The significant contribution of comammox bacteria to nitrification in a constructed wetland revealed by DNA-based stable isotope probing.

The discovery of Comammox bacteria (CMX) has changed our traditional concept towards nitrification, yet its role in constructed wetlands (CWs) remains unclear. This study investigated the contributions of CMX and two canonical ammonia-oxidizing microorganisms, ammonia-oxidizing bacteria (AOB) and archaea to nitrification in four regions (sediment, shoreside, adjacent soil, and water) of a typical CW using DNA-based stable isotope probing. The results revealed that CMX not only widely occurred in sediment and shoreside zones with high abundance (5.08 × 104 and 6.57 × 104 copies g-1 soil, respectively), but also actively participated in ammonia oxidation, achieving ammonia oxidation rates of 1.43 and 2.00 times that of AOB in sediment and shoreside, respectively. Phylogenetic analysis indicated that N. nitrosa was the dominant and active CMX species. These findings uncovered the crucial role of CMX in nitrification of sediment and shoreside, providing a new insight into nitrogen cycle of constructed wetlands.

Frozen inactivated autograft replantation for bone and soft tissue sarcomas.

Background: The frozen inactivation of autologous tumor bones using liquid nitrogen is an important surgical method for limb salvage in patients with sarcoma. At present, there are few research reports related to frozen inactivated autograft replantation. Methods: In this study, we retrospectively collected the clinical data of patients with bone and soft tissue sarcoma treated with liquid nitrogen-frozen inactivated tumor bone replantation, and analyzed the safety and efficacy of this surgical method. The healing status of the frozen inactivated autografts was evaluated using the International Society of Limb Salvage (ISOLS) scoring system. Functional status of patients was assessed using the Musculoskeletal Tumor Society (MSTS) scale. Results: This study included 43 patients. The average length of the bone defect after tumor resection is 16.9 cm (range 6.3-35.3 cm). Patients with autograft not including the knee joint surface had significantly better healing outcomes (ISOLS scores) (80.6% ± 15% vs 28.2% ± 4.9%, P<0.001) and limb function (MSTS score) (87% ± 11.6% vs 27.2% ± 4.4%, P<0.001) than patients with autografts including the knee joint surface. The healing time of the end of inactivated autografts near the metaphyseal was significantly shorter than that of the end far away from the metaphyseal (9.8 ± 6.3 months vs 14.9 ± 6.3 months, P=0.0149). One patient had local recurrence, one had an autograft infection, five (all of whom had an autograft including the knee joint surface) had joint deformities, and seven had bone non-union. Conclusion: Frozen inactivated autologous tumor bone replantation is safe and results in good bone healing. But this method is not suitable for patients with autograft involving the knee joint surface.

Combining nanoparticle albumin-bound paclitaxel with camrelizumab in advanced soft tissue sarcoma: activity, safety, and future perspectives.

Background: It is still uncertain whether Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor have synergistic effects on metastatic soft tissue sarcomas (STSs). The purpose of this study was to evaluate the safety and activity of nab-paclitaxel plus camrelizumab (a PD-1 inhibitor) in patients with advanced STS who had previously failed chemotherapy. Methods: In this single-center, open-label, single-arm phase II clinical trial, patients with advanced (unresectable or metastatic) STS who had previously failed chemotherapy received up to six cycles of nab-paclitaxel plus camrelizumab, whereas camrelizumab treatment was continued for up to 1 year. The median progression-free survival (PFS), objective response rate (ORR) and safety were collected and evaluated. Results: This trial included 40 patients (28 men and 12 women). The overall ORR was 22.5%, and the median PFS was 1.65 months (95% confidence interval [CI], 1.3-2.0 months). Patients with epithelioid sarcoma demonstrated a longer PFS compared with those with other histological subtypes (2.3 months vs. 1.5 months, respectively); however, this difference was not significant. Patients who had received only one line of previous chemotherapy had a significantly longer PFS compared with those who had undergone two or more lines of previous chemotherapy (2.8 months vs. 1.3 months, respectively, p = 0.046). In terms of safety, the toxicity of this combination therapy is mild and no serious adverse events have occurred. Conclusion: Nab-paclitaxel plus camrelizumab exhibited modest activity and mild toxicity in treating epithelioid sarcoma, angiosarcoma, and fibrosarcoma. The overall effectiveness of this treatment regimen for advanced STS is relatively low. Further research on combining nab-paclitaxel with effective drugs, including chemotherapy and targeted agents, for these specific STS subtypes is needed.

