Competitive enrichment of comammox Nitrospira in floccular sludge.

The discovery of complete ammonium oxidation (comammox) has subverted the traditional perception of two-step nitrification, which plays a key role in achieving biological nitrogen removal from wastewater. Floccular sludge-based treatment technologies are being applied at the majority of wastewater treatment plants in service where detection of various abundances and activities of comammox bacteria have been reported. However, limited efforts have been made to enrich and subsequently characterize comammox bacteria in floccular sludge. To this end, a lab-scale sequencing batch reactor (SBR) in the step-feeding mode was applied in this work to enrich comammox bacteria through controlling appropriate operational conditions (dissolved oxygen of 0.5 ± 0.1 g-O2/m3, influent ammonium of 40 g-N/m3 and uncontrolled longer sludge retention time). After 215-d operation, comammox bacteria gradually gained competitive advantages over counterparts in the SBR with a stable nitrification efficiency of 92.2 ± 2.2 %: the relative abundance of Nitrospira reached 42.9 ± 1.3 %, which was 13 times higher than that of Nitrosomonas, and the amoA gene level of comammox bacteria increased to 7.7 ± 2.1 × 106 copies/g-biomass, nearly 50 times higher than that of conventional ammonium-oxidizing bacteria. The enrichment of comammox bacteria, especially Clade A Candidatus Nitrospira nitrosa, in the floccular sludge led to (i) apparent affinity constants for ammonium and oxygen of 3.296 ± 0.989 g-N/m3 and 0.110 ± 0.004 g-O2/m3, respectively, and (ii) significantly low N2O and NO production, with emission factors being 0.136 ± 0.026 % and 0.023 ± 0.013 %, respectively.

Impact of coronavirus disease 2019 (COVID-19) on antimicrobial resistance among major pathogens causing healthcare-associated infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused great impact on healthcare systems, including antibiotic usage and multi-drug resistant (MDR) bacterial infections at hospitals. We aim to investigate the trends of antimicrobial resistance among the major pathogens causing healthcare-associated infection (HAI) at intensive care units (ICU). MATERIAL AND METHODS: The demographic characteristics of hospitalization, usage of antimicrobial agents, counted by half-an-year DID (defined daily dose per 1000 patient-days), and HAI density of five major MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), of ICU patients at a medical center in Taiwan during January 2017 to December 2021 were collected and analyzed. RESULTS: The total antibiotic usage, counted by DID, had a significant increasing trend, before COVID-19 occurrence in 2017-2019, but no further increase during the pandemic period in 2020-2021. However, comparing the two time periods, antibiotics consumption was significantly increased during pandemic period. There was no significant change of HAI density in MRSA, VRE, CRAB, CRKP, and CRPA, comparing the pandemic to the pre-pandemic period. Although, CRKP and CRPA infection rates were increasing during the pre-pandemic period, there was no further increase of CRKP and CRPA HAI rates during the pandemic period. CONCLUSION: During COVID-19 pandemic, there was no significant increase in HAI density of five major MDR bacteria at ICU in Taiwan, despite increased antibiotic usage. Strict infection prevention measures for COVID-19 precautions and sustained antimicrobial stewardship probably bring these effects.

Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.

PURPOSE: Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. PATIENTS AND METHODS: This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. RESULTS: We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm (P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm (P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). CONCLUSION: HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

Evaluation of different 16S rRNA gene hypervariable regions and reference databases for profiling engineered microbiota structure and functional guilds in a swine wastewater treatment plant.

High-throughput 16S rRNA gene amplicon sequencing technology is widely applied for environmental microbiota structure analysis to derive knowledge that informs microbiome-based surveillance and oriented bioengineering. However, it remains elusive how the selection of 16S rRNA gene hypervariable regions and reference databases affects microbiota diversity and structure profiling. This study systematically evaluated the fitness of different frequently used reference databases (i.e. SILVA 138 SSU, GTDB bact120_r207, Greengenes 13_5 and MiDAS 4.8) and primers of 16S rRNA gene in microbiota profiling of anaerobic digestion and activated sludge collected from a full-scale swine wastewater treatment plant (WWTP). The comparative results showed that MiDAS 4.8 achieved the highest levels of taxonomic diversity and species-level assignment rate. For whichever sample groups, microbiota richness captured by different primers decreased in the following order: V4 > V4-V5 > V3-V4 > V6-V8/V1-V3. Using primer-bias-free metagenomic data results as the judging standard, V4 region also best characterized microbiota structure and well represented typical functional guilds (e.g. methanogens, ammonium oxidizers and denitrifiers), while V6-V8 regions largely overestimated the archaeal methanogens (mainly Methanosarcina) by over 30 times. Therefore, MiDAS 4.8 database and V4 region are recommended for best simultaneous analysis of bacterial and archaeal community diversity and structure of the examined swine WWTP.

