PD-1/PD-L1 signaling is a key factor of local immunosuppression in the tumor microenvironment. Immune checkpoint inhibitors targeting PD-1/PD-L1 signaling have achieved tremendous success in clinic. ...However, several types of cancer are particularly refractory to the anti-PD-1/PD-L1 treatment. Recently, a series of studies reported that IFN-γ can stimulate cancer cells to release exosomal PD-L1 (exoPD-L1), which possesses the ability to suppress anticancer immune responses and is associated with anti-PD-1 response. In this review, we introduce the PD-1/PD-L1 signaling, including the so-called 'reverse signaling'. Furthermore, we summarize the immune treatments of cancers and pay more attention to immune checkpoint inhibitors targeting PD-1/PD-L1 signaling. Additionally, we review the action mechanisms and regulation of exoPD-L1. We also introduce the function of exoPD-L1 as biomarkers. Finally, we review the methods for analyzing and quantifying exoPD-L1, the therapeutic strategies targeting exoPD-L1 to enhance immunotherapy and the roles of exoPD-L1 beyond cancer. This comprehensive review delves into recent advances of exoPD-L1 and all these findings suggest that exoPD-L1 plays an important role in both cancer and other fields.
The sludge in situ reduction process by inserting an anaerobic side-stream reactor (ASSR) in a sludge return line provides a cost-effective approach to reduce sludge production in activated sludge ...systems. In this study, four pilot-scale membrane bioreactors (MBRs), including an AO-MBR for control, ASSR coupled MBR (ASSR-MBR), a MBR with ASSR packed with carriers (AP-MBR) and an AP-MBR with part of sludge ultrasonicated before fed into ASSR (AUP-MBR) were operated in parallel to investigate enhancing effects of ultrasonication and packing carriers on sludge reduction and pollutants removal performance under both normal and low temperature. Low temperature showed negligible impact on COD removal, deteriorated NH4+N and TN removal from 98.3% to 69.7% at 21.6 °C to 92.5% and 48.8% at 2.6 °C, and decreased sludge reduction efficiency (SRE) in ASSR-MBR. Packing carriers and ultrasonication both enhanced sludge reduction, especially under low temperature with SRE values increased from 8.2% of ASSR-MBR to 17.1% of AP-MBR and 32.6% of AUP-MBR at 4.5 ± 2.5 °C. Packing carriers and ultrasonication increased cell rupture by 11.1% and 14.5% in aerobic MBR, enhanced protease activity in ASSR by 60.0% and 116.3%, and reduced ATP content for heterotrophic metabolism by 31.4% and 7.3%, respectively. MiSeq sequencing results showed that packing carriers enriched hydrolytic bacteria (Terrimonas, Dechloromonas and Woodsholea), slow growers (Sulfuritalea, Thauera and Azospira) and predatory bacteria (Bdellovibrio and norank_Saprospiraceae), while ultrasonication further enriched hydrolytic bacteria (norank_Saccharibacteria and Ferruginibacter). Packing carriers is more cost-effective than ultrasonication to enhance sludge reduction by partial damage to bacterial cells and promoting better interaction between bacteria, enzymes and substrates to favor particles hydrolysis.
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•Enhancement of sludge reduction in anaerobic side-stream reactor (ASSR) was studied.•Packing carriers enhanced sludge reduction from 8.2% to 17.1% at 1.0–9.0 °C.•Combining ultrasonication and packing carriers enhanced sludge reduction by 297%.•Combination enhanced cell rupture and protease activity, and reduced ATP content.
