrystals with perfect octahedral shapes and tunable edge lengths via seeded growth. These nanocrystals were then oxidatively carved into yolk-shell nanocages with a retained octahedral morphology. The increase in octahedral edge length and volume of the interior hollow cavity synergistically leads to a red-shift of the LSPR peak. As a result, the optimized Au@AuAg yolk-shell octahedral nanocages showed a remarkable temperature increase of 23 °C upon 15 min irradiation of an 808 nm laser at a power density of 1 W cm-2. This study provides a feasible strategy for creating octahedral AuAg nanostructures with tunable sizes and hollow interiors and validates their promising use in NIR photothermal conversion.

Computational Insights into Cyclodextrin Inclusion Complexes with the Organophosphorus Flame Retardant DOPO.

Cyclodextrins (CDs) were used as green char promoters in the formulation of organophosphorus flame retardants (OPFRs) for polymeric materials, and they could reduce the amount of usage of OPFRs and their release into the environment by forming [host:guest] inclusion complexes with them. Here, we report a systematic study on the inclusion complexes of natural CDs (α-, ß-, and γ-CD) with a representative OPFR of DOPO using computational methods of molecular docking, molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations. The binding modes and energetics of [host:guest] inclusion complexes were analyzed in details. α-CD was not able to form a complete inclusion complex with DOPO, and the center of mass distance [host:guest] distance amounted to 4-5 Å. ß-CD and γ-CD allowed for a deep insertion of DOPO into their hydrophobic cavities, and DOPO was able to frequently change its orientation within the γ-CD cavity. The energy decomposition analysis based on the dispersion-corrected density functional theory (sobEDAw) indicated that electrostatic, orbital, and dispersion contributions favored [host:guest] complexation, while the exchange-repulsion term showed the opposite. This work provides an in-depth understanding of using CD inclusion complexes in OPFRs formulations.

A first-principles study on the promising thermoelectric properties of SnX (X = S, Se, Te) compounds.

SnSe has emerged as an outstanding thermoelectric material due to its exceptional performance. In this study, first-principles calculations are employed to investigate the thermoelectric properties of materials within the SnX family, where X can be either S, Se, or Te. Initially, we assessed the stability of SnX (X = S, Se, Te). We found that SnS exhibits better mechanical and thermal stability than SnSe and SnTe. We then conduct phonon and electronic transport analysis. Following the general rule that heavier atoms have lower thermal conductivity, SnTe demonstrates lower thermal conductivity due to its low group velocity compared with SnS and SnSe. Regarding electrical transport properties, the band gaps for SnS, SnSe, and SnTe are 0.56, 0.54, and 0.35 eV, respectively. Notably, the small band gap and higher degeneracy in its band valleys for SnTe make it more effective for achieving a high power factor. The maximum ZT values are determined to be 1.41, 1.41, and 1.87 for SnS, SnSe, and SnTe, respectively. Remarkably, ZTmax of SnTe exceeds that of SnSe by 32.6%. Overall, the results clearly demonstrate that SnTe exhibits superior thermoelectric properties compared to SnSe and SnS. This study provides valuable insights into the electronic structure, thermal conductivity, and mechanical and thermal stability of materials within the SnSe family, such as SnS or SnTe, without the need for extensive and costly experimental work.

Functions of Basic Helix-Loop-Helix (bHLH) Proteins in the Regulation of Plant Responses to Cold, Drought, Salt, and Iron Deficiency: A Comprehensive Review.

Abiotic stresses including cold, drought, salt, and iron deficiency severely impair plant development, crop productivity, and geographic distribution. Several bodies of research have shed light on the pleiotropic functions of BASIC HELIX-LOOP-HELIX (bHLH) proteins in plant responses to these abiotic stresses. In this review, we mention the regulatory roles of bHLH TFs in response to stresses such as cold, drought, salt resistance, and iron deficiency, as well as in enhancing grain yield in plants, especially crops. The bHLH proteins bind to E/G-box motifs in the target promoter and interact with various other factors to form a complex regulatory network. Through this network, they cooperatively activate or repress the transcription of downstream genes, thereby regulating various stress responses. Finally, we present some perspectives for future research focusing on the molecular mechanisms that integrate and coordinate these abiotic stresses. Understanding these molecular mechanisms is crucial for the development of stress-tolerant crops.