Microbiome assembly mechanism and functional potential in enhanced biological phosphorus removal system enriched with Tetrasphaera-related polyphosphate accumulating organisms.

Tetrasphaera-related polyphosphate accumulating organisms (PAOs) are the key functional guilds for enhanced biological phosphorus removal (EBPR) systems. Their biomass enrichment can be enhanced by the nitrification inhibitor allylthiourea (ATU). However, the underlying assembly mechanism and the functional potential of the EBPR microbiome regulated by ATU are unclear. This study investigates the effect of ATU on microbiome assembly and functional potential by closely following the microbiota dynamics in an EBPR system enriched with Tetrasphaera-related PAOs for 288-days before, during and after ATU addition. The results showed that ATU addition increased microbiota structural similarity and compositional convergence, and enhanced determinism in the assembly of EBPR microbiome. During exposure to ATU, Tetrasphaera-related PAOs were governed by homogeneous selection and the dominant species revealed by 16S rRNA gene-based phylogenetic analysis shifted from clade III to clade I. Meanwhile, ATU supply promoted significant enrichment of functional genes involved in phosphate transport (pit) and polyphosphate synthesis and degradation (ppk1 and ppk2), whereas both Nitrosomonas and ammonia monooxygenase-encoding genes (amoA/B/C) assignable to this group of nitrifying bacteria decreased. Moreover, ATU addition relieved the significant abundance correlation between filamentous bacteria Ca. Promineofilum and denitrifying Brevundimonas (FDR-adjusted P < 0.01), damaging their potential synergic or cooperative interactions, thus weakening their competitiveness against Tetrasphaera-related PAOs. Notably, ATU withdrawn created opportunistic conditions for the unexpected explosive growth and predominance of Thiothrix filaments, leading to a serious bulking event. Our study provides new insights into the microbial ecology of Tetrasphaera-related PAOs in EBPR system, which could guide the establishment of an efficient microbiota for EBPR.

Automatic tube compensation for liberation from prolonged mechanical ventilation in tracheostomized patients: A retrospective analysis.

BACKGROUND: To analyze the predictability of an automatic tube compensation (ATC) screening test compared with the conventional direct liberation test performed before continuous oxygen support for MV liberation. METHODS: This retrospective study analyzed tracheostomized patients with prolonged MV in a weaning unit of a medical center in Taiwan. In March 2020, a four-day ATC test to screen patient eligibility for ventilator liberation was implemented, intended to replace the direct liberation test. We compared the predictive accuracy of these two screening methods on the relevant outcomes in the two years before and one year after the implementation of this policy. RESULTS: Of the 403 cases, 246 (61%) and 157 (39%) received direct liberation and ATC screening tests, respectively. These two groups had similar outcomes: successful weaning upon leaving the Respiratory Care Center (RCC), success on day 100 of MV, success at hospital discharge, and in-hospital survival. Receiver operating characteristic curve analysis showed that the ATC screening test had better predictive ability than the direct liberation test for RCC weaning, discharge weaning, 100-day weaning, and in-hospital survival. CONCLUSION: This closed-circuit ATC screening test before ventilator liberation is a feasible and valuable method for screening PMV patients undergoing ventilator liberation in the pandemic era. Its predictability for a comparison with the open-circuit oxygen test requires further investigation.

Monitoring the performance of a dedicated weaning unit using risk-adjusted control charts for the weaning rate in prolonged mechanical ventilation.

