Acidity-Actuated Polymer/Calcium Phosphate Hybrid Nanomotor (PCaPmotor) for Penetrating Drug Delivery and Synergistic Anticancer Immunotherapy.

Tumor acidity-driven nanomotors may offer robust propulsion for tumor-specific penetrating drug delivery. Herein, an acidity-actuated poly(amino acid) calcium phosphate (CaP) hybrid nanomotor (PCaPmotor) was designed, using a mPEG-PAsp-PPhe@THZ531 micelle (Poly@THZ) for CaP mineralization accompanied by αPD-L1 antibody encapsulation. Dissolution of the CaP layer in an acidic tumor environment gave off heat energy to propel the nanomotor to augment the cellular uptake and penetration into deeply seated cancer cells while facilitating αPD-L1 release. THZ531 delivered by the PCaPmotor inhibited CDK12 and its down-streamed phosphorylation of RNAP-II to increase the cancer immunogenicity events such as the DNA damage, cell apoptosis, immunogenic cell death, lysosomal function disturbance, and MHC-I upregulation. THZ531 and αPD-L1 cosupplied by PCaPmotor significantly increased the frequency of DCs maturation and intratumoral infiltration of CTLs, but the two free drugs did not. Consequently, the PCaP@THZ/αPD-L1 nanomotor resulted in synergistic anticancer immunotherapy in mice. This acid-actuated PCaPmotor represented a new paradigm for penetrating drug delivery.

Paclitaxel Overload Supramolecular Oxidative Stress Nanoamplifier with a CDK12 Inhibitor for Enhanced Cancer Therapy.

Combination therapy has emerged as a promising approach for treating tumors, although there is room for improvement. This study introduced a novel strategy that combined the enhancement of apoptosis, ferroptosis, and DNA damage to improve therapeutic outcomes for prostate cancer. Specifically, we have developed a supramolecular oxidative stress nanoamplifier, which was comprised of ß-cyclodextrin, paclitaxel, and ferrocene-poly(ethylene glycol). Paclitaxel within the system disrupted microtubule dynamics, inducing G2/M phase arrest and apoptosis. Concurrently, ferrocene utilized hydrogen peroxide to generate toxic hydroxyl radicals in cells through the Fenton reaction, triggering a cascade of reactive oxygen species expansion, reduction of glutathione levels, lipid peroxidation, and ferroptosis. The increased number of hydroxyl radicals and the inhibitory effect of THZ531 on DNA repair mechanisms exacerbated DNA damage within tumor cells. As expected, the supramolecular nanoparticles demonstrated excellent drug delivery ability to tumor cells or tissues, exhibited favorable biological safety in vivo, and enhanced the killing effect on prostate cancer.

Influence of tillage practices on phosphorus forms in aggregates of Mollisols from northeast China.

BACKGROUND: Phosphorus (P) is an essential mineral nutrient for crop growth and development. Much remains unknown regarding the content and distribution of P forms in different soil aggregates as affected by tillage practices. A 3-year field experiment was conducted to investigate the effects of no-tillage (NT), rotary tillage (RT), subsoiling (SS), and deep tillage (DT) on soil aggregate distribution pattern, aggregate-associated P content, and to understand the conversion trend. RESULTS: Tillage has the potential to accelerate the processes in transforming macro-aggregates (> 0.25 mm) into micro-aggregates (< 0.25 mm). Greatest aggregate stability was attained under RT. Total phosphorus (TP) and available phosphorus (AP) under NT were increased by 21.1-82.0% in contrast to other tillage treatments. The NT had high content in inorganic phosphorus (IP), aluminum phosphorus (Al-P), and iron phosphorus (Fe-P) with 416.7, 107.9, and 99.1 mg·kg-1 on average, respectively. Aggregates with a size dimension of < 2 mm were more sensitive than other sizes of aggregates. IP was evenly distributed throughout all aggregates, ranging from 336.3 to 430.6 mg kg-1 . No differences in organic phosphorus (OP) were found in all tillage treatments, while NT promoted the transformation of labile OP to IP. The AP and OP were generally more abundant in aggregates of 2 to 0.25 mm and < 0.25 mm. CONCLUSION: Short-term NT can improve soil structure and increase P reserves, thus, enhancing the conversion of P from being scarce to available. © 2021 Society of Chemical Industry.

