Short Retention Research Articles

Comparative evaluation of different substrates compiled in column‐type vertical‐flow constructed wetlands to remove heavy metals

AbstractHeavy metals (HMs), like chromium (Cr), manganese (Mn), and nickel (Ni), are toxic pollutants frequently detected in industrial wastewater. In this study, column‐type vertical‐flow constructed wetlands (CWs) filled with different substrates were examined for their ability to remove Cr, Mn, and Ni, focusing on their applicability to high HM concentrations (tens of mg/L) and short hydraulic retention times (2 days). Five candidate substrates—gravel, limestone, reddish soil, wood pellets, and activated carbon—were screened for their ability to remove 6 mg/L of the three HMs, revealing that reddish soil and activated carbon removed all three HMs efficiently. Further experiments to remove 60 mg/L of HMs were conducted using CWs filled with reddish soil or activated carbon with or without planting Phragmites australis. The results indicated that (1) substrate adsorption contributed exclusively to HM removal and the effects of planting may be negligible, and (2) activated carbon (removal efficiency of 74–99%, 98–99%, and 99% for Cr, Mn, and Ni, respectively) is likely a more promising substrate than reddish soil (removal efficiency of 90–99%, 48–99%, and 61–99% for Cr, Mn, and Ni, respectively) in light of its ability to achieve efficient HM removal under high loading conditions.

Prolonging Treatment Window of Photodynamic Therapy with Self-Amplified H2 O2 -Activated Photodynamic/Chemo Combination Therapeutic Nanomedicines.

Photodynamic therapy (PDT) is a promising approach to cancer therapy. However, the relatively short tumor retention time of photosensitizers (PSs) makes it difficult to catch the optimal treatment time and restricts multiple PDT within a single injection. In this study, a tumor-specific phototheranostic nanomedicine (DPPa NP) is developed for photodynamic/chemo combination therapy with a prolonged PDT treatment window. DPPa NP is prepared via encapsulating a hydrophobic oxidized bovine serum albumin (BSA-SOH)-conjugatable PS DPPa with amphiphilic H2 O2 -activatable chlorambucil (CL) prodrug mPEG-TK-CL. The released CL under H2 O2 treatment can not only kill tumor cells but also upregulate reactive oxygen species levels within tumor cells, leading to the almost full release of cargoes. The released DPPa may conjugate with overexpressed BSA-SOH, which results in the recovery of the fluorescence signal and photodynamic effect. More importantly, such conjugation transfers DPPa from a small molecule PS into a macromolecular PS with a long tumor retention time and treatment window of PDT, which enables multiple PDT. This study thus provides an effective strategy to prolong the treatment window of PDT and enables tumor-specific fluorescence imaging-guided combination therapy.

Metagenomics insights into high-rate nitrogen removal from municipal wastewater by integrated nitrification, partial denitrification and Anammox at an extremely short hydraulic retention time

To achieve high-rate nitrogen removal in municipal wastewater treatment through anaerobic ammonia oxidation (Anammox), the nitrification, partial denitrification, and Anammox processes were integrated by a step-feed strategy. An exceptional nitrogen removal load of 0.224 kg N/(m3·d) was achieved by gradient-reducing the hydraulic retention time (HRT) to 5 h. Metagenomic analysis demonstrated that Nitrosospira could express all genes encoding ammonia oxidation under low nitrogen and dissolved oxygen conditions (less than 0.5 mg/L), enabling complete nitrification. With the short of HRT, the relative abundance of Thauera increased from 2.8 % to 6.4 %. Frequent substrate exchanges at such extremely short HRT facilitated enhanced synergistic interactions among Nitrosospira, Thauera, and Candidatus Brocadia. These findings provide a comprehensive understanding of the utilization of Anammox combined processes for high-speed nitrogen removal in municipal wastewater treatment and the microbial interactions involved.