BACKGROUND: Weaning rate is an important quality indicator of care for patients with prolonged mechanical ventilation (PMV). However, diverse clinical characteristics often affect the measured rate. A risk-adjusted control chart may be beneficial for assessing the quality of care. METHODS: We analyzed patients with PMV who were discharged between 2018 and 2020 from a dedicated weaning unit at a medical center. We generated a formula to estimate monthly weaning rates using multivariate logistic regression for the clinical, laboratory, and physiologic characteristics upon weaning unit admission in the first two years (Phase I). We then applied both multiplicative and additive models for adjusted p-charts, displayed in both non-segmented and segmented formats, to assess whether special cause variation existed. RESULTS: A total of 737 patients were analyzed, including 503 in Phase I and 234 in Phase II, with average weaning rates of 59.4% and 60.3%, respectively. The p-chart of crude weaning rates did not show special cause variation. Ten variables from the regression analysis were selected for the formula to predict individual weaning probability and generate estimated weaning rates in Phases I and II. For risk-adjusted p-charts, both multiplicative and additive models showed similar findings and no special cause variation. CONCLUSION: Risk-adjusted control charts generated using a combination of multivariate logistic regression and control chart-adjustment models may provide a feasible method to assess the quality of care in the setting of PMV with standard care protocols.

Prevalence and Significance of Antinuclear Antibodies in Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Aim: Associations between antinuclear antibodies (ANAs) and disease severity in nonalcoholic fatty liver disease (NAFLD) remain unclear. This study aimed to provide reliable estimates of ANA prevalence in subjects with biopsy-proven NAFLD and to investigate whether its associations with liver disease severity were established. Methods: Observational studies measuring ANA in NAFLD patients were derived from the PubMed, Embase, and Web of Science databases from inception to March 30, 2022. The effect size was presented as the pooled risk difference, unstandardized mean differences (MDs), and odds ratio (OR) with a 95% confidence interval (CI). Results: Thirteen articles involving 2331 patients were finally included. Among the subjects with biopsy-proven NAFLD, the overall prevalence of ANA positivity was high as 23% (95% CI: 19%-28%), but there were no statistically significant differences between ANA-positive and ANA-negative NAFLD patients in the levels of liver enzymes and blood lipids, grades of hepatocellular ballooning, lobular and portal inflammation, or risks of moderate-severe steatosis and significant fibrosis. However, the subgroup analysis showed that different geographic regions led to diverse results. ANA positivity was associated with a significantly elevated risk of significant fibrosis in the Eastern population (OR = 2.30, 95% CI: 1.30-4.06) but not in the Western population (OR = 1.00, 95% CI: 0.54-1.83). Conclusions: Serum ANA was present in approximately one-quarter of subjects with biopsy-proven NAFLD, but it conferred a greater risk of significant fibrosis only in Eastern but not Western populations.

Adaptation and evolution of freshwater Anammox communities treating saline/brackish wastewater.

The most common way to apply Anammox for saline wastewater treatment is via salt adaptation of freshwater Anammox bacteria (FAB). To better apply this process in practice, it's essential to understand the salt adaptation process of FBA, as well as the underlying mechanisms. This study investigated the long-term salt adaptation process of a fixed-film FAB culture in three reactors (namely R1-R3), under salinities of 2, 8, and 12 NaCl g/L, correspondingly. All three reactors were under stable operation and achieved 80-90% total inorganic nitrogen removal efficiency throughout the 425-day operation period. R1 servers as a blank control, based on the clear microbial community shifts in R2 and R3, the operation period was divided into 2 phases. During Phase 1, all FAB in the three reactors belonged to Ca. Brocadia sp.. The Anammox activity (AA) and the ratio of nitrite/ammonium (NO2--N/NH4+-N) consumption in R2 and R3 decreased with the increase of salinity and did not recover to the initial levels. During Phase 2, the relative abundance of Ca. Kuenenia sp. in R2 and R3 increased from nearly 0 to about 60 and 77%, respectively. With the growth of Ca. Kuenenia sp., the AA and stoichiometry of R2 and R3 gradually recovered. AA of R2 and R3 both reached 1.0 g NH4+-N/L/day at the end of this phase, which was about 80% of that in R1. These results indicated that the salt adaptation of FAB culture was achieved by species shift from a low salt-tolerance one to a high salt-tolerance one.