Inactivation and replantation of the knee joint: an infeasible surgical method.

BACKGROUND: The inactivation and replantation of autologous tumor bones are important surgical methods for limb salvage in patients with malignancies. Currently, there are few reports on the inactivation and replantation of the knee joint. In this study, we aimed to evaluate the feasibility of our surgical approach. METHODS: This is a retrospective case series study. We retrospectively collected the clinical data of patients with sarcoma treated with knee joint inactivation and replantation and analyzed the efficacy of this surgical method. The bone healing and complications in these patients after inactivated autograft replantation were assessed. RESULTS: This study included 16 patients. Fifteen patients had osteosarcoma, and one had Ewing's sarcoma. The average length of the inactivated bone is 20.2 cm (range 13.5-25.3 cm). All the patients underwent internal plate fixation. The average follow-up duration was 30 months (range 8-60 months). Before the data deadline of this study, eight (50%) patients were still alive, and eight (50%) died of sarcoma metastasis. Eight (50%) patients achieved bone healing at the diaphysis site of the inactivated tumor bone, with an average bone healing time of 21.9 months (range, 12-36 months). Five (31%) patients died due to metastases and did not achieve bone healing. Two (12.5%) patients did not achieve bone healing because of infection, and one (6.3%) patient underwent amputation due to tumor recurrence. Ten (62.5%) patients experienced fractures around the joint ends of the inactivated replanted bone, and eight of these ten patients were combined with joint dislocation. CONCLUSION: The incidence of joint deformities after the knee-joint inactivation and replantation is extremely high and is not recommended for use.

Apatinib plus chemotherapy for non-metastatic osteosarcoma: a retrospective cohort study.

Background: Effective adjuvant therapy for osteosarcoma is necessary for improved outcomes. Previous studies demonstrated that apatinib plus doxorubicin-based chemotherapy may improve the efficacy of neoadjuvant therapy. This study aimed to clarify the effectiveness and safety of apatinib plus doxorubicin and cisplatin (AP) as neoadjuvant therapy for osteosarcoma. Methods: The clinical data of osteosarcoma patients who underwent neoadjuvant therapy and surgery between August 2016 and April 2022 were retrospectively collected and analyzed. Patients were divided into two groups: the apatinib plus AP (apatinib + AP) group and the methotrexate, doxorubicin, and cisplatin (MAP) group. Results: This study included 42 patients with nonmetastatic osteosarcoma (19 and 23 patients in the apatinib + AP and MAP groups, respectively). The 1- and 2-year disease-free survival rates in the apatinib + AP group were higher than those in the MAP group, but the difference was not significant (P=0.165 and 0.283, respectively). Some adverse events were significantly more common in the apatinib + AP group than in the MAP group, including oral mucositis (grades 3 and 4) (52.6% vs. 17.4%, respectively, P=0.023), limb edema (47.4% vs. 17.4%, respectively, P=0.049), hand-foot syndrome (31.6% vs. 0%, respectively, P=0.005), proteinuria (26.3% vs. 0%, respectively, P=0.014), hypertension (21.1% vs. 0%, respectively, P=0.035), and hypothyroidism (21.1% vs. 0%, respectively, P=0.035). No drug-related deaths occurred. There was no statistically significant difference in the incidence of postoperative complications between the groups (P>0.05). Conclusion: The present study suggests that apatinib + AP may be a promising candidate for neoadjuvant therapy for osteosarcoma, warranting further validation in prospective randomized controlled clinical trials with long-term follow-up.

Argon-helium knife cryoablation plus programmed cell death protein 1 inhibitor in the treatment of advanced soft tissue sarcomas: there is no evidence of the synergistic effects of this combination therapy.