A sludge process reduction activated sludge (SPRAS), with a sludge process reduction module composed of a micro-aerobic tank and a settler positioned before conventional activated sludge process, ...showed good performance of pollutant removal and sludge reduction. Two SPRAS systems were operated to investigate effects of micro-aeration on sludge reduction performance and microbial community structure. When dissolved oxygen (DO) concentration in the micro-aerobic tank decreased from 2.5 (SPH) to 0.5 (SPL) mg/L, the sludge reduction efficiency increased from 42.9% to 68.3%. Compared to SPH, activated sludge in SPL showed higher contents of extracellular polymeric substances and dissolved organic matter. Destabilization of floc structure in the settler, and cell lysis in the sludge process reduction module were two major reasons for sludge reduction. Illumina-MiSeq sequencing showed that microbial diversity decreased under high DO concentration. Proteobacteria, Bacteroidetes and Chloroflexi were the most abundant phyla in the SPRAS. Specific comparisons down to the class and genus level showed that fermentative, predatory and slow-growing bacteria in SPL community were more abundant than in SPH. The results revealed that micro-aeration in the SPRAS improved hydrolysis efficiency and enriched fermentative and predatory bacteria responsible for sludge reduction.
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•Effects of micro-aeration on sludge reduction and microbial community were studied.•The micro-aerobic sludge reduction process, SPRAS, reduces observed yield by 68.3%.•Flocs disintegration and cell lysis were two major mechanisms for sludge reduction.•Illumina-MiSeq sequencing showed increasing microbial diversity with micro-aeration.•Micro-aeration in SPRAS enriched fermentative, predatory and slow-growing bacteria.
Adoptive cell therapy using T cell receptor-engineered T cells (TCR-T) is a promising approach for cancer therapy with an expectation of no significant side effects. In the human body, mature T cells ...are armed with an incredible diversity of T cell receptors (TCRs) that theoretically react to the variety of random mutations generated by tumor cells. The outcomes, however, of current clinical trials using TCR-T cell therapies are not very successful especially involving solid tumors. The therapy still faces numerous challenges in the efficient screening of tumor-specific antigens and their cognate TCRs. In this review, we first introduce TCR structure-based antigen recognition and signaling, then describe recent advances in neoantigens and their specific TCR screening technologies, and finally summarize ongoing clinical trials of TCR-T therapies against neoantigens. More importantly, we also present the current challenges of TCR-T cell-based immunotherapies, e.g., the safety of viral vectors, the mismatch of T cell receptor, the impediment of suppressive tumor microenvironment. Finally, we highlight new insights and directions for personalized TCR-T therapy.
Since the coronavirus disease 2019 (COVID-19) epidemic, insomnia has become one of the longer COVID-19 symptoms. This study aimed to investigate insomnia among COVID-19 survivors and explore the ...occurrence and influencing factors of insomnia. A cross-sectional study was performed from December 2022 to February 2023 through an online questionnaire star survey with 8 questions. The insomnia severity index scale (ISI) was used to assess the severity of insomnia. Univariate analysis was used to analyze the factors related to COVID-19 infection. A total of 564 participants (183 males and 381 females) were surveyed in the present study. The prevalence of insomnia was 63.12%. Among these insomnia patients, there were 202 (35.82%) with sub-threshold symptoms, 116 (20.57%) with moderate symptoms, and 38 (6.74%) with severe symptoms. Univariate analysis indicated that there were statistically significant differences in the prevalence of insomnia among COVID-19 survivors of different ages, occupations, and educational levels (P < .05). Of the 356 insomnia patients, 185 (51.97%) did not take any measures against insomnia, while those who took drugs only, physical exercise only, drugs and physical exercise, and other measures were 90 (25.28%), 42 (11.80%), 17 (4.78%), and 22 (6.18%), respectively. Additionally, of the 107 insomnia patients with drug therapy, 17 (15.89%) took estazolam, 16 (14.95%) took alprazolam, 39 (36.45%) took zopiclone, and 35 (32.71%) took other drugs to improve insomnia symptoms. The prevalence of insomnia symptoms remains high among COVID-19 survivors in China. Education level and occupation may be the influencing factors. Unfortunately, most patients with insomnia do not take corresponding treatment measures.