Genome-wide analysis of gustatory receptor genes and identification of the fructose gustatory receptor in Arma chinensis.

Gustatory receptors (GRs) allow insects to sense tastes in their external environment. Gustatory perception is crucial for distinguishing between beneficial and harmful or toxic compounds, affecting survival. This study is the first to identify and classify the GR genes and investigate their expression in the predatory Arma chinensis. Thirteen GR genes (ArmaGr1-ArmaGr13) were identified and classified into four families via phylogenetic analysis. In the predacious developmental stages, ArmaGr7 expression gradually increased from the 2nd to 5th instar stages and then to adults. However, ArmaGr7 was also highly expressed in the non-predation 1st instar nymph and egg stages. ArmaGr7 expression was localized in the antennae, scalpella, forelegs, wings, head, and midgut of male and female adults, with wings displaying the highest expression. Furthermore, ArmaGr7 expression was positively correlated with fructose solution intake; molecular docking results showed that fructose could effectively dock withArmaGr7. A protein structure comparison revealed that the ArmaGr7 structure was different from that of other GR43a-like proteins, which may be related to the gene splicing of the A. chinensis GR gene. These results elucidate the crucial role of ArmaGr7 in fructose recognition by A. chinensis and provide a foundation for further studies on gustatory perception.

Alpha 2-adrenoceptor participates in anti-hyperalgesia by regulating metabolic demand.

The α2-adrenoceptor agonist dexmedetomidine is a commonly used drug for sedatives in clinics and has analgesic effects; however, its mechanism of analgesia in the spine remains unclear. In this study, we systematically used behavioural and transcriptomic sequencing, pharmacological intervention, electrophysiological recording and ultrasound imaging to explore the analgesic effects of the α2-adrenoceptor and its molecular mechanism. Firstly, we found that spinal nerve injury changed the spinal transcriptome expression, and the differential genes were mainly related to calcium signalling and tissue metabolic pathways. In addition, α2-adrenoceptor mRNA expression was significantly upregulated, and α2-adrenoceptor was significantly colocalised with markers, particularly neuronal markers. Intrathecal dexmedetomidine suppressed neuropathic pain and acute inflammatory pain in a dose-dependent manner. The transcriptome results demonstrated that the analgesic effect of dexmedetomidine may be related to the modulation of neuronal metabolism. Weighted gene correlation network analysis indicated that turquoise, brown, yellow and grey modules were the most correlated with dexmedetomidine-induced analgesic effects. Bioinformatics also annotated the involvement of metabolic processes and neural plasticity. A cardiovascular-mitochondrial interaction was found, and ultrasound imaging revealed that injection of dexmedetomidine significantly enhanced spinal cord perfusion in rats with neuropathic pain, which might be regulated by pyruvate dehydrogenase kinase 4 (pdk4), cholesterol 25-hydroxylase (ch25 h) and GTP cyclohydrolase 1 (gch1). Increasing the perfusion doses of dexmedetomidine significantly suppressed the frequency and amplitude of spinal nerve ligation-induced miniature excitatory postsynaptic currents. Overall, dexmedetomidine exerts analgesic effects by restoring neuronal metabolic processes through agonism of the α2-adrenoceptor and subsequently inhibiting changes in synaptic plasticity.

Association of Serum AGR With All-Cause and Cause-Specific Mortality Among Individuals With Diabetes.

BACKGROUND: There is insufficient data to support a link between serum AGR and mortality in individuals with diabetes. This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. METHODS: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional hazards models. RESULTS: 2415 all-cause deaths, including 688 cardiovascular deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend<0.0001), cardiovascular mortality (Ptrend<0.001), and cancer mortality (Ptrend<0.01) were 0.51(0.42,0.60), 0.62(0.46,0.83), and 0.57(0.39,0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per one-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P<0.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. CONCLUSIONS: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those under age 60 and heavy drinker.