Background: Effective treatment for advanced soft tissue sarcomas (STSs) is necessary for improved outcomes. Previous studies have suggested that cryoablation can have a synergistic effect with programmed cell death protein-1 (PD-1) inhibitor in the treatment of malignancy. This study aimed to clarify the efficacy and safety of argon-helium knife cryoablation in combination with PD-1 inhibitor in the treatment of STSs. Methods: Retrospectively collected and analyzed the clinical data of patients with advanced STS who underwent cryoablation and PD-1 inhibitor between March 2018 and December 2021. Results: This study included 27 patients with advanced STS. In terms of target lesions treated with cryoablation, 1 patient achieved complete response, 15 patients had partial response (PR), 10 patients had stable disease, and 1 patient had progressive disease. This corresponded to an overall response rate of 59.3% and a disease control rate of 96.3%. In terms of distant target lesions untreated with cryoablation, only two patients had a PR compared to the diameter of the lesion before ablation. The combination therapy was relatively well tolerated. None of the patients experienced treatment-related death or delayed treatment due to adverse events. Conclusion: Cryoablation combined with PD-1 inhibitors in the therapy of advanced STS is safe and can effectively shrink the cryoablation-target lesion. However, there is no evidence of the synergistic effects of this combination therapy.

Development and Validation of CXCR4 Nomogram-Based Immune Infiltration/Tumor Inflammation in Primary Glioblastoma.

Glioblastoma (GBM) is a highly malignant and aggressive tumor with poor prognosis. Therefore, the discovery of new prognostic molecular markers is of great significance for clinical prognosis. The CXC chemokine receptor (CXCR) members play a key regulatory role in many cancers. In this study, we explore the clinical value and application of the CXCR members in primary glioblastoma. Two GBM datasets from The Cancer Genome Atlas (TCGA) and The China Glioma Genome Atlas (CGGA) databases were used to explore the relationship between differential expression of CXCRs and GBM subtypes as well as immune infiltration. C-X-C motif chemokine receptor 4 (CXCR4) was screened as an independent prognostic factor, and a nomogram and risk prediction model were developed and tested in the CGGA database using the TCGA database. Receiver operating curve (ROC) and decision curve analysis (DCA) found good accuracy and net benefit of the models. The correlation of CXCR4 with immune infiltration and tumor was analyzed using CancerSEA and TIMER. In in vitro experiments, we found that CXCR4 was significantly overexpressed in glioblastoma and was closely related to the inflammatory response of U251/U87 cells. CXCR4 is an excellent independent prognostic factor for glioblastoma and positively correlates with tumor inflammation.

Chemotherapeutic drugs for soft tissue sarcomas: a review.

Despite the low incidence of soft tissue sarcomas (STSs), hundreds of thousands of new STS cases are diagnosed annually worldwide, and approximately half of them eventually progress to advanced stages. Currently, chemotherapy is the first-line treatment for advanced STSs. There are difficulties in selecting appropriate drugs for multiline chemotherapy, or for combination treatment of different STS histological subtypes. In this study, we first comprehensively reviewed the efficacy of various chemotherapeutic drugs in the treatment of STSs, and then described the current status of sensitive drugs for different STS subtypes. anthracyclines are the most important systemic treatment for advanced STSs. Ifosfamide, trabectedin, gemcitabine, taxanes, dacarbazine, and eribulin exhibit certain activities in STSs. Vinca alkaloid agents (vindesine, vinblastine, vinorelbine, vincristine) have important therapeutic effects in specific STS subtypes, such as rhabdomyosarcoma and Ewing sarcoma family tumors, whereas their activity in other subtypes is weak. Other chemotherapeutic drugs (methotrexate, cisplatin, etoposide, pemetrexed) have weak efficacy in STSs and are rarely used. It is necessary to select specific second- or above-line chemotherapeutic drugs depending on the histological subtype. This review aims to provide a reference for the selection of chemotherapeutic drugs for multi-line therapy for patients with advanced STSs who have an increasingly long survival.

Immunotherapy Plus Radiotherapy for the Treatment of Sarcomas: Is There a Potential for Synergism?

Soft tissue sarcoma (STS) is a highly heterogeneous malignant tumor derived from mesenchymal tissue. Advanced STS has a poor response to the current anti-cancer therapeutic options, with a median overall survival of less than two years. Thus, new and more effective treatment methods for STS are needed. Increasing evidence has shown that immunotherapy and radiotherapy have synergistic therapeutic effects against malignant tumors. In addition, immunoradiotherapy has yielded positive results in clinical trials for various cancers. In this review, we discuss the synergistic mechanism of immunoradiotherapy in cancer treatment and the application of this combined regimen for the treatment of several cancers. In addition, we summarize the existing evidence on the use of immunoradiotherapy for the treatment of STS and the relevant clinical trials that are currently ongoing. Furthermore, we identify challenges in the use of immunoradiotherapy for the treatment of sarcomas and propose methods and precautions for overcoming these challenges. Lastly, we propose clinical research strategies and future research directions to help in the research and treatment of STS.