•Inhibitory effect of humic substances on struvite precipitation was studied.•Humic substances inhibited struvite precipitation at pH 8.0–9.0 and lowMg/P ratio.•Humic substances changed structure and ...morphology of precipitated struvite crystals.•Coprecipitation of humic substances compromised precipitated struvite purity.
Humic substances (HS) are a major fraction of dissolved organic matters in wastewater. The effect of HS on phosphorus removal by struvite precipitation was investigated using synthetic wastewater under different initial pH values, Mg/P molar ratios and HS concentrations. The composition, morphology and thermal properties of harvested precipitates were analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM) and thermo-gravimetric analysis (TGA), respectively. It showed that inhibition effect of HS reached its maximum value of 48.9% at pH 8.0, and decreased to below 10% at pH>9.0. The increase of Mg/P ratio enhanced phosphorus removal efficiency, and thus reduced the influence of HS on struvite precipitation. At pH 9.0, the inhibitory effect of initial HS concentration matched the modified Monod model with half maximum inhibition concentration of 356mgL−1, and 29% HS was removed in conjunction with struvite crystallisation. XRD analysis revealed that the crystal form of struvite precipitates was changed in the presence of HS. The morphology of harvested struvite was transformed from prismatic to pyramid owing to the coprecipitation of HS on crystal surface. TGA results revealed that the presence of HS could compromise struvite purity.
The process performance of a full-scale sludge process reduction activated sludge (SPRAS) system in long-term operation were investigated by inserting a micro-aerobic tank and a clarifier before ...conventional activated sludge process. The full-scale SPRAS for industrial park wastewater treatment achieved efficient pollutants removal and a low observed sludge yield of 0.074 g SS/g COD. Batch tests showed that influent feeding into the micro-aerobic tank favored sludge reduction, and obtained a sludge decay constant of 0.168 d−1. The SPRAS enriched slow growers and hydrolytic bacteria for sludge reduction, showed high simultaneous nitrification and denitrification efficiency in the micro-aerobic tank with abundant denitrifying bacteria, and improved sludge settleability by enriching floc-forming bacteria. Process configuration of the SPRAS was beneficial to enhance maintenance metabolism, cyclic micro-aerobic and anaerobic uncoupling, and lysis-cryptic growth for sludge reduction. Techno-economic analysis showed that the SPRAS greatly reduced sludge production with small footprint and low cost.
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•An Al recovery process was developed for sulfate removal by ettringite precipitation.•Al recovery above 98.4% was obtained at pH 3.0, suspended solid of 9.8 g/L and 303 K.•Ettringite ...(Ett) dissolution was divided into two stages with gypsum precipitation.•Pilot-scale test showed 66.0% sludge reduction and 35.1% cost saving by Al recovery.•Ett precipitation with Al recovery is cost-effective for industrial application.
A novel sulfate removal process via ettringite precipitation was developed by dissolving ettringite and recycling Al3+ under low pH condition. Effects of solid to liquid ratios, pH and temperature on ettringite dissolution, Al recovery and transformation of precipitates were investigated by batch experiments. The optimum condition for Al recovery is pH =3.0, suspended solid of 9.8 g/L and temperature below 303 K. Ettringite dissolution consists of two stages, (i) rapid but inconsistent dissolution with the fastest release of sulfate, followed by calcium, and then Al(OH)63−; (ii) slow dissolution of Al(OH)63- core and gypsum precipitation. Dissolution of Al(OH)63- core follows the first-order kinetics with activation energy of 41.18 kJ/mol, while gypsum re-precipitation follows the second-order kinetics with activation energy of 26.36 kJ/mol. Long-term results of pilot-scale systems for treatment of real flue gas desulfurization wastewater showed that the process achieved sulfate removal of 98.3%–99.5% and Al recovery above 98.4%, and converted 98.8% sulfate in ettringite to CaSO4, which resulted in 66.0% of sludge reduction and improved sludge dewaterability. Economic evaluation shows that the process with Al recovery reduces cost of ettringite precipitation by 35.1%, and is highly feasible and cost-effective for industrial application of high-sulfate content wastewater treatment.