The complete chloroplast genome of Alsophila latebrosa, a common and widespread tree fern (Cyatheaceae).

Alsophila latebrosa is a common and widespread tree fern of Cyatheaceae. Its complete chloroplast genome is first assembled and reported with 155,724 bp in length, including a large single copy (LSC) region of 85,800 bp, a small single copy (SSC) region of 21,620 bp, and a pair of inverted repeats (IRs) of 24,152 bp. The genome has 133 genes, including 89 protein-coding genes, 33 tRNA genes, eight rRNA genes and three pseudogenes. Maximum likelihood approach was employed to construct the phylogenetic relationship among ten ferns including A. latebrosa. The result showed that A. latebrosa was most related to A. costularis as a sister group with 100% bootstrap support. The complete chloroplast genome sequences of A. latebrosa will provide valuable genomic information to further illuminate phylogenetic classification of Cyatheacea.

Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study.

PURPOSE: Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS: We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS: We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group (P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group (P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION: Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.

Update and review of the gerodontology prospective for 2020's: Linking the interactions of oral (hypo)-functions to health vs. systemic diseases.

New lines of evidence suggest that the oral-systemic medical links and oral hypo-function are progressively transcending beyond the traditional clinical signs and symptoms of oral diseases. Research into the dysbiotic microbiome, host immune/inflammatory regulations and patho-physiologic changes and subsequent adaptations through the oral-systemic measures under ageism points to pathways leading to mastication deficiency, dysphagia, signature brain activities for (neuro)-cognition circuitries, dementia and certain cancers of the digestive system as well. Therefore, the coming era of oral health-linked systemic disorders will likely reshape the future of diagnostics in oral geriatrics, treatment modalities and professional therapies in clinical disciplines. In parallel to these highlights, a recent international symposium was jointly held by the International Association of Gerontology and Geriatrics (IAGG), Japanese Society of Gerodontology (JSG), the representative of USA and Taiwan Academy of Geriatric Dentistry (TAGD) on Oct 25th, 2019. Herein, specific notes are briefly addressed and updated for a summative prospective from this symposium and the recent literature.

Targeting miR-21 with NL101 blocks c-Myc/Mxd1 loop and inhibits the growth of B cell lymphoma.

Background: NL101 has shown activities against multiple myeloma and acute myeloid leukemia, but its anti-lymphoma activity remains unknown. The transcription factor c-Myc is frequently dysregulated in aggressive B cell lymphomas such as double-hit lymphoma, for which the standard of care is still lacking. A novel approach to target c-Myc needs to be explored. Although the role of oncogenic microRNA-21 (miR-21) was well established in an inducible mice model of B cell lymphoma, whether targeting miR-21 could inhibit the growth of B cell lymphoma and its underlying mechanisms is unclear. Methods: We used MTT assay and flow cytometry to determine the inhibitory effect of NL101 on the cell proliferation of B cell lymphoma in vitro. The lymphoma xenograft mice models were generated to evaluate the anti-lymphoma function in vivo. Western blot and qPCR were applied to measure the expression levels of protein and microRNA, respectively. To investigate the mechanisms of action in NL101, we used genechip to profile differentially-expressed genes upon NL101 induction. Luciferase reporter system and chromatin immunoprecipitation were used for the validation of target gene or miRNA. Results: Nl101 significantly inhibited B cell lymphoma proliferation through induction of cell cycle arrest and apoptosis. NL101 suppressed the growth of B cell lymphoma in vivo and prolonged the survival of lymphoma xenograft models. Gene expression profiling revealed that miR-21 was significantly decreased upon the induction of NL101 in B cell lymphoma. The miR-21 level was associated with the sensitivity of NL101. miR-21 inhibited Mxd1 expression via directly combining to Mxd1 3'-UTR; c-Myc activated miR-21 expression by directly binding to the miR-21 promoter. Conclusion: NL101 significantly inhibited the growth of B cell lymphoma in vitro and in vivo. The novel c-Myc/miR-21/Mxd1 positive-feedback loop is critical for the maintenance of B cell lymphoma survival. Targeting miR-21 to block c-Myc/miR-21/Mxd1 loop represents a novel potential strategy of c-Myc-directed therapy.

Small nucleolar RNA is potential as a novel player in leukemogenesis and clinical application.