Toxic effects of heavy metal Cd and Zn on chlorophyll, carotenoid metabolism and photosynthetic function in tobacco leaves revealed by physiological and proteomics analysis.

To explore the mechanisms underlying the action of the heavy metals Cd and Zn on the photosynthetic function of plant leaves, the effects of 100 µmol L-1 Cd and 200 µmol L-1 Zn stress (the exposure concentrations of Cd and Zn in the culture medium were 2.24 mg kg-1 and 5.36 mg kg-1) on the chlorophyll and carotenoid contents as well as the photosynthetic function of tobacco leaves (Long Jiang 911) were studied. The key proteins in these physiological processes were quantitatively analyzed using a TMT-based proteomics approach. Cd stress was found to inhibit the expression of key enzymes during chlorophyll synthesis in leaves, resulting in a decrease of the Chl content. However, Zn stress did not significantly influence the chlorophyll content. Leaves adapted to Zn stress by upregulating CAO expression and increase the Chl b content. Although the Car content in leaves did not significantly change under either Cd or Zn stress, the expressions of ZE and VDE during Car metabolism decreased significantly under Cd stress. This was accompanied by damages to the xanthophyll cycle and the NPQ-dependent energy dissipation mechanism. In contrast, under Zn stress, leaves adapted to Zn stress by increasing the expression of VDE, thus improving NPQ. Under Cd stress, the expressions of three sets of proteins were significantly down-regulated, including PSII donor-side proteins (PPD3, PPD6, OEE1, OEE2-1, OEE2-2, OEE2-3, and OEE3-2), receptor-side proteins (D1, D2, CP43, CP47, Cyt b559α, Cyt b559ß, PsbL, PsbQ, PsbR, Psb27-H1, and Psb28), and core proteins of the PSI reaction center (psaA, psaB, psaC, psaD, psaE-A, PsaE-B, psaF, psaG, psaH-1, psaK, psaL, psaN, and psaOL). In comparison, only eight of the above proteins (PPD6, OEE3-2, PsbL, PsbQ, Psb27-H1, psaL, and psaOL) were significantly down-regulated by Zn stress. Under Cd stress, both the donor side and the receptor side of PSII were damaged, and PSII and PSI experienced severe photoinhibition. However, Zn stress did not decrease either PSII or PSI activities in tobacco leaves. In addition, the expression of electron transport-related proteins (cytb6/f complex, PC, Fd, and FNR), ATPase subunits, Rubisco subunits, and RCA decreased significantly in leaves under Cd stress. However, no significant changes were observed in any of these proteins under Zn stress. Although Cd stress was found to up-regulate the expressions of PGRL1A and PGRL1B and induce an increase of PGR5/PGRL1-CEF in tobacco leaves, NDH-CEF was significantly inhibited. Under Zn stress, the expressions of ndhH and PGRL1A in leaves were significantly up-regulated, but there were no significant changes in either NDH-CEF or PGR5/PGRL-CEF. Under Cd stress, the expressions of proteins related to Fd-dependent nitrogen metabolism and reactive oxygen species (ROS) scavenging processes (e.g., FTR, Fd-NiR, and Fd-GOGAT) were significantly down-regulated in leaves. However, no significant changes of any of the above proteins were identified under Zn stress. In summary, Cd stress could inhibit the synthesis of chlorophyll in tobacco leaves, significantly down-regulate the expressions of photosynthesis-related proteins or subunits, and suppress both the xanthophyll cycle and NDH-CEF process. The expressions of proteins related to the Fd-dependent nitrogen metabolism and ROS scavenging were also significantly down-regulated, which blocked the photosynthetic electron transport, thus resulting in severe photoinhibition of both PSII and PSI. However, Zn stress had little effect on the photosynthetic function of tobacco leaves.