A new sulfur bioconversion process development for energy- and space-efficient secondary wastewater treatment

Harvesting organic matter from wastewater, chemical enhanced primary treatment for instance, is widely applied to maximize energy recovery; however, it limits the applicability of secondary treatment for acceptable effluent discharge into surface water bodies. To turn this bottleneck issue into an opportunity, this study developed oxygen-induced thiosulfatE production duRing sulfATe reduction (ERATO) to provide efficient electron donor for denitrification or partial denitrification anammox in wastewater treatment. Typical pretreated wastewater was synthesized with chemical oxygen demand of 110 mg/L, sulfate of 50 mg S/L, ammonium of 30 mgN/L, and varying dissolved oxygen (DO) and was fed into a moving-bed biofilm reactor (MBBR) with a short hydraulic retention time of 40 min. The ORP maintained at − 311 mV in the bioreactor, indicating that the influent DO was vanished immediately when it enters the bioreactor. In 349 days’ continuous operation, the surface-specific sulfate reduction rate reached 0.42 g S/(m2·d). Notably, the formation rate of thiosulfate reached 0.12–0.18 g S/(m2·d) with a high thiosulfate-Sproduced/sulfide-Sproduced ratio of 38–73% when influent DO was 2.7–3.6 mg/L, much higher than 0–17% obtained in previously reported sulfate-reducing process. Then, batch tests and metabolism analysis were conducted to confirm the oxygen effect on thiosulfate formation, and to explore the mechanism of oxygen-induced thiosulfate formation in ERATO. Results examined that oxygen supply promoted the thiosulfate-Sproduced/sulfide-Sproduced ratio from 4% to 24–26%, demonstrated that S0 and sulfate were critical for thiosulfate production, and indicated that oxygen induces thiosulfate formation mainly through: sulfide first oxidized to S0 which then reacts with sulfite derived from oxygen-regulated biological sulfate reduction (S0 + SO32−→S2O32−). The proposed compact ERATO process with high thiosulfate production, supporting space- and energy-efficient secondary wastewater treatment.

Valorization of potato starch wastewater using anaerobic acidification coupled with Chlorella sorokiniana cultivation

Wastewater from the potato processing industry called protamylasse is rich in proteins and carbohydrates that potentially can be valorized through cultivation of microalgae by mixotrophic metabolism. However, the complex organic compounds are a challenge, as algae grow best on simple compounds such as volatile fatty acids (VFA). This study demonstrates a new two-stage system. First, VFA production was achieved by testing mesophilic and thermophilic anaerobic acidification (AA) at a short hydraulic retention time (HRT; 3.3 and 5 days) resulting in the release of ammonium and phosphate. HRT of 5 days and thermophilic conditions was optimal considering the high acetate yield of 0.23 g and 22 ml CH4 per g volatile solids (VS). Then, Chlorella sorokiniana was chosen based on the obtained growth rate, and better adaption in ammonium-rich AA effluent after screening several tested microalgae (Chlorella sorokiniana, Chlorella vulgaris, Scenedesmus obliquus, and Haematococcus pluvialis). It was cultivated for valorization of nutrients and organics and successfully upscaled to 25 L photobioreactor (PBR) scale under both batch and continuous operation with high dosage of 25% (8.2 g L−1 of VS) of AA effluent at an HRT of 5 days in the PBR. Chlorella sorokiniana removed more than 99% of the chemical oxygen demand (COD) and the VFA during continuous flow PBR operation. This approach contributed to the final removal efficiency of 71%, 91%, and 78% for phosphorus, nitrate, and ammonia, respectively, and production of microalgae biomass with more than 73% protein. Thus, a promising process for simultaneous treatment of high strength wastewater for microalgal protein production.

Dual-targeting lanthanide-ICG-MOF nanoplatform for cancer Theranostics: NIR II luminescence imaging guided sentinel lymph nodes surgical navigation.