Lack of clarity of the mechanisms that underlie leukemogenesis obstructs the diagnosis, prognosis, and treatment of leukemia. Research has found that small nuclear RNA (snoRNA) plays an essential role in leukemia. These small non-coding RNAs are involved in ribosome biogenesis, including the 2'-O-methylation and pseudouridylation of precursor ribosomal RNA (pre-rRNA), and pre-rRNA splicing. Recently, many snoRNAs were found to be orphans that have no predictable RNA modification targets, but these RNAs have always been found to be located in different subcellular organelles, and they play diverse roles. Using high-throughput technology, snoRNA expression profiles have been revealed in leukemia, and some of the deregulated snoRNAs may regulate the cell cycle, differentiation, proliferation, and apoptosis in leukemic cells and confer drug resistance during leukemia treatment. In this review, we discuss the expression profiles and functions of snoRNAs, particularly orphan snoRNAs, in leukemia. It is possible that the dysregulated snoRNAs are promising diagnosis and prognosis markers for leukemia, which may serve as potential therapeutic targets in leukemia treatment.

Salinity effect on freshwater Anammox bacteria: Ionic stress and ion composition.

The biggest challenge to apply Anammox to treat wastewater with elevated salt content is the inhibitory effect of salinity on freshwater Anammox bacteria (FAB). Most of the research into salinity inhibition has focused on the osmotic pressure effect, while the inhibitory effect and its mechanisms induced by ion composition are poorly understood. In this study, the individual and combined effect of NaCl, KCl and Na2SO4 on FAB (>99% belonging to Ca. Brocadia genera) were systematically investigated by batch tests. The corresponding responses of mRNA abundance of three functional genes (including nitrite reductase gene (nirS), hydrazine synthase gene (hzsB) and hydrazine dehydrogenase gene (hdh)) under different salt conditions were analyzed. The results indicated that NaCl, KCl and Na2SO4 have different inhibition effects, with the 50% inhibition at 0.106, 0.096 and 0.063 M, respectively. The combined inhibition of NaCl+KCl and NaCl+Na2SO4 on FAB were both synergistic; while the combined inhibition of NaCl+KCl+Na2SO4 was additive. The responses of mRNA (of genes: nirS, hzsB and hdh) suggested NaCl inhibited the transport of ammonium; Na2SO4 inhibited both nitrite and ammonium transport; high salinity inhibited functional enzyme activity. These results suggest both ionic stress and ion composition contributed to the observed inhibition.

Individual and combined effect of salinity and nitrite on freshwater Anammox bacteria (FAB).

Anaerobic ammonium oxidation (Anammox) based technology has potential for nitrogen removal from wastewater with high salinity, but both salt and nitrite (a substrate for Anammox) have negative effect on microbial activity. In order to achieve Anammox in saline wastewater treatment, it is essential to understand the combined effect of these two components. In this study, the individual and combined effect of salinity and nitrite on fixed film freshwater Anammox bacteria (FAB, mainly belonging to the Ca. Brocadia genus), enriched on carriers from a 1500 L pilot scale one-stage (PN/Anammox) moving bed bioreactor (MBBR), were systematically investigated by 57 pre-designed batch tests. The combined inhibition of nitrite and salinity was determined by comparing with additive and independent inhibition models. With salinity only, the specific Anammox activity (SAA) decreased with increasing salinity: 14.6 mS/cm (about 9.1 g NaCl/L) of salinity caused 50% inhibition (IC50). With nitrite only, SAA started to decrease when nitrite concentration was above 450 mg N/L (threshold) and decreased with increased nitrite (IC50 = 666 mg N/L) thereafter. Significantly, when both salinity and nitrite were elevated, both the threshold and IC50 of nitrite were reduced, with inhibition enhanced. Analysis showed that at high salinity (>14.6 mS/cm) and nitrite concentration (>666 mg N/L), inhibition was close to that predicted by simulation of additive and independent inhibition models. Within a salinity range of 4-14.6 mS/cm and nitrite concentration range of 50-666 mg N/L, the combined inhibition was more severe than prediction (p < 0.05) based on the additive and independent inhibition models and therefore it was determined to be synergistic inhibition.