The negative effect of urologic chronic pelvic pain syndrome on female sexual function: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: To explore the effect of urologic chronic pelvic pain syndrome (UCPPS) on female sexual function. METHODS: Database searches were conducted in PubMed, EMBASE, the Cochrane Library, and Google Scholar for published literature using the Female Sexual Function Index (FSFI) or reporting the prevalence of dyspareunia. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria, and a meta-analysis was performed using STATA 12.0 and RevMan5.3 software to calculate the mean differences (MD) and odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: A total of nine case-control studies enrolling 4965 subjects were investigated. The present meta-analysis results demonstrated a strong correlation between UCPPS and dyspareunia (OR = 11.27, 95% CI: 5.15-24.67, P < 0.00001). The UCPPS group had significantly lower scores in each domain of the FSFI compared with the healthy control group: total score (MD = -11.35, 95% CI: -14.54- - 8.16, P < 0.00001); desire (MD = -1.04, 95% CI: -1.20- - 0.88, P < 0.00001); arousal (MD = -1.78, 95% CI: -2.36- - 1.20, P < 0.00001); lubrication (MD = -2.11, 95% CI: -2.49- - 1.73, P < 0.00001); orgasm (MD = -1.50, 95% CI: -1.72- - 1.28, P < 0.00001); satisfaction (MD = -1.54, 95% CI: -1.97- - 1.12, P < 0.00001); pain (MD = -2.89, 95% CI: -3.63- - 2.14, P < 0.00001). CONCLUSIONS: UCPPS had a significantly negative effect on female sexual function, particularly in the lubrication, pain, and total score domains. In addition, UCPPS patients had a significantly higher risk of dyspareunia. Psychosocial variables may be a potential pathogenesis of female sexual dysfunction (FSD). Future well-designed research is called for to develop a comprehensive estimate of the association between UCPPS and FSD.

Two new steroidal glycosides from Cynanchum otophyllum Schneid.

Two new C21 steroidal glycosides were isolated from Cynanchum otophyllum Schneid. Their structures were elucidated as qinyangshengenin-3-O-ß-d-digitoxopyranoside (1) and rostratamine-3-O-ß-d-cymaropyranosyl-(1 â†’ 4)-ß-d-digitoxopyranoside (2) on the basis of chemical and spectroscopic methods, including 1D and 2D NMR experiments.

Multimodal Nanoplatform with ROS Amplification to Overcome Multidrug Resistance in Prostate Cancer via Targeting P-Glycoprotein and Ferroptosis.

Chemotherapy remains the most essential treatment for prostate cancer, but multidrug resistance (MDR) contributes to chemotherapy failure and tumor-related deaths. The overexpression of P-glycoprotein (P-gp) is one of the main mechanisms behind MDR. Here, this work reports a multimodal nanoplatform with a reactive oxygen species (ROS) cascade for gas therapy/ferroptosis/chemotherapy in reversing MDR. The nanoplatform disassembles when responding to intracellular ROS and exerts three main functions: First, nitric oxide (NO) targeted delivery can reverse MDR by downregulating P-gp expression and inhibiting mitochondrial function. Second, ferrocene-induced ferroptosis breaks the redox balance in the tumor intracellular microenvironment and synergistically acts against the tumor. Third, the release of paclitaxel (PTX) is precisely controlled in situ in the tumor for chemotherapy that avoids damage to normal tissues. Excitingly, this multimodal nanoplatform is a promising weapon for reversing MDR and may provide a pioneering paradigm for synergetic cancer therapy.

Maize residue retention shapes soil microbial communities and co-occurrence networks upon freeze-thawing cycles.

Maize residue retention is an effective agricultural practice for improving soil fertility in black soil region, where suffered from long freezing-thawing periods and intense freeze-thawing (FT) cycles. However, very few studies have examined the influence of maize residue retention on soil microbial communities under FT cycles. We investigated the response of soil microbial communities and co-occurrence networks to maize residue retention at different FT intensities over 12 cycles using a microcosm experiment conditioned in a temperature incubator. Our results indicated that maize residue retention induced dramatic shifts in soil archaeal, bacterial and fungal communities towards copiotroph-dominated communities. Maize residue retention consistently reduced soil fungal richness across all cycles, but this effect was weaker for archaea and bacteria. Normalized stochastic ratio analysis revealed that maize residue retention significantly enhanced the deterministic process of archaeal, bacterial and fungal communities. Although FT intensity significantly impacted soil respiration, it did not induce profound changes in soil microbial diversity and community composition. Co-occurrence network analysis revealed that maize residue retention simplified prokaryotic network, while did not impact fungal network complexity. The network robustness index suggested that maize residue retention enhanced the fungal network stability, but reduced prokaryotic network stability. Moreover, the fungal network in severe FT treatment harbored the most abundant keystone taxa, mainly being cold-adapted fungi. By identifying modules in networks, we observed that prokaryotic Module #1 and fungal Module #3 were enhanced by maize residue retention and contributed greatly to soil quality. Together, our results showed that maize residue retention exerted stronger influence on soil microbial communities and co-occurrence network patterns than FT intensity and highlighted the potential of microbial interactions in improving soil functionality.