Sentinel lymph node imaging is important for breast tumor staging and prediction of postoperative metastasis. However, clinical sentinel lymph node imaging has limitations such as low specificity, low contrast, and short retention time. The combination of bio-conjugates chemistry and luminescence technology may achieve the specific targeting effect. In this research, we designed a dual-targeting composite nanoprobe (∼50nm) using a metal-organic framework (MOF) as carrier, loaded with lanthanide and ICG, and combined with hyaluronic acid and folic acid to detect metastatic lymph nodes. The coupled hyaluronic acid and folic acid can target to the tumor cells and dentritic cells with a dual-targeting effect. The FA-HA/ZIF-8@ICG nanoprobes can accumulate rapidly in sentinel lymph node with a stronger luminescence intensity (1.6 times) than that of normal popliteal lymph nodes in vivo, thus distinguish metastatic sentinel lymph node from normal effectively. Furthermore, due to the MOF carrier, the integrated lanthanide and near-infrared dye by transferring the absorbed excitation energy from ICG to Nd3+ can enhance the signal-to-background ratio of NIR II imaging and have long retention time in vivo imaging. Finally, the FA-HA/ICG@Ln@ZIF-8 nanoplatform increased the penetration depth and contrast of imaging, prolonged the retention time, and achieved the sentinel lymph nodes surgical resection. This study has important implications for lymph node imaging and surgical navigation.

Metabolic Functional Profiles of Microbial Communities in Methane Production Systems Treating Winery Wastewater

This study investigated the impact of process configuration and conditions on microbial communities and metabolic pathways in the anaerobic digestion of winery effluents. Four system configurations were analyzed for taxonomic and functional profiles using 16S rRNA gene sequencing and Tax4Fun2. Sporolactobacillus, Prevotella, and Acetobacter dominated (> 70%) in the acidogenic reactor with 5277 conserved functions across configurations. In the methanogenic reactor, methane production relied on Methanosaeta in the single-stage configuration (13%) and five archaea genera in the two-stage configuration (18%). Thermophilic conditions favored syntrophic acetate oxidation and hydrogenotrophic methanogenesis by Methanothermobacter (65%), significantly changing due to temperature. The two-stage configuration exhibited 3.0 times higher functional redundancy than the single-stage configuration. Mesophilic conditions displayed 2.5 times greater functional redundancy than thermophilic conditions. High organic loading rate and short hydraulic retention time reduced functional redundancy by 1.5 times. Assessing microbial functionality beyond their composition is crucial to understand stability and performance of anaerobic digestion systems.

Oxygen limitation in aerobic polyhydroxyalkanoates production from sewage sludge anaerobic fermentation liquids under low and medium organic loading rate

The present study describes the microbial production of polyhydroxyalkanoates (PHA) from thermally pre-treated sewage sludge at pilot scale level, investigating for the first time the effect of the organic loading rate (OLR) under oxygen limitation on biomass storage properties and kinetics. Polymer characteristics have been also evaluated. The selection/enrichment of PHA-storing biomass was successfully achieved in a Sequencing Batch Reactor (SBR) under short hydraulic retention time (HRT; 2 days). Low OLR (2.05 g COD/L d) was ideal for the selection of an efficient PHA-producing consortium cultivated under limited oxygen availability. In the fed-batch accumulation conducted under high DO regime, such biomass was characterized by 51% of PHA content on cell dry weight, with a related storage yield (YP/Sbatch) of 0.61 CODPHA/CODS. On the contrary, medium OLR (4.56 g COD/L d) was not technically feasible to sustain the required consortium's selection under low DO regime. The PHA produced by biomass cultivated under low DO regime was characterized higher thermal stability and crystalline domain compared to PHA traditionally produced under high DO regime. The mass balance assessment highlighted a global yield of 51 g PHA/kg VS (volatile solids of thickened sludge), which was 9% lower than yield obtained under high DO regime, in the face of a realistic reduction of the energy cost of the process.

