Characteristics of the oral microbiota in patients with primary Sjögren's syndrome.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is an autoimmune disease with unknown etiology that is considered to be related to environmental and genetic factors. The aim of this study was to clarify the oral microflora characteristics of pSS patients and to reveal the connection between oral bacterial composition and dental caries using a high-throughput sequencing technique. METHODS: Thirty-five pSS patients and 20 healthy controls were enrolled in this study. We collected saliva and plaque samples from pSS patients and saliva samples from healthy controls. We used 16S ribosomal DNA (16S rDNA) high-throughput sequencing targeting the V3-V4 hypervariable region to determine the composition and structure of the microbiota in the three sample sets. Finally, bioinformatics analyses, including the diversity of the microbiota, species differences, and functional prediction were performed. RESULTS: In the alpha diversity and beta diversity analysis, the Chao1 (P < 0.01), observed species (P < 0.01), and PD whole tree indices (P < 0.01) were significantly lower in the saliva and plaque samples of pSS patients than in the saliva samples of healthy controls, but the Shannon (P < 0.01) and Simpson indices (P < 0.01) were significantly higher in the healthy controls, and their total diversity significantly differed. In the main flora composition at the genus level (top 10), we identified Prevotella and Veillonella as more enriched in the saliva of pSS patients and Fusobacterium, Actinomyces, and Leptotrichia as more enriched in the plaque of pSS patients. Predictive functional analysis showed that the oral microbiota of pSS patients was related to translation, metabolism of cofactors and vitamins, and nucleotide metabolism. CONCLUSIONS: The oral microbial ecology of patients with pSS is dysregulated, resulting in a decrease in overall diversity. Prevotella and Veillonella may be related to pSS, while Fusobacterium, Actinomyces, and Leptotrichia may be related to dental caries in pSS patients. Key Points • This study revealed differences in the oral microbial composition of patients with pSS compared to healthy controls. • We included a plaque group of pSS patients to identify the microbiota related to pSS and dental caries. • Prevotella and Veillonella may contribute to pSS, and Fusobacterium, Actinomyces, and Leptotrichia are associated with dental caries in pSS patients.

Increased Microbial Translocation is a Prognostic Biomarker of Different Immune Responses to ART in People Living with HIV.

Background: Microbial translocation (MT) is a characteristic of human immunodeficiency virus (HIV) infection. Whether MT is also a biomarker of different immune responses to antiretroviral therapy (ART) received by people living with HIV (PLWH) is not known. Methods: We examined the presence of MT in a cohort of 33 HIV-infected immunological responders (IRs) and 28 immunological non-responders (INRs) (≥500 and <200 cluster of differentiation (CD)4+ T-cell counts/µL after 2 years of HIV-1 suppression, respectively) with no comorbidities. Plasma samples were used to measure the circulating levels of MT markers. All enrolled study participants had received 2 years of viral-suppression therapy. Results: Levels of lipopolysaccharide (P = 0.0185), LPS-binding protein (P < 0.0001), soluble-CD14 (P < 0.0001), and endogenous endotoxin-core antibody (P < 0.0001) at baseline were significantly higher in INRs than in IRs and were associated with an increased risk of an immunological non-response, whereas the level of intestinal fatty acid-binding protein did not show this association. Analysis of receiver operating characteristic (ROC) curves demonstrated the utility of these individual microbial markers in discriminating INRs after ART in people living with HIV with high sensitivity, specificity, and area under the ROC curve. Conclusion: INRs in HIV infection are characterized by increased MT at baseline. These markers could be used as a rapid prognostic tool for predicting immune responses in people infected with the HIV.

Immune interference in effectiveness of influenza and COVID-19 vaccination.

Vaccines are known to function as the most effective interventional therapeutics for controlling infectious diseases, including polio, smallpox, rabies, tuberculosis, influenza and SARS-CoV-2. Smallpox has been eliminated completely and polio is almost extinct because of vaccines. Rabies vaccines and Bacille Calmette-Guérin (BCG) vaccines could effectively protect humans against respective infections. However, both influenza vaccines and COVID-19 vaccines are unable to eliminate these two infectious diseases of their highly variable antigenic sites in viral proteins. Vaccine effectiveness (VE) could be negatively influenced (i.e., interfered with) by immune imprinting of previous infections or vaccinations, and repeated vaccinations could interfere with VE against infections due to mismatch between vaccine strains and endemic viral strains. Moreover, VE could also be interfered with when more than one kind of vaccine is administrated concomitantly (i.e., co-administrated), suggesting that the VE could be modulated by the vaccine-induced immunity. In this review, we revisit the evidence that support the interfered VE result from immune imprinting or repeated vaccinations in influenza and COVID-19 vaccine, and the interference in co-administration of these two types of vaccines is also discussed. Regarding the development of next-generation COVID-19 vaccines, the researchers should focus on the induction of cross-reactive T-cell responses and naive B-cell responses to overcome negative effects from the immune system itself. The strategy of co-administrating influenza and COVID-19 vaccine needs to be considered more carefully and more clinical data is needed to verify this strategy to be safe and immunogenic.

Global, regional, and national HIV/AIDS disease burden levels and trends in 1990-2019: A systematic analysis for the global burden of disease 2019 study.