TRIB3 promotes the progression of renal cell carcinoma by upregulating the lipid droplet-associated protein PLIN2.

Abnormal lipid metabolism and lipid accumulation are characteristic hallmarks of renal cell carcinoma (RCC). While there is prior evidence closely linking such lipid accumulation within RCC cells and consequent tumorigenesis, the mechanisms underlying this process remain incompletely understood. In this study, a series of bioinformatics analyses were initially performed by screening RCC databases and gene sets, ultimately leading to the identification of TRIB3 as an oncogene that functions as a central regulator of lipid metabolism. TRIB3 overexpression was observed in both RCC patient tumor tissues and cell lines, and this upregulation was correlated with a worse RCC patient prognosis. When TRIB3 was knocked down, this resulted in a reduction in lipid accumulation and the consequent induction of endoplasmic reticulum (ER) stress-related apoptotic cell death. At the molecular level, interactions between TRIB3 and PLIN2 were found to abrogate TEB4-mediated PLIN2 ubiquitination and consequent degradation, thus maintaining higher PLIN2 expression levels. This simultaneously helps facilitate the accumulation of lipids while preserving ER homeostasis, thus driving accelerated RCC tumor progression. This TRIB3-PLIN2 axis thus represents a promising new target for efforts to treat RCC.

ROS-driven supramolecular nanoparticles exhibiting efficient drug delivery for chemo/Chemodynamic combination therapy for Cancer treatment.

Drug-based supramolecular self-assembling delivery systems have enhanced the bioavailability of chemotherapeutic drugs and reduced systemic side effects; however, improving the delivery efficiency and responsive release ability of these systems remains challenging. This study focuses primarily on the utilization of per-6-thio-ß-cyclodextrin (CD) to link a significant quantity of paclitaxel (PTX) via ROS-sensitive thioketal (TK) linkages (designated as CDTP), thereby allowing efficiently drug release when exposed to high levels of reactive oxygen species (ROS) in the tumor microenvironment. To construct these supramolecular nanoparticles (NPs) with CDTP, we introduced PEGylated ferrocene (Fc) through host-guest interactions. The intracellular hydrogen peroxide (H2O2) is converted into hydroxyl radicals (•OH) through the Fc-catalyzed Fenton reaction. Additionally, the generated Fc+ consumes the antioxidant glutathione (GSH). In both in vivo and in vitro experiments, CDTP@Fc-PEG NPs were absorbed effectively by tumor cells, which increased levels of ROS and decreased levels of GSH, disrupting the redox balance of cancer cells and increasing their sensitivity to chemotherapy. Furthermore, CDTP@Fc-PEG NPs exhibited high tumor accumulation and cytotoxicity without causing significant toxicity to healthy organs. Collectively, our results suggest CDTP@Fc-PEG NPs as a promising supramolecular nano-delivery platform for high drug-loading of PTX and synergistic chemotherapy.

Core bacteria and fungi in response to residue retention and their contribution to soil multifunctionality in maize agroecosystem.

Core microbiome has been proven to play crucial roles in soil function. However, we still lack knowledge on how core microbiome responds to crop residue retention, and whether they contribute to this process. Consequently, we examined the effect of residue retention on soil core and non-core microbial communities in maize seedling, mature stage and freezing period based on a multi-site field experiment in Sanjiang Plain, Northeast China. Totally, 247 bacterial amplicon sequence variants (ASVs) and 109 fungal ASVs were identified as core microbiota. Both core and non-core bacterial/fungal community composition were significantly influenced by residue retention across all study sites. Especially, the core fungal community shifted towards a saprotroph-dominated community. Normalized stochastic ratio pattern revealed that that deterministic process dominated both core and non-core microbial community assembly processes. Residue retention enhanced the deterministic process of core microbial community assembly, while exhibited opposite effect on non-core microbial community. This study also revealed that soil fungi were more sensitive to residue retention than bacteria, with a larger proportion of core fungi were enriched or depleted by residue retention. In addition, residue retention complicated core bacterial co-occurrence network, while simplified fungal network. Our results pointed out both no reduction in microbial diversity or collapse in microbial network structure after repeated freezing-thawing cycles. The potential function of core microbiome was evaluated through random forest analysis and structural equation model, the results indicated core microbiome contributed more to multifunctionality than non-core microbiome. Overall, this study strengthened our understanding of soil core microbiome in response to residue retention, and highlighted their importance in maintaining soil multifunctionality.