Molecular Tailoring to Achieve Long‐Term Plasticity in Organic Synaptic Transistors for Neuromorphic Computing

Organic synaptic transistors (OSTs) using intrinsic polymer semiconductors are demonstrated to be suitable for neuromorphic bioelectronics. However, diketopyrrolopyrrole (DPP)‐based copolymers are not applicable to neuromorphic computing systems because the DPP polymer film has demonstrated only short‐term plasticity with short retention (<50 ms) in synaptic devices because of their intrinsic difficulty of electrochemical doping. To expand their applications toward neuromorphic computing that requires long‐term plasticity, artificial synapses with extended retention time should be developed. Herein, molecular tailoring approach to extend the retention time in the ion‐gel‐gated OSTs that use DPP is suggested. The molecular structure is controlled by changing alkyl spacer lengths of side chains. As a result, the doping process is more favorable in DPP with long alkyl spacer, which is confirmed by high doping concentration and slow dedoping rate. Therefore, dedoping of ions is more suppressed in DPP with long alkyl side chain that exhibits extended retention time (≈800 s) of the OSTs. These optimized DPP‐based OSTs obtain high pattern recognition accuracy of ≈96.0% in simulations of an artificial neural network. Molecular tailoring strategies provide a guideline to overcome the intrinsic problem of short synaptic retention time of the OSTs for use in neuromorphic computing.

Pilot-scale study on the performance of high-rate DAF based on removal of organic precursors and formation characteristics of disinfection by-products

In recent years, there has been an increased focus on the design and development of dissolved air flotation (DAF) with a high surface loading rate (SLR), but little research has been conducted using advanced natural organic matter characterization techniques. This research thus investigates the performance of pilot-scale DAF (10–30 m h–1) and compares them with those for a full-scale coagulation–flocculation–sedimentation (CFS) system based on the reduction of organic precursors, different molecular weight (MW) fractions characterized by liquid chromatography with organic carbon detection, and disinfection by-products. The removal of dissolved organic carbon (DOC) decreased with increasing SLR, ranging from 29 % to 38 %. This may be because of the short flocculation retention time for high SLR. Thus, achieving a similar removal of DOC by high SLR required higher coagulant doses. Furthermore, the organic precursors were measured lower in the high-rate DAF effluent than the CFS, maybe because of the high coagulation pH of the CFS effluent (7.5–8). Similarly, the concentration of different MW fractions, especially biopolymers and building blocks, was lower in the high-rate DAF effluent than in the CFS. The removal of biopolymers was 74.64 % and 87.20 % for the CFS and high-rate DAF, respectively. Likewise, 2.78 % and 27.09 % for the CFS and high-rate DAF, respectively, for building blocks. The normalized trihalomethanes/DOC and chloralhydrate/DOC were higher for the CFS than the high-rate DAF. Coagulation chemistry (pH, coagulant doses, and retention time) strongly influences the DAF and CFS unit performance and should not be neglected.

Acclimatizing waste activated sludge in a thermophilic anaerobic fixed-bed biofilm reactor to maximize biogas production for food waste treatment at high organic loading rates

Thermophilic anaerobic digestion (TAD) provides a promising solution for sustainable high-strength waste treatment due to its enhanced methane-rich biogas recovery. However, high organic loading rates (OLR) exceeding 3.0 kgCOD/m3/day and short hydraulic retention times (HRT) below 10 days pose challenges in waste-to-energy conversion during TAD, stemming from volatile fatty acids (VFAs) accumulation and methanogenesis failure. In this study, we implemented a stepwise strategy for acclimatizing waste activated sludge (WAS) in a thermophilic anaerobic fixed-bed biofilm reactor (TA-FBBR) to optimize methanogen populations, thereby enhancing waste-to-energy efficiencies under elevated OLRs in food waste treatment. Results showed that following stepwise acclimatization, the TA-FBBR achieved stable methane production of approximately 5.8 L/L-reactor/day at an ultrahigh OLR of ∼20 kgCOD/m3/day and ∼15 kgVS/m3/day at 6-day HRT in food waste treatment. The average methane yield reached 0.45 m3/kgCODremoval, attaining the theoretical production in TAD. Moreover, VFA concentrations were stabilized below 1000 mg/L at the ultrahigh OLR under 6-day HRT, while maintaining an acetate/propionate ratio of > 1.8 and a VFA/TAK ratio of < 0.3 serving as effective indicators of system stability and methane yield potential. The microbial community analysis revealed that the WAS acclimatization strategy fostered the microbial diversity and abundance of Methanothermobacter and Methanosarcina. Methanosarcina in the biofilm were observed to be twice as abundant as Methanothermobacter, indicating a potential preference for biofilm existence among methanogens. The findings demonstrated an effective strategy, specifically the stepwise acclimatization of WAS in a thermophilic fixed-bed biofilm reactor, to enhance the food waste treatment performance at high OLRs, contributing valuable mechanistic and technical insights for future sustainable high-strength waste management.

