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The combined treatment systems have become a potential alternative to treat highly polluted industrial wastewater to achieve high-quality treated effluents. The current review focuses on the treatment systems compromising electrocoagulation (EC) as a pretreatment step followed by a biological treatment step. The reasons for applying EC as a pretreatment process were mainly to (1) detoxify the wastewater by removing inhibitors of the biotreatment step or (2) to remove the major part of the COD or (3) the dissolved materials that could cause fouling to membrane bioreactors or (4) to increase the activity of the microorganisms. This combination represents a new and promising application characterized by higher performance and removal efficiency. The main published findings related to this application are presented and analyzed. Besides, the statistical models used to optimize the process variables and the kinetics of microorganism growth rate are discussed herein. Most of the previous investigations were conducted in a laboratory-scale level with biologically treated water as a feed to the EC process. Only a few works applied a hybrid system consisting of the biological step and the EC step. In all studies, improved performance and higher removal efficiencies of the combined process were achieved particularly when applying aluminum electrodes, providing more than 95% removal efficiency. Many researchers have reported that they had faced a significant problem in the operation of the electrocoagulation process associated with the reduction of electrodes’ efficiency caused by deposits of the coagulation complex. This problem needs to be effectively resolved.

In the petroleum sector, the generation of oily sludge is an unavoidable byproduct, necessitating the development of efficient treatment strategies for both economic gain and the mitigation of negative environmental impacts. The intricate composition of oily sludge poses a formidable challenge, as existing treatment methodologies frequently fall short of achieving baseline disposal criteria. The processes of demulsification and dehydration are integral to diminishing the oil content and reclaiming valuable crude oil, thereby playing a critical role in the management of oily sludge. Among the myriad of treatment solutions, ultrasonic technology has emerged as a particularly effective physical method, celebrated for its diverse applications and lack of resultant secondary pollution. This comprehensive review delves into the underlying mechanisms and recent progress in the ultrasonic treatment of oily sludge, with a specific focus on its industrial implementations within China. Both isolated ultrasonic treatment and its combination with other technological approaches have proven successful in addressing oily sludge challenges. The adoption of industrial-scale systems that amalgamate ultrasound with multi-technological processes has shown marked enhancements in treatment efficacy. The fusion of ultrasonic technology with other cutting-edge methods holds considerable potential across a spectrum of applications. To fulfill the goals of resource recovery, reduction, and neutralization in oily sludge management, the industrial adoption and adept application of a variety of treatment technologies are imperative.

Cold work die steel Cr12Mo1V1 is often used in metal plastic forming processing such as spinning, stamping, quenching, and tempering. It has a high hardness but still contains a lot of unstable residual austenite, which is prone to phase change in the service process to cause stress concentration, seriously affecting the contact fatigue performance of components. This paper studied the effects of different heat treatment processes on microhardness, residual stress, residual austenite content, and contact fatigue properties of Cr12Mo1V1 steel members by combining the cryogenic process with low-temperature and high-temperature tempering. The results show that the residual austenite content of the components can be reduced from 21.3 to 2.6%, and the contact fatigue life of the components can be increased by 1.89 times compared with the low-temperature tempering method.

Degenerative diseases such as cancer usually involve more than one pathological process. Therefore, attempts to combat such diseases with monotherapeutic approaches may not always do so efficiently. For this reason, the use of combination therapy with modalities that target different disease pathways represents an alternative strategy. Photodynamic therapy (PDT) has already been established as an alternative therapy for the treatment of various types of malignant disorders, including oesophageal, lung and bladder cancer as well as other degenerative diseases. This technique involves the administration of a tumor localizing photosensitizer followed by its activation with light of a specific wavelength. In the presence of tissue oxygen, the photoactive sensitizer triggers a series of photochemical and photobiological processes that may lead to direct cancer cell damage, tumor microvascular occlusion and host immune response. Due to these multiple actions, PDT has increasingly gained recognition as a potential adjuvant for conventional cancer treatments. Several preclinical studies and some clinical trials suggest that the use of PDT in combination with established treatments or with newly-developed modalities may be of benefit as compared to the individual modalities. In this review, we briefly introduce the reader to the main photobiological aspects of PDT, and then discuss the use of PDT in combination with other pharmacological approaches for the treatment of cancer.