Tillage Practices and Residue Management Manipulate Soil Bacterial and Fungal Communities and Networks in Maize Agroecosystems.

Tillage practices and residue management are highly important agricultural practices. However, very few studies have examined the influence of tillage practices and residue management on both bacterial and fungal communities and network patterns in consecutive years. We examined the effects of different tillage practices, including no tillage, rotary tillage, and deep tillage, on soil bacterial and fungal communities and co-occurrence networks following residue removal and residue retention in 2017 and 2018. This study showed that both bacterial and fungal communities were unaffected by tillage practices in 2017, but they were significantly impacted in 2018. Soil fungal operational taxonomic unit (OTU) richness was significantly enhanced by deep tillage compared with no tillage in 2018, while bacterial OTU richness was unaffected in either year. Tillage practices had differing effects on soil microbial co-occurrence networks, with rotary and deep tillage increasing the complexity of bacterial networks but simplifying fungal networks. However, residue retention only induced a shift in the fungal community and simplified soil bacterial and fungal networks in 2018. This study highlights the dissimilar responses of bacterial and fungal networks to tillage practices and emphasizes that tillage practice is more important than residue management in shaping soil microbial communities.

Vertical and temporal variations of soil bacterial and archaeal communities in wheat-soybean rotation agroecosystem.

Soil microbes are an essential component of terrestrial ecosystems and drive many biogeochemical processes throughout the soil profile. Prior field studies mainly focused on the vertical patterns of soil microbial communities, meaning their temporal dynamics have been largely neglected. In the present study, we investigated the vertical and temporal patterns of soil bacterial and archaeal communities in a wheat-soybean rotation agroecosystem at a depth of millions of sequences per sample. Our results revealed different vertical bacterial and archaeal richness patterns: bacterial richness was lowest in the deep soil layer and peaked in the surface or middle soil layer. In contrast, archaeal richness did not differ among soil layers. PERMANOVA analysis indicated that both bacterial and archaeal community compositions were significantly impacted by soil depth but unaffected by sampling time. Notably, the proportion of rare bacteria gradually decreased along with the soil profile. The rare bacterial community composition was the most important indicator for soil nutrient fertility index, as determined by random forest analysis. The soil prokaryotic co-occurrence networks of the surface and middle soil layers are more connected and harbored fewer negative links than that of the deep soil layer. Overall, our results highlighted soil depth as a more important determinant than temporal variation in shaping the soil prokaryotic community and interspecific interactions and revealed a potential role of rare taxa in soil biogeochemical function.

Circular RNA circVAMP3 promotes aerobic glycolysis and proliferation by regulating LDHA in renal cell carcinoma.

Metabolic dysfunction is seen in cancer cells where increased glycolysis provides energy for growth. Circular RNAs (circRNAs) are thought to assist in glucose metabolism and the switch to glycolysis. Through screening, we found that circVAMP3 was necessary for both glycolytic and proliferative activities in renal cell carcinoma (RCC). Furthermore, circVAMP3 expression was elevated in RCC patients in correspondence with TNM stage. Mechanistically, circVAMP3 was observed to interact directly with lactate dehydrogenase A (LDHA) and modulate its activity. The circVAMP3-LDHA interaction facilitated LDHA phosphorylation at tyrosine 10 (Y10) catalyzed by the upstream kinase fibroblast growth factor receptor type 1 (FGFR1). Therefore, this study reveals a novel molecular mechanism by which circVAMP3 promotes glycolysis and proliferation through regulating the enzymatic activity of glycolytic enzyme, suggesting that circVAMP3 may represent an RCC biomarker and treatment target.

Smart dual responsive nanocarriers with reactive oxygen species amplification assisted synergistic chemotherapy against prostate cancer.