Resilience, depression and their effect on nurse retention: a survey in rural Indonesia.

Health professionals' maldistribution and retention in underserved areas are global problems. Burnout drives health professionals to leave rural areas. Chronic burnout is linked to depression, and nurses have a higher risk for depression than the general population. Studies suggest that increasing resilience may reduce depression. However, little is known about the effect of resilience on nurses' depression and their rural retention. This study aims to understand the impact of resilience and depression on nurses' retention in rural areas. An online cross-sectional survey on registered nurses was conducted in July - August 2021 in a rural province in Indonesia. The survey measured the nurses' resilience, depression level, and work duration. A total of 1050 participants joined the study. The results suggest that resilience in nurses is negatively correlated to depression and retention. The mildly depressed group had the shortest retention. There was no difference in the work duration, depression, and resilience scores between the underserved and non-underserved regencies in the province. Although not all our hypotheses are supported, some interesting results were obtained. In a previous study, the more senior the doctor, the higher the resilience; in this nurse analysis, the opposite was true - senior nurses were the least resilient. As found in other studies, resilience is negatively correlated to depression. So, resilience training may still benefit the depressed group. Improvement of health professionals' rural retention requires approaches tailored to each profession. Resilience training may be beneficial to retain nurses through mild depression treatment.

Mesenchymal stromal cell–derived magnetic nanovesicles for enhanced skin retention and hair follicle growth

Background aimsExtracellular vesicles and exosome-mimetic nanovesicles (NVs) derived from mesenchymal stromal cells (MSCs) have emerged as promising to promote hair growth. However, short local skin retention after subcutaneous administration hinders their clinical applications. MethodsIn this study, we prepared magnetic nanovesicles (MNVs) from iron oxide nanoparticle–incorporated MSCs. MNVs contained more therapeutic growth factors than NVs derived from naive MSCs, and their localization and internalization were manipulated by external magnetic field. ResultsFollowing the subcutaneous injection of MNVs into a mouse model of depilation-induced hair regeneration, the magnetic attraction increased their skin retention. Then, the cellular proliferation and β-catenin signaling in hair follicles (HF) were markedly enhanced by MNV injection and magnetic field application. Furthermore, an acceleration of HF growth was revealed by histological analysis. ConclusionsThe proposed strategy can enhance the therapeutic potential of MSC-derived NVs for hair regeneration and other dermatological diseases.

High drug loading hydrophobic cross-linked dextran microspheres as novel drug delivery systems for the treatment of osteoarthritis

Drug delivery via intra-articular (IA) injection has proved to be effective in osteoarthritis (OA) therapy, limited by the drug efficiency and short retention time of the drug delivery systems (DDSs). Herein, a series of modified cross-linked dextran (Sephadex, S0) was fabricated by respectively grafting with linear alkyl chains, branched alkyl chains or aromatic chain, and acted as DDSs after ibuprofen (Ibu) loading for OA therapy. This DDSs expressed sustained drug release, excellent anti-inflammatory and chondroprotective effects both in IL-1β induced chondrocytes and OA joints. Specifically, the introduction of a longer hydrophobic chain, particularly an aromatic chain, distinctly improved the hydrophobicity of S0, increased Ibu loading efficiency, and further led to significantly improving OA therapeutic effects. Therefore, hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.

Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells.