COPS3 inhibition promotes cell proliferation blockage and anoikis via regulating PFKFB3 in osteosarcoma cancer cells.

As a key component of the COP9 signalosome complex, which participates in a variety of physiological processes, COPS3 is intimately related to multiple cancers. It promotes cell proliferation, progression and metastasis in several cancer cells. However, whether COPS3 participates in regulating anoikis, a specific kind of apoptosis and functions as an essential modulator of cell metastasis, has not yet been studied. Here, we found COPS3 is highly expressed in several cancers especially in osteosarcoma (OS). Overexpression of COPS3 promoted cell proliferation, cell viability and migration/invasion in both control cells and oxaliplatin (Oxa) treated cells. On the contrary, knockdown of COPS3 further enhanced the cytotoxicity of Oxa. Utilizing bioinformatics analysis, we found that COPS3 was higher expressed in the metastatic group, and associated with the extra-cellular matrix (ECM) receptor interaction pathway, which involve in regulating anoikis. In an anoikis model, COPS3 expression varied and genetic modification of COPS3 influenced the cell death enhanced by Oxa. PFKFB3, an essential modulator of glycolysis, was found to interact with COPS3. Inhibition of PFKFB3 promoted apoptosis and anoikis enhanced by Oxa, and COPS3 overexpression failed to rescue this cell death. On the contrary, in the COPS3 knockdown cells, overexpression of PFKFB3 recovered the anoikis resistance, indicating COPS3 function upstream of PFKFB3. In summary, our results elucidated that COPS3 modulated anoikis via affecting PFKFB3 in OS cancer cells.

Ubiquitous occurrence and functional dominance of comammox Nitrospira in full-scale wastewater treatment plants.

The recent discovery of complete ammonia oxidation (comammox) bacteria has fundamentally upended the traditional two-step nitrification conception, but their functional importance in wastewater treatment plants (WWTPs) is still poorly understood. This study investigated distributions of comammox Nitrospira, ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in activated sludge samples collected from 25 full-scale WWTPs. Using quantitative PCR (qPCR) and 16S rRNA gene amplicon sequencing, our results revealed that comammox Nitrospira ubiquitously occurred in all of 25 WWTPs and even outnumbered AOB and AOA with an average abundance of 1∼183 orders of magnitude higher in 19 WWTPs. Moreover, DNA-based stable isotope probing (DNA-SIP) assays validated that comammox Nitrospira actively participated in ammonia oxidation in the three microcosms seeding with activated sludge from three typical WWTPs, in which the ratios of comammox amoA to AOB amoA were at the range of 1∼10, 10∼100 and >100, respectively. Phylogenetic analysis in heavy fractions further indicated that Nitrospira nitrosa (N. nitrosa) was the dominant and active species. We quantified the contribution of ammonia oxidizers based on the currently available kinetic parameters of the representative species and found that comammox made major contributions to ammonia oxidation than other nitrifiers (5 ∼ 106 times that of AOB). The findings not only demonstrate the ubiquitous occurrence of comammox, but also highlight their functional dominance in ammonia oxidation in WWTPs.

Efficacy and safety of sintilimab plus doxorubicin in advanced soft tissue sarcoma: A single-arm, phase II trial.

Background: Chemoimmunotherapy is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this combination treatment in patients with metastatic soft tissue sarcoma (STS) are currently limited. This study evaluated the safety and efficacy of a programmed cell death protein 1 (PD-1) inhibitor plus doxorubicin in patients with advanced STS who failed previous systemic therapy. Methods: This was a single-center, single-arm, open-label phase II trial. Patients with unresectable or metastatic STS who had previously failed systemic therapy were enrolled. Patients received up to six cycles of doxorubicin and sintilimab (a PD-1 inhibitor), while sintilimab treatment continued for up to 2 years. Primary outcomes were objective response rate (ORR) and safety. Univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and progression-free survival (PFS). Results: A total of 38 patients (20 men and 18 women) were enrolled in this study. The overall ORR was 39.5%, disease control rate was 71.1%, and the median PFS was 4.5 months [95% confidence interval (CI), 3.0-8.5 months]. The adverse events (AEs) associated with the combined treatment were mild, manageable, and well-tolerated. The most common grade 3 or higher AEs were hematologic, including leukopenia (21.1%), anemia (18.4%), and thrombocytopenia (18.4%). Patients with undifferentiated pleomorphic sarcoma (UPS) or dedifferentiated liposarcoma had a significantly longer PFS than those with other pathological subtypes [hazard ratio (HR) = 0.42, 95% CI 0.21-0.83; p = 0.013]. There was no significant difference in the median PFS between patients who had previously received anthracycline-based chemotherapy and those who had not (HR = 0.74, 95% CI 0.34-1.58, p = 0.43). Conclusion: Sintilimab plus doxorubicin is a safe and promising treatment for patients with advanced STS who have failed previous systemic therapy (including anthracycline-based chemotherapy). The efficacy of this combination therapy in UPS and dedifferentiated liposarcoma is superior to that in other sarcomas. Clinical Trial Registration: https://www.chictr.org.cn, registration number: ChiCTR1900027009.