Analysis of Ionomic Profiles of Spinal Cords in a Rat Model with Bone Cancer Pain.

Background: Ionomics is used to study levels of ionome in different states of organisms and their correlations. Bone cancer pain (BCP) severely reduces quality of life of patients or their lifespan. However, the relationship between BCP and ionome remains unclear. Methods: The BCP rat model was constructed through inoculation of Walker 256 cells into the left tibia. Von Frey test, whole-cell patch-clamp recording and inductively coupled plasma mass spectrometry (ICP-MS) technologies were conducted for measuring tactile hypersensitivity, the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) of neurons of spinal slices, and ionome of spinal cord samples, respectively. Principal component analysis (PCA) was used to explore ionomic patterns of the spinal cord. Results: The BCP rat model was successfully constructed through implantation of Walker 256 cells into the left tibia. The frequency and amplitude of mEPSCs of neurons in the spinal cord slices from the BCP model rats were notably greater than those in the sham control. In terms of ionomics, the spinal cord levels of two macroelements (Ca and S), four microelements (Fe, Mn, Li and Sr) and the toxic element Ti in the BCP group of rats were significantly increased by inoculation of Walker 256 cancer cells, compared to the sham control. In addition, the correlation patterns between the elements were greatly changed between the sham control and BCP groups. PCA showed that inoculation of Walker 256 cells into the tibia altered the overall ionomic profiles of the spinal cord. There was a significant separation trend between the two groups. Conclusion: Taken together, inoculation of Walker 256 cells into the left tibia contributes to BCP, which could be closely correlated by some elements. The findings provided novel information on the relationship between the ionome and BCP.

Multilaminate Energy Storage Films from Entropy-Driven Self-Assembled Supramolecular Nanocomposites.

Composite materials comprising polymers and inorganic nanoparticles (NPs) are promising for energy storage applications, though challenges in controlling NP dispersion often result in performance bottlenecks. Realizing nanocomposites with controlled NP locations and distributions within polymer microdomains is highly desirable for improving energy storage capabilities but is a persistent challenge, impeding the in-depth understanding of the structure-performance relationship. In this study, a facile entropy-driven self-assembly approach is employed to fabricate block copolymer-based supramolecular nanocomposite films with highly ordered lamellar structures, which are then used in electrostatic film capacitors. The oriented interfacial barriers and well-distributed inorganic NPs within the self-assembled multilaminate nanocomposites effectively suppress leakage current and mitigate the risk of breakdown, showing superior dielectric strength compared to their disordered counterparts. Consequently, the lamellar nanocomposite films with optimized composition exhibit high energy efficiency (>90% at 650 MV m-1), along with remarkable energy density and power density. Moreover, finite element simulations and statistical modeling have provided theoretical insights into the impact of the lamellar structure on electrical conduction, electric field distribution, and electrical tree propagation. This work marks a significant advancement in the design of organic-inorganic hybrids for energy storage, establishing a well-defined correlation between microstructure and performance.

Highly sensitive "off-on" sensor based on MXene and magnetic microspheres for simultaneous detection of lung cancer biomarkers - Neuron specific enolase and carcinoembryonic antigen.

In this work, a highly sensitive lung cancer biomarkers detection probe was developed based on Ag and MXene co-functionalized magnetic microspheres. By using carboxyl magnetic microspheres as carrier, MXene was coated repeatedly by Poly (allylamine hydrochloride) (PAH) as interlayer adhesive, and silver particles grown on the surface of MXene in situ can efficiently improve the sensitivity of the probe. The detection of neuron specific enolase (NSE) is mainly through the formation of a specific complex between NSE antigen and antibody, and the release of antibody labeled with amino carbon quantum dots (CQDs) from the surface of Ag nanoparticles (AgNPs), so that the fluorescence is restored and "OFF-ON" is formed. The biosensor exhibits excellently wide linear range (0.0001-1500 ng/mL) and the limit of detection (LOD) is up to 0.03 pg/mL, which is superior to most tumor marker probes based on fluorescence mechanism. Furthermore, we constructed dual detection strategy for NSE and carcinoembryonic antigen (CEA) simultaneously.