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity invivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

Application of Hydrogen-Based Denitrification: Simultaneous Removal of Nitrate and Reactive Black 5 Dye from Textile Wastewater Containing Organic Matter

In this study, a hydrogen-based denitrification (HD) reactor was used to investigate the simultaneous treatment of nitrogen and decolorization in textile wastewater contaminated with organic matter. The reactor operated in two phases: without and with organic matter. Despite the short hydraulic retention time, the HD system successfully removed all pollutants, including nitrate, nitrite, reactive black-5 dye and chemical oxygen demand. The unhindered treatment efficiency for nitrogen and decolorization in the presence of organic pollutants was observed. With the addition of organic matter, the nitrogen removal efficiency increased slightly from 85% to 90–100%, and the decolorization rate doubled from 25% to 50–60%. Organic matter played a crucial role in stimulating heterotrophic bacteria during biological denitrification and acted as a carbon source facilitating biological denitrification and azo bond cleavage during dye degradation. Despite the generation of toxic byproducts and changes in the dominant microbial community, the treatment efficiency remained stable and improved. This approach offers a promising solution for enhancing treatment efficiency in textile wastewater, providing a cost-effective and environmentally friendly option for developing countries to treat wastewater before discharge.

An Evaluation of Nurse Anesthetists’ Acquisition and Retention of Knowledge and Skill Performance for Brief Basic Life Support and Advanced Cardiac Life Support Training

OBJECTIVE The purpose of this study was to evaluate the acquisition and retention of knowledge and skills of basic (BLS) and advanced cardiac life support (ACLS) for nurse anesthetists at Maharaj Nakorn Chiang Mai Hospital. METHODS The one-group pretest-posttest design study was used. BLS and ACLS training comprised a brief BLS and ACLS review and practice. Knowledge was assessed by multiple-choice questions. The BLS skills were assessed by observing CPR performance on a Resusci- Anne-skill meter manikin and ACLS skills were evaluated using ACLS scenarios. The knowledge and skills were assessed before and after the training weekly for four weeks, and then at three months after the training ended. RESULTS A total of 38 nurse anesthetists participated in the study. There were significant increases in BLS and ACLS knowledge and skills after the training. However, there was short retention of BLS and ACLS knowledge and skills at three months after the training. Foreign body airway obstruction and assessing unresponsiveness were the two most common of BLS skills degradation. While the primary and secondary assessment, assessing ACLS algorithms, electrocardiogram recognition and electrical therapy were the common skills performance of ACLS skills degradation. CONCLUSIONS After the BLS and ACLS training, the knowledge and skills were significantly improved but there was short retention of knowledge and skills at three months after the training. Regular refreshment of CPR education is recommended to enhance the retention of knowledge and practice of nurse anesthetists KEYWORDS knowledge and skills retention, nurse anesthetists, acquisition, basic life support, advanced cardiac life support

Green algae outcompete cyanobacteria in a shallow lake, Longhu Lake

Abstract Green algae are natural competitors of cyanobacteria, but we still do not know why green algae have a competitive advantage in shallow lakes. In this study, we used qPCR to quantify and monitor green algae and cyanobacteria in Longhu Lake. Our results showed that green algae were dominant in Longhu Lake, accounting for 71.80–80.31%. The temporal and spatial dynamics of green algal blooms were consistent with that of total organic nitrogen (TON), indicating that organic nitrogen may be the key trigger of green algal blooms. Nitrogen and phosphorus were excessive, and the peak of ammonia nitrogen occurred during the blooms, implying that ammonia nitrogen may be one of the important factors stimulating green algal blooms. Spearman correlation analysis and RDA analysis showed that green algae and cyanobacteria were positively correlated with water temperature, TON, and ammonia nitrogen, indicating that they have similar favorable growth conditions in Longhu Lake. Our results indicated that the combined effects of elevated water temperature, excessive nitrogen and phosphorus, non-stratification, and short water retention time could favor the competitive dominance of green algae in Longhu Lake. The findings here improve our understanding of the competition between green algae and cyanobacteria in shallow lakes.