PD-1/L1 inhibitor plus chemotherapy in the treatment of sarcomas.

There is an urgent clinical need for new therapeutic regimens for the effective treatment of advanced sarcomas. Accumulating evidence suggests that programmed death receptor-1/programmed death protein ligand-1 (PD-1/L1) inhibitors have synergistic effects with chemotherapy and have been approved for treatment of lung cancer, gastroesophageal cancer, and breast cancer. In this review, we reviewed the synergistic mechanism of PD-1/L1 inhibitors plus chemotherapy in the treatment of cancers, and the application of this combined regimen in several cancers, followed by a summary of the current evidence on the application of this combined regimen in the treatment of sarcomas as well as the main clinical trials currently underway. Based on the findings of this review, we believe that this combined approach will play an important role in the treatment of some subtypes of sarcomas in the future.

Comammox bacteria predominate among ammonia-oxidizing microorganisms in municipal but not in refinery wastewater treatment plants.

Comammox bacteria have proved to be one dominant and significant ammonia-oxidizing microorganisms (AOMs) in municipal wastewater treatment plants (WWTPs), however, it still remains unknown about their abundance and diversity in industrial WWTPs. In this study, activated sludge samples from 8 municipal WWTPs and 6 industrial WWTPs treating refinery wastewater were taken and analyzed using qPCR and amoA gene sequencing. Intriguingly, quantitative real-time PCR (qPCR) results suggested that comammox bacteria had a higher numerical abundance compared with ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in municipal WWTPs but did not in refinery WWTPs. Moreover, comammox amoA sequences obtained from high-throughput sequencing were retrieved from all the 8 municipal samples but only 1 industrial sample. Further phylogenetic analysis revealed that N. nitrosa cluster accounted for as high as 79.56% of the total comammox affiliated sequences, which was the most numerically abundant comammox species in municipal WWTPs. This study provided new insights into the abundance and diversity of comammox bacteria in the biological nitrification process in municipal and refinery wastewater treatment systems.

Albumin-Bound Paclitaxel: Worthy of Further Study in Sarcomas.

Taxanes (paclitaxel and docetaxel) play an important role in the treatment of advanced sarcomas. Albumin-bound paclitaxel (nab-paclitaxel) is a new kind of taxane and has many advantages compared with paclitaxel and docetaxel. Nab-paclitaxel is currently approved for the treatment of advanced breast, non-small cell lung, and pancreatic cancers. However, the efficacy of nab-paclitaxel in sarcomas has not been reviewed. In this review, we first compare the similarities and differences among nab-paclitaxel, paclitaxel, and docetaxel and then summarize the efficacy of nab-paclitaxel against various non-sarcoma malignancies based on clinical trials with reported results. The efficacy and clinical research progress on nab-paclitaxel in sarcomas are also summarized. This review will serve as a good reference for the application of nab-paclitaxel in clinical sarcoma treatment studies and the design of clinical trials.

Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study.

BACKGROUND: There is increasing evidence that combination therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this treatment combination for patients with metastatic soft tissue sarcoma (STS) are currently limited. METHODS: The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan-Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant. RESULTS: A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8-3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018). CONCLUSION: Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.

Undifferentiated Pleomorphic Sarcoma with Neoplastic Fever: A Retrospective Study.