Adherence to a healthy lifestyle including sleep and sedentary behaviors and risk of metabolic dysfunction-associated steatotic liver disease in Chinese adults.

OBJECTIVE: Various lifestyle factors including smoking, alcohol, physical activity, sedentary behavior, diet quality, sleep behavior, and overweight have been related to metabolic dysfunction-associated steatotic liver disease (MASLD); however, their joint impact on risk of MASLD is not well known. We prospectively investigated the association between a combination of lifestyle factors and risk of MASLD. METHODS: This prospective cohort study included 13,303 participants (mean age: 39.1 ± 11.3 years, female: 60.1%) in China. A novel healthy lifestyle score was created combining seven healthy factors: not smoking, no alcohol intake, regular physical activity, short sedentary time, healthy diet, healthy sleep, and healthy weight. Incident MASLD cases were ascertained annually by liver ultrasound and cardiometabolic risk factors. Multivariable Cox proportional hazards regression models were used to estimate the association of healthy lifestyle score with risk of MASLD. RESULTS: Within 48,036 person-years of follow-up, 2823 participants developed MASLD. After adjusting for age, sex, education, occupation, household income, personal and family history of disease, and total energy intake, compared with participants with 0-2 healthy lifestyle factors, the multivariable hazard ratios (95% confidence interval) of MASLD were 0.81 (0.73, 0.89), 0.67 (0.61, 0.75), and 0.55 (0.49, 0.62) for healthy lifestyle score of 3, 4, and 5-7, respectively (P for trend <0.0001). Such associations were consistent across subgroup and sensitivity analyses. CONCLUSION: Our results indicate that a higher healthy lifestyle score is associated with a lower risk of MASLD.

PARP1 promotes EGFR-TKI drug-resistance via PI3K/AKT pathway in non-small-cell lung cancer.

PURPOSE: Tyrosine kinase inhibitor (TKI) resistance is the main type of drug resistance in lung cancer patients with epidermal growth factor receptor (EGFR) mutations, but its underlying mechanism remains unclear. The purpose of this work was to investigate the mechanism by which PARP1 regulates EGFR-TKI resistance to identify potential targets for combating drug resistance. METHODS: The GEO databases, TCGA databases, western blot and qPCR studies were used to investigate the expression of PARP1 in lung cancer cells and tissues and its correlation with the prognosis of lung cancer. The expression of PARP1 in lung cancer TKI resistant cell PC9-ER and TKI sensitive cell PC9 was analyzed by qPCR and western blot. After knocking down of PARP1, CCK-8 assays, colony formation, flow cytometry were used to investigate its impact on erlotinib sensitivity, cell survival, cell cycle, and apoptosis. RNA-seq was used to investigate the mechanism by which PARP1 participates in EGFR-TKI resistance, and the results were validated in vitro and in vivo studies. RESULTS: PARP1 was highly expressed in both lung cancer tissues and cells. Subsequently, increased PARP1 expression was observed in PC9-ER compared with its parental cell line. Knockdown of PARP1 increased erlotinib sensitivity, promoted cell apoptosis, and suppressed cell growth. RNA-seq and previous studies have shown that the PI3K/AKT/mTOR/P70S6K pathway is involved in PARP1-mediated TKI resistance, and these results were confirmed by Western blot in vitro and in vivo. CONCLUSION: PARP1 may serve as a potential therapeutic target for reversing EGFR-TKI resistance in NSCLC via the PI3K/AKT/mTOR/P70S6K pathway.

Exploring natural killer cell-related biomarkers in multiple myeloma: a novel nature killer cell-related model predicting prognosis and immunotherapy response using single-cell study.