Perturbative countersurveillance metaoptics with compound nanosieves.

The progress of metaoptics relies on identifying photonic materials and geometries, the combination of which represents a promising approach to complex and desired optical functionalities. Material candidate options are primarily limited by natural availability. Thus, the search for meta-atom geometries, by either forward or inverse means, plays a pivotal role in achieving more sophisticated phenomena. Past efforts mainly focused on building the geometric library of individual meta-atoms and synthesizing various ones into a design. However, those efforts neglected the powerfulness of perturbative metaoptics due to the perception that perturbations are usually regarded as adverse and in need of being suppressed. Here, we report a perturbation-induced countersurveillance strategy using compound nanosieves mediated by structural and thermal perturbations. Private information can be almost perfectly concealed and camouflaged by the induced thermal-spectral drifts, enabling information storage and exchange in a covert way. This perturbative metaoptics can self-indicate whether the hidden information has been attacked during delivery. Our results establish a perturbative paradigm of securing a safer world of information and internet of things.

Compounding Plasmon⁻Exciton Strong Coupling System with Gold Nanofilm to Boost Rabi Splitting.

Various plasmonic nanocavities possessing an extremely small mode volume have been developed and applied successfully in the study of strong light-matter coupling. Driven by the desire of constructing quantum networks and other functional quantum devices, a growing trend of strong coupling research is to explore the possibility of fabricating simple strong coupling nanosystems as the building blocks to construct complex systems or devices. Herein, we investigate such a nanocube-exciton building block (i.e. AuNC@J-agg), which is fabricated by coating Au nanocubes with excitonic J-aggregate molecules. The extinction spectra of AuNC@J-agg assembly, as well as the dark field scattering spectra of the individual nanocube-exciton, exhibit Rabi splitting of 100⁻140 meV, which signifies strong plasmon⁻exciton coupling. We further demonstrate the feasibility of constructing a more complex system of AuNC@J-agg on Au film, which achieves a much stronger coupling, with Rabi splitting of 377 meV. This work provides a practical pathway of building complex systems from building blocks, which are simple strong coupling systems, which lays the foundation for exploring further fundamental studies or inventing novel quantum devices.

Bp-Bs, a Novel T-cell Engaging Bispecific Antibody with Biparatopic Her2 Binding, Has Potent Anti-tumor Activities.

Patients with Human epidermal growth factor receptor type 2 (Her2) overexpression are associated with aggressive tumor growth and poor clinical outcomes. Bispecific antibodies targeting Her2 have recently exhibited potent effects on Her2 signal inhibition. In this study, a novel biparatopic anti-Her2 bispecific antibody (Bp-Bs) was constructed by linking a single anti-CD3 Fab with two different anti-Her2 single-domain antibodies targeting non-overlapping epitopes of Her2. The Bp-Bs demonstrated strong binding on Her2-positive cells and potent cytotoxicity on Her2-positive tumor cells, even Her2-low expression cells, suggesting that biparatopic bispecific antibodies may have improved therapeutic benefits on broad Her2 patient populations.

Characterization of a highly specific monoclonal antibody against human aldo-keto reductase AKR1C3.

Human aldo-keto reductase AKR1C3 (type 2 3α-hydroxysteroid dehydrogenase/type 5 17ß-hydroxysteroid dehydrogenase) is involved in testosterone and estrogen metabolism. AKR1C3 expression is relatively low in most tissues and high in prostate and mammary glands in regulating androgen and estrogen levels. However, in many cancers, overexpression of AKR1C3 was observed, thus prompting the development of therapeutics targeting AKR1C3. To facilitate the development of AKR1C3 targeting therapeutics, evaluating the expression of AKR1C3 is vital. As AKR1C3 is highly homologous with its family proteins, AKR1C1, AKR1C2, AKR1C4 and other AKR1 proteins, reagents that can unambiguously discriminate these enzymes are needed. In this report, a highly specific monoclonal antibody for AKR1C3, 10B10, was developed and characterized. Compared to other AKR1C3 antibodies, 10B10 is highly specific and sensitive to AKR1C3 in multiple assay formats. Thus, 10B10 will be a valuable tool for the clinical development of AKR1C3 targeting therapeutics and the study of AKR1C3 biology.