Conventional chemotherapy efficacy is impeded by poor water solubility, inferior tissue targeting, and severe systemic toxic effect. Synergistic chemotherapy has become prominent with the stimulus-response drug delivery system (DDS) to treat solid malignancies. The most popularly employed responsive stimulus is reactive oxygen species (ROS), which is proven to primarily sensitize chemotherapy and enhance antitumor impact. In this study, we have successfully developed smart dual responsive nanocarriers with ROS self-amplification, particularly responding to disassemble under the high levels of ROS and esterase in the tumor microenvironment (TME) and to release docetaxel (DTX) efficiently. Additionally, we utilized palmitoyl ascorbate (PA) as a stabilizer by taking advantage of its amphiphilic structure. PA is also an excellent ROS generator that produces a large amount of hydrogen peroxide (H2O2) in TME to achieve ROS self-amplification. Also, elevated levels of ROS could continue to activate ROS-sensitive thioketal and make the remaining nanocarriers disassemble for sustaining the release of chemotherapeutics, realizing a positive feedback loop for ROS generation and ROS amplification, as well as sensitizing chemotherapy efficacy. The smart dual responsive nanocarriers may serve as a promising and prospective strategy for treating prostate cancer and promoting synergistic cancer therapy.

Cyclodextrin-based supramolecular nanoparticles break the redox balance in chemodynamic therapy-enhanced chemotherapy.

Drug delivery based on abnormal features of the tumor microenvironment (TME) has attracted considerable interest worldwide. In this study, we proposed an applicable strategy to increase the reactive oxygen species (ROS) and inhibit glutathione (GSH), in an effort to amplify oxidative damage in prostate cancer cells. Specifically, we developed dual-responsive supramolecular self-assembled nanoparticles (NPs) based on polymerized methacrylic acid (MA) and polymerized poly(ethylene glycol) dimethyl acrylate-modified ß-cyclodextrin (CD) with ferrocene (Fc)-connected (S) (+)-camptothecin (CPT) (designated as MA-CD/Fc-CPT NPs). The as-prepared negatively charged supramolecular NPs can be taken up by tumor cells successfully owing to their reversible negative-to-positive charge transition capacity at acidic pH. The supramolecular NPs increased ROS generation and decreased GSH to amplify oxidative stress and improve the therapeutic effect of chemotherapy. As expected, MA-CD/Fc-CPT NPs displayed good drug delivery capabilities to tumor cells or tissues. MA-CD/Fc-CPT NPs also inhibited cancer cell proliferation in both the cells and tissues. This result was partially due to increased ROS generation and decreased GSH, which contributed to more pronounced oxidative stress. The as-prepared supramolecular NPs displayed great biosafety to normal tissues. According to our results, negatively charged supramolecular MA-CD/Fc-CPT NPs are well-suited for drug delivery and improved cancer treatment in TMEs.

Effective Sonosensitizer Delivery by Redox Sensitive Nanoparticles for Prostate Cancer Sonodynamic Therapy via Amplifying Oxidative Stress and Peroxidation.

Sonodynamic therapy (SDT), a novel noninvasive therapeutic modality, provides many noteworthy benefits by generating reactive oxygen species (ROS). However, water-insoluble sonosensitizer delivery strategies have continuously underperformed because of unavoidable toxicity and a short circulation time. In this study, l-cystine derivative-based biocompatible nanoparticles (NPs) that can be used in SDT and induce limited cytotoxicity are designed and synthesized. After ultrasonic (US) irradiation, these sonosensitizer-loaded NPs show highly efficient sonodynamic performance that leads to cytotoxic ROS production. The ability to stop and start ROS generation induced by US irradiation enables accurate temporal and spatial control. In vivo and in vitro experiments are systematically performed to investigate the effects of this system on tumors, and the results indicate remarkable tumor suppression via markedly high persistent oxidative stress that induces peroxidation and endoplasmic reticulum stress. Thus, this novel temporally and spatially controllable ROS generation platform offers a safe and effective theranostic strategy for prostate cancer treatment.

Disentangling the role of salinity-sodicity in shaping soil microbiome along a natural saline-sodic gradient.