BACKGROUND: Natural killer cells (NKs) may be involved in multiple myeloma (MM) progression. The present study elucidated the correlation between NKs and the progression of MM using single-cell binding transcriptome probes to identify NK cell-related biomarkers. METHODS: Single-cell analysis was performed including cell and subtype annotation, cell communication, and pseudotime analysis. Hallmark pathway enrichment analysis of NKs and NKs-related differentially expressed genes (DEGs) were conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction (PPI) networks. Then, a risk model was structured based on biomarkers identified through univariate Cox regression analysis and least absolute shrinkage and selection operator regression analysis and subsequently validated. Additionally, correlation of clinical characteristics, gene set enrichment analysis, immune analysis, regulatory network, and drug forecasting were explored. RESULTS: A total of 13 cell clusters were obtained and annotated, including 8 cell populations that consisted of NKs. Utilizing 123 PPI network node genes, 8 NK-related DEGs were selected to construct a prognostic model. Immune cell infiltration results suggested that 11 immune cells exhibited marked differences in the high and low-risk groups. Finally, the model was used to screen potential drug targets to enhance immunotherapy efficacy. CONCLUSION: A new prognostic model for MM associated with NKs was constructed and validated. This model provides a fresh perspective for predicting patient outcomes, immunotherapeutic response, and candidate drugs.

Ultrastable Iodinated Oil-Based Pickering Emulsion Enables Locoregional Sustained Codelivery of Hypoxia Inducible Factor-1 Inhibitor and Anticancer Drugs for Tumor Combination Chemotherapy.

Tumor hypoxia-associated drug resistance presents a major challenge for cancer chemotherapy. However, sustained delivery systems with a high loading capability of hypoxia-inducible factor-1 (HIF-1) inhibitors are still limited. Here, we developed an ultrastable iodinated oil-based Pickering emulsion (PE) to achieve locally sustained codelivery of a HIF-1 inhibitor of acriflavine and an anticancer drug of doxorubicin for tumor synergistic chemotherapy. The PE exhibited facile injectability for intratumoral administration, great radiopacity for in vivo examination, excellent physical stability (>1 mo), and long-term sustained release capability of both hydrophilic drugs (i.e., acriflavine and doxorubicin). We found that the codelivery of acriflavine and doxorubicin from the PE promoted the local accumulation and retention of both drugs using an acellular liver organ model and demonstrated significant inhibition of tumor growth in a 4T1 tumor-bearing mouse model, improving the chemotherapeutic efficacy through the synergistic effects of direct cytotoxicity with the functional suppression of HIF-1 pathways of tumor cells. Such an iodinated oil-based PE provides a great injectable sustained delivery platform of hydrophilic drugs for locoregional chemotherapy.

Hydroclimatic changes on multiple timescales since 7800 y BP in the winter precipitation-dominated Central Asia.

Central Asia (CA) is one of the world's most significant arid regions, which is markedly impacted by global warming. A better understanding of the dynamical processes governing its Holocene climate variability is critical for a better understanding of possible future impacts of climate change in the region. To date, most of the existing CA paleoclimate records are from the summer precipitation-dominated eastern CA (ECA), with few records from the winter precipitation-dominated western CA (WCA). Here, we present a precisely dated (~6‰) and highly resolved (<4-y) record of hydroclimatic variations from the WCA covering the period between 7,774 and 656 y BP. Utilizing multiple proxies (δ18O, δ13C, and Sr/Ca) derived from a stalagmite from the Fergana Valley, Kyrgyzstan, we reveal a long-term drying trend in WCA, which is in contrast with the wetting trend in ECA. We propose that different responses of winter and summer westerly jets to seasonal solar insolation over the past 8,000 y may have resulted in an antiphased precipitation relationship between the WCA and ECA. Our data contain dominant quasiperiodicities of 1,400, 50 to 70, and 20 to 30 y, indicating close connections between the WCA climate and the North Atlantic. We further identified a series of droughts and pluvials on centennial-to-decadal timescales, which may have influenced regional societies and trans-Eurasian culture exchanges during historical and prehistorical times.