BACKGROUND: Although the annual incidence of undifferentiated pleomorphic sarcoma (UPS) is extremely low, it can be subdivided into different subtypes. UPS with fever of unknown origin (also known as neoplastic fever) is a specific subtype of UPS, which shows certain clinical features that differentiate it from other UPS subtypes. However, no studies have focused on this rare UPS subtype. This study retrospectively analyzed the clinical data of patients with UPS to provide a reference for the diagnosis and treatment of UPS with neoplastic fever. METHODS: This study included patients with UPS who were diagnosed and treated between June 2012 and June 2018. We examined whether these patients had a history of neoplastic fever. The characteristics of patients with UPS with neoplastic fever were summarized and analyzed. RESULTS: We reviewed the medical records of 183 patients with UPS. Seven (3.83%) of these patients had neoplastic fever. In patients with UPS with neoplastic fever, the primary lesions were located in the extremities and across the muscle space. In these patients, magnetic resonance imaging showed necrosis within the tumor body and extensive soft tissue edema around the tumor body. Patients with UPS with neoplastic fever had a lower metastasis rate (14.29% vs 44.94%) and a higher 3-year survival rate (85.71% vs 59.55%) than those without neoplastic fever. CONCLUSION: UPS with neoplastic fever is characterized by intratumoral necrosis and extensive edema of the surrounding soft tissues. Patients with UPS with neoplastic fever may have a better prognosis than those without neoplastic fever.

Efficacy and Response Biomarkers of Apatinib in the Treatment of Malignancies in China: A Review.

Apatinib is a multitarget tyrosine kinase inhibitor marketed in China for the treatment of advanced gastric cancer (GC) and hepatocellular carcinoma (HCC). It has also been used off-label for the treatment of many other malignancies. To comprehensively evaluate the efficacy of apatinib as a targeted therapy in the treatment of malignancies, we conducted systematic online and manual searches of the literature on apatinib in the treatment of malignancies. In this review, we first summarized the efficacy of apatinib against various malignancies based on clinical trials where results have been reported. In prospectively registered trials, apatinib has been proven to be effective against GC, HCC, lung cancer, breast cancer, sarcoma, esophageal cancer, colorectal cancer, ovarian cancer, cervical cancer, cholangiocarcinoma, diffuse large B-cell lymphoma, nasopharyngeal carcinoma, and differentiated thyroid cancer. The response biomarkers for apatinib were also reviewed. This review will serve as a good reference for the application of apatinib in clinical studies and the design of clinical trials.

Mitigating NO and N2O emissions from a pilot-scale oxidation ditch using bioaugmentation of immobilized aerobic denitrifying bacteria.

Nitrous oxide (N2O) emission from wastewater treatment plants (WWTPs) requires urgent mitigation because of its significant contribution to the greenhouse effect. In this study, bioaugmentation was applied in a pilot-scale oxidation ditch with the aerobic denitrifying bacteria strain PCN-1 immobilized on polyurethane biocarriers, which demonstrated effective N2O mitigation. Microbial community analysis suggested that the bioaugmentation facilitated a symbiotic relationship of the bacterial populations between the activated sludge and the biocarriers. The denitrifying bacteria with well-known N2O reducing capabilities predominated on the biocarriers. Correspondingly, the increases of denitrifying genes and NO and N2O reductase provided evidence for the enhanced genetic potential for NO and N2O reduction. Besides, the enriched comammox Nitrospira on the biocarriers is proposed as another significant driver for N2O mitigation by avoiding nitrite accumulation. In addition, the bioaugmentation enhanced the stability and recovery capability of the system in the ammonia overload and aeration failure shock tests.

Uranium bioremediation with U(VI)-reducing bacteria.

Uranium (U) pollution is an environmental hazard caused by the development of the nuclear industry. Microbial reduction of hexavalent uranium (U(VI)) to tetravalent uranium (U(IV)) reduces U solubility and mobility and has been proposed as an effective method to remediate uranium contamination. In this review, U(VI) remediation with respect to U(VI)-reducing bacteria, mechanisms, influencing factors, products, and reoxidation are systematically summarized. Reportedly, some metal- and sulfate-reducing bacteria possess excellent U(VI) reduction capability through mechanisms involving c-type cytochromes, extracellular pili, electron shuttle, or thioredoxin reduction. In situ remediation has been demonstrated as an ideal strategy for large-scale degradation of uranium contaminants than ex situ. However, U(VI) reduction efficiency can be affected by various factors, including pH, temperature, bicarbonate, electron donors, and coexisting metal ions. Furthermore, it is noteworthy that the reduction products could be reoxidized when exposed to oxygen and nitrate, inevitably compromising the remediation effects, especially for non-crystalline U(IV) with weak stability.