Polarized Tunneling Transistor for Ultrafast Memory

In today's information age, high performance nonvolatile memory devices have become extremely important. Despite their potential, existing devices suffer from limitations, such as low operation speed, low memory capacity, short retention time, and a complex preparation process. To overcome these limitations, advanced memory designs are required to improve speed, memory capacity, and retention time and reduce the number of preparation steps. Here, we present a nonvolatile floating-gate-like memory device based on a transistor that uses the polarization effect of ferroelectric material PZT (Pb[Zr0.2Ti0.8]O3) for regulating tunneling electrons for charging and discharging the MoS2 channel layer. The transistor is defined as a polarized tunneling transistor (PTT) and does not require a tunnel layer or a floating-gate layer. The PTT demonstrates an ultrafast programming/erasing speed of 25/20 ns and a response time of 120/105 ns, which is comparable to the ultrafast flash memories based on van der Waals heterostructures. Additionally, the PTT has a high extinction ratio of 104, a long retention time of 10 years, and a simple fabrication process. Our research provides future guidelines for the development of the next generation of ultrafast nonvolatile memory devices.

Development of FAPI Tetramers to Improve Tumor Uptake and Efficacy of FAPI Radioligand Therapy.

Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) have shown promise as cancer diagnostic agents; however, the relatively short tumor retention of FAPIs may limit their application in radioligand therapy. In this paper, we report the design, synthesis, and evaluation of a FAPI tetramer. The aim of the study was to evaluate the tumor-targeting characteristics of radiolabeled FAPI multimers invitro and invivo, thereby providing information for the design of FAP-targeted radiopharmaceuticals based on the polyvalency principle. Methods: FAPI tetramers were synthesized on the basis of FAPI-46 and radiolabeled with 68Ga, 64Cu, and 177Lu. In vitro FAP-binding characteristics were identified using a competitive cell-binding experiment. To evaluate their pharmacokinetics, small-animal PET, SPECT, and ex vivo biodistribution analyses were performed on HT-1080-FAP and U87MG tumor-bearing mice. In addition, the 2 tumor xenografts received radioligand therapy with 177Lu-DOTA-4P(FAPI)4, and the antitumor efficacy of the 177Lu-FAPI tetramer was evaluated and compared with that of the 177Lu-FAPI dimer and monomer. Results: 68Ga-DOTA-4P(FAPI)4 and 177Lu-DOTA-4P(FAPI)4 were highly stable in phosphate-buffered saline and fetal bovine serum. The FAPI tetramer exhibited high FAP-binding affinity and specificity both invitro and invivo. 68Ga-, 64Cu-, and 177Lu-labeled FAPI tetramers exhibited higher tumor uptake, longer tumor retention, and slower clearance than FAPI dimers and FAPI-46 in HT-1080-FAP tumors. The uptake (percentage injected dose per gram) of 177Lu-DOTA-4P(FAPI)4, 177Lu-DOTA-2P(FAPI)2, and 177Lu-FAPI-46 in HT-1080-FAP tumors at 24 h was 21.4 ± 1.7, 17.1 ± 3.9, and 3.4 ± 0.7, respectively. Moreover, 68Ga-DOTA-4P(FAPI)4 uptake in U87MG tumors was approximately 2-fold the uptake of 68Ga-DOTA-2P(FAPI)2 (SUVmean, 0.72 ± 0.02 vs. 0.42 ± 0.03, P < 0.001) and more than 4-fold the uptake of 68Ga-FAPI-46 (0.16 ± 0.01, P < 0.001). In the radioligand therapy study, remarkable tumor suppression was observed with the 177Lu-FAPI tetramer in both HT-1080-FAP and U87MG tumor-bearing mice. Conclusion: The satisfactory FAP-binding affinity and specificity, as well as the favorable invivo pharmacokinetics of the FAPI tetramer, make it a promising radiopharmaceutical for theranostic applications. Improved tumor uptake and prolonged retention of the 177Lu-FAPI tetramer resulted in excellent characteristics for FAPI imaging and radioligand therapy.