Increasing salinity and sodicity have been recognized as threats to soil fertility and crop yield worldwide. In recent years, salt-affected soils have received great attentions due to the shortage of arable land. This study therefore aims to characterize soil bacterial community, assembly process and co-occurrence network along natural saline-sodic gradients across Songnen Plain, Northeast China. As revealed by Miseq sequencing, 8482 bacterial OTUs were annotated at 97% identity across 120 soil samples. Our results indicated that soil salinity-sodicity not only significantly decreased bacterial richness and but also impacted bacterial community composition. The dominant bacterial phyla included Proteobacteria (28.89%), Actinobacteria (19.96%) and Gemmatimonadetes (16.71%). By applying threshold indicator species analysis (TITAN), OTUs from Gemmatimonadetes were found to be the taxa with the most prevalent and strongest preference for high salinity-sodicity. Null model analysis revealed that the majority (76.4%) of ßNTI values were below -2 or above 2, indicating deterministic process was dominant across all samples. Notably, deterministic process contributed to a greater extent in higher saline-sodic soils. The bacterial co-occurrence network was more complex in slightly saline-sodic soils than in moderately and extremely saline-sodic soils, reflected by more nodes, more hubs and stronger connections, which was mainly driven by soil pH. These results provide strong evidence that salinity-sodicity was a key determinant in shaping soil bacterial community, assembly process and co-occurrence network pattern.

Dual pH- and Glutathione-Responsive CO2-Generating Nanodrug Delivery System for Contrast-Enhanced Ultrasonography and Therapy of Prostate Cancer.

Ultrasonography (US) contrast imaging using US contrast agents has been widely applied for the diagnosis and differential diagnosis of tumors. Commercial US contrast agents have limited applications because of their large size and shorter imaging time. At the same time, the desired therapeutic purpose cannot be achieved by applying only conventional US contrast agents. The development of nanoscale US agents with US imaging and therapeutic functions has attracted increasing attention. In this study, we successfully developed DOX-loaded poly-1,6-hexanedithiol-sodium bicarbonate nanoparticles (DOX@HADT-SS-NaHCO3 NPs) with pH-responsive NaHCO3 and GSH-responsive disulfide linkages. DOX@HADT-SS-NaHCO3 NPs underwent acid-triggered decomposition of NaHCO3 to generate CO2 bubbles and a reduction of disulfide linkages to further promote the release of CO2 and DOX. The potential of DOX@HADT-SS-NaHCO3 NPs for contrast-enhanced US imaging and therapy of prostate cancer was thoroughly evaluated using in vitro agarose gel phantoms and a C4-2 tumor-bearing nude mice model. These polymeric NPs displayed significantly enhanced US contrast at acidic pH and antitumor efficacy. Therefore, the NaHCO3 and DOX-encapsulated polymeric NPs hold tremendous potential for effective US imaging and therapy of prostate cancer.

A Meta-Analysis of Glasgow Prognostic Score and Modified Glasgow Prognostic Score as Biomarkers for Predicting Survival Outcome in Renal Cell Carcinoma.

Purpose: Accumulative studies suggest the Glasgow prognostic score (GPS) and modified Glasgow prognostic score (mGPS) to be potential biomarkers; however, their prognostic value remains debatable. Our meta-analysis focused on assessing the accurate prognostic value of GPS and mGPS in patients with renal cell carcinoma (RCC) in addition to their effectiveness. Methods: To investigate the relationship between mGPS/GPS and prognostic value in patients with RCC, we performed a comprehensive retrieval of relevant articles from databases such as PubMed, Embase, Web of Science, and Medline up to February 1, 2020. STATA 15.0 software was used to obtain pooled hazard ratios (HRs) and their 95% confidence intervals for survival outcome, including overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS). A formal meta-analysis of these outcomes was performed. Results: In total, 2,691 patients with RCC were enrolled from 15 cohort studies. Higher GPS/mGPS (GPS/mGPS of 2) indicated poorer OS, CSS, PFS, and RFS in patients with RCC. Similarly, medium GPS/mGPS (GPS/mGPS of 1) also had a significant association with poorer OS, CSS, PFS, and RFS but superior than higher GPS/mGPS in these patients. Conclusion: GPS and mGPS are effective biomarkers for predicting prognosis in patients with RCC, and higher GPS and mGPS are closely related to inferior survival outcomes. More randomized controlled trials are needed to investigate the promising value of GPS/mGPS in the future.