The aim of this study was to investigate membrane fouling performance of anaerobic side-stream reactor (ASSR) coupled membrane reactors (MBR), and effects of representative enhancement strategy, ...namely packing carriers and low-strength ultrasonication, on sludge properties and membrane fouling by four pilot-scale MBRs. Compared to anoxic/oxic MBR (AO-MBR) for control, ASSR coupled AO-MBR (ASSR-MBR), ASSR-MBR with ASSR packed with carriers (AP-MBR) and AP-MBR with part of sludge ultrasonicated before fed into ASSR (AUP-MBR) reduced sludge production by 8.4%, 17.5% and 32.9% with efficient pollutants removal. ASSR-MBR showed more severe membrane fouling because inserting ASSR disintegrated sludge floc structure, increased the secretion of extracellular polymeric substances (EPS) and deteriorated viscoelastic property of sludge. Packing carriers in ASSR alleviated membrane fouling of ASSR-MBR by inhibiting EPS-secreting bacteria (Flavobacteriia, γ-Proteobacteria, δ-Proteobacteria and norank_Saccharibacteria), enlarging particle size and improving dewaterability. AUP-MBR showed the most severe membrane fouling and obvious cake layer fouling because ultrasonication disintegrated sludge to small particles, increased adherence property of EPS, and deteriorated dewaterability and viscoelastic property of sludge. MiSeq sequencing revealed Proteobacteria and Bacteroidetes were responsible for membrane fouling at the phylum level, and norank_Neisseriaceae, Arcobacter, norank_Parcubacteria and Mycobacterium were dominant genera easily attached on membrane surface.
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•Membrane fouling (MF) of anaerobic side-stream reactor (ASSR) - MBR was studied.•ASSR-MBR deteriorated MF, dewaterability and flowability due to sludge reduction.•Carriers in ASSR alleviated MF by inhibiting EPS secretion and enlarging particles.•Ultrasonication caused severe MF due to flocs disintegration and high EPS adhesivity.•MiSeq sequencing revealed dominant bacteria easily attached on membrane surface.
One of the main challenges in industrial wastewater treatment and recovery is the removal of sulfate, which usually coexists with Ca2+ and Mg2+. The effect of Mg2+ on sulfate removal by ettringite ...precipitation was investigated, and the process was optimized in the absence and presence of Mg2+. In the absence of Mg2+, the optimum conditions with sulfate removal of 99.7% were obtained at calcium-to-sulfate ratio of 3.20, aluminum-to-sulfate ratio of 1.25 and pH of 11.3 using response surface methodology. In the presence of Mg2+, sulfate removal efficiency decreased with increasing Mg2+ concentration, and the inhibitory effect of Mg2+ matched the competitive inhibition Monod model with half maximum inhibition concentration of 57.4 mmol/L. X-ray diffraction and Fourier transform infrared spectroscopy analyses of precipitates revealed that ettringite was converted to hydrotalcite-type (HT) compound in the presence of Mg2+. The morphology of precipitates was transformed from prismatic crystals to stacked layered crystals, which confirmed that Mg2+ competes with Ca2+ for Al3+ to form HT compound. A two-stage process was designed with Mg2+ removal before ettringite precipitation to eliminate the inhibitory effect, and is potential to realize sludge recovery at the same time of effective removal of sulfate and hardness.
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•Sulfate removal by ettringite precipitation was optimized in the absence of Mg2+.•Mg2+ competes with Ca2+ for Al3+ and inhibits sulfate removal as ettringite.•Ettringite was converted to hydrotalcite-type compound in the presence of Mg2+.•A two-stage process was designed to eliminate Mg2+ inhibition and recover sludge.