Insomnia is highly prevalent in clinical practice, occurring in up to 50% of primary care patients. Insomnia can present independently or alongside other medical conditions or mental health disorders and is a risk factor for the development and exacerbation of these other disorders if not treated. In 2016, the American College of Physicians recommended that insomnia be specifically targeted for treatment. The recommended first-line treatment for insomnia, whether the underlying cause has been identified or not, is cognitive behavioural therapy for insomnia (CBT-I). Currently, there is no global consensus regarding which pharmacological treatment has the best efficacy or risk-benefit ratio. Both CBT-I and pharmacological intervention are thought to have similar acute effects, but only CBT-I has shown durable long-term effects after treatment discontinuation. Administering a combined treatment of CBT-I and medication could decrease the latency to treatment response, but might diminish the durability of the positive treatment effects of CBT-I.

Combined checkpoint blockade (e.g., PD1/PD-L1) with traditional clinical therapies can be hampered by side effects and low tumour-therapeutic outcome, hindering broad clinical translation. Here we report a combined tumour-therapeutic modality based on integrating nanosonosensitizers-augmented noninvasive sonodynamic therapy (SDT) with checkpoint-blockade immunotherapy. All components of the nanosonosensitizers (HMME/R837@Lip) are clinically approved, wherein liposomes act as carriers to co-encapsulate sonosensitizers (hematoporphyrin monomethyl ether (HMME)) and immune adjuvant (imiquimod (R837)). Using multiple tumour models, we demonstrate that combining nanosonosensitizers-augmented SDT with anti-PD-L1 induces an anti-tumour response, which not only arrests primary tumour progression, but also prevents lung metastasis. Furthermore, the combined treatment strategy offers a long-term immunological memory function, which can protect against tumour rechallenge after elimination of the initial tumours. Therefore, this work represents a proof-of-concept combinatorial tumour therapeutics based on noninvasive tumours-therapeutic modality with immunotherapy. Immunotherapy for the treatment of cancer can be complicated by side effects and poor efficacy. Here, the authors use a nanoparticle-based approach in combination with a TLR7 agonist and sonodynamic therapy, and find that when used together with anti-PD-L1, tumour formation and metastases are impacted.

Ferroptosis, a form of regulated cell death that is induced by excessive lipid peroxidation, is a key tumour suppression mechanism 1 – 4 . Glutathione peroxidase 4 (GPX4) 5 , 6 and ferroptosis suppressor protein 1 (FSP1) 7 , 8 constitute two major ferroptosis defence systems. Here we show that treatment of cancer cells with GPX4 inhibitors results in acute depletion of N -carbamoyl- l -aspartate, a pyrimidine biosynthesis intermediate, with concomitant accumulation of uridine. Supplementation with dihydroorotate or orotate—the substrate and product of dihydroorotate dehydrogenase (DHODH)—attenuates or potentiates ferroptosis induced by inhibition of GPX4, respectively, and these effects are particularly pronounced in cancer cells with low expression of GPX4 (GPX4 low ). Inactivation of DHODH induces extensive mitochondrial lipid peroxidation and ferroptosis in GPX4 low cancer cells, and synergizes with ferroptosis inducers to induce these effects in GPX4 high cancer cells. Mechanistically, DHODH operates in parallel to mitochondrial GPX4 (but independently of cytosolic GPX4 or FSP1) to inhibit ferroptosis in the mitochondrial inner membrane by reducing ubiquinone to ubiquinol (a radical-trapping antioxidant with anti-ferroptosis activity). The DHODH inhibitor brequinar selectively suppresses GPX4 low tumour growth by inducing ferroptosis, whereas combined treatment with brequinar and sulfasalazine, an FDA-approved drug with ferroptosis-inducing activity, synergistically induces ferroptosis and suppresses GPX4 high tumour growth. Our results identify a DHODH-mediated ferroptosis defence mechanism in mitochondria and suggest a therapeutic strategy of targeting ferroptosis in cancer treatment. DHO dehydrogenase regulates ferroptosis by preventing mitochondrial lipid peroxidation and its inhibition suppresses growth in tumours with low levels of GPX4.

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2–20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1–69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7–13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05–0.87). A total of 56.2% (95% CI 41.1–70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406). A safety and efficacy trial of a single intratumoral dose of the oncolytic adenovirus DNX-2401 followed by intravenous anti-PD-1 pembrolizumab in patients with recurrent glioblastoma shows an encouraging clinical benefit rate and 12 months overall survival.

The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy). DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0–2 or return to baseline at 90 days, with a non-inferiority margin of –0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants. Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference –0·051, two-sided 95% CI –0·160 to 0·059; per-protocol risk difference –0·062, two-sided 95% CI –0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22–13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46–1·84). We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment. Australian National Health and Medical Research Council and Stryker USA.