Background: Since the first HIV/AIDS case appeared in 1980s, HIV/AIDS has been the focus of international attention. As a major public health problem, there are epidemiological uncertainties about the future of HIV/AIDS. It is important to monitor the global statistics of HIV/AIDS prevalence, deaths, disability adjusted life years (DALYs), and risk factors for adequate prevention and control. Methods: The Global Burden of Disease Study 2019 database was used to analyze the burden of HIV/AIDS in 1990-2019. By extracting global, regional, and national data on HIV/AIDS prevalence, deaths, and DALYs, we described the distribution by age and sex, explored the risk factors, and analyzed the trends in HIV/AIDS. Results: In 2019, there were 36.85 million HIV/AIDS cases (95% UI: 35.15-38.86 million), 863.84 thousand deaths (95% UI: 78.61-99.60 thousand), and 47.63 million (95% UI: 42.63-55.65 million) DALYs. The global age-standardized HIV/AIDS prevalence, death, and DALY rates were 454.32 (95% UI: 433.76-478.59), 10.72 (95% UI: 9.70-12.39), and 601.49 (95% UI: 536.16-703.92) per 100,000 cases, respectively. In 2019, the global age-standardized HIV/AIDS prevalence, death, and DALY rates increased by 307.26 (95% UI: 304.45-312.63), 4.34 (95% UI: 3.78-4.90), and 221.91 (95% UI: 204.36-239.47) per 100,000 cases, respectively, compared to 1990. Age-standardized prevalence, death, and DALY rates decreased in high sociodemographic index (SDI) areas. High age-standardized rates were observed in low sociodemographic index areas, while low age-standardized rates were observed in high sociodemographic index areas. In 2019, the high age-standardized prevalence, death, and DALY rates were predominant in Southern Sub-Saharan Africa, and global DALYs peaked in 2004 and subsequently decreased. The highest global HIV/AIDS DALYs were in the 40-44 age group. The main risk factors affecting HIV/AIDS DALY rates included behavioral risks, drug use, partner violence, and unsafe sex. Conclusions: HIV/AIDS disease burden and risk factors vary by region, sex, and age. As access to health care increases across countries and treatment for HIV/AIDS infection improves, the HIV/AIDS disease burden is concentrated in areas with low SDIs, particularly in South Africa. Regional differences should be fully considered to target optimal prevention strategies and treatment options based on risk factors.

Activation of NRF2 blocks HIV replication and apoptosis in macrophages.

Abnormal oxidative stress caused by human immunodeficiency virus (HIV) infection affects viral replication and causes non-acquired immune deficiency syndrome-related complications in infected individuals. The transcription factor NFE2-related factor 2 (NRF2), a key regulator of oxidative stress, responds to abnormal oxidative stress by regulating the expression of NRF2-dependent cytoprotective genes. The present study aimed to determine whether inhibition of oxidative stress could control HIV replication and improve cell survival. In this study, the NRF2 activator, methyl bardoxolone, was used to treat cells for HIV infection. The effects on HIV replication and apoptosis pathways were confirmed by NRF2 activation or knockdown. The results showed that NRF2 activation could block HIV replication in macrophages before the integration phase and inhibited the expression of apoptotic pathways in virus-exposed macrophages. The study presents an unconventional anti-viral strategy of activation antioxidant response for HIV infection blocking.

Rapid identification of a major locus qPRL-C06 affecting primary root length in Brassica napus by QTL-seq.

BACKGROUND AND AIMS: Brassica napus is one of the most important oilseed crops worldwide. Seed yield of B. napus significantly correlates with the primary root length (PRL). The aims of this study were to identify quantitative trait loci (QTLs) for PRL in B. napus. METHODS: QTL-seq and conventional QTL mapping were jointly used to detect QTLs associated with PRL in a B. napus double haploid (DH) population derived from a cross between 'Tapidor' and 'Ningyou 7'. The identified major locus was confirmed and resolved by an association panel of B. napus and an advanced backcross population. RNA-seq analysis of two long-PRL lines (Tapidor and TN20) and two short-PRL lines (Ningyou 7 and TN77) was performed to identify differentially expressed genes in the primary root underlying the target QTLs. KEY RESULTS: A total of 20 QTLs impacting PRL in B. napus grown at a low phosphorus (P) supply were found by QTL-seq. Eight out of ten QTLs affecting PRL at a low P supply discovered by conventional QTL mapping could be detected by QTL-seq. The locus qPRL-C06 identified by QTL-seq was repeatedly detected at both an optimal P supply and a low P supply by conventional QTL mapping. This major constitutive QTL was further confirmed by regional association mapping. qPRL-C06 was delimited to a 0.77 Mb genomic region on chromosome C06 using an advanced backcross population. A total of 36 candidate genes within qPRL-C06 were identified that showed variations in coding sequences and/or exhibited significant differences in mRNA abundances in primary root between the long-PRL and short-PRL lines, including five genes involved in phytohormone biosynthesis and signaling. CONCLUSIONS: These results both demonstrate the power of the QTL-seq in rapid QTL detection for root traits and will contribute to marker-assisted selective breeding of B. napus cultivars with increased PRL.

Screening New Blood Indicators for Non-alcoholic Fatty Liver Disease (NAFLD) Diagnosis of Chinese Based on Machine Learning.

Background: The prevalence of NAFLD is increasing annually. The early diagnosis and control are crucial for the disease. Currently, metabolic indicators are always used clinically as an auxiliary diagnosis of NAFLD. However, the prevalence of NAFLD is not only increased in obese/metabolic-disordered populations. NAFLD patients with thin body are also increasing. Only using metabolic indicators to assist in the diagnosis of NAFLD may have some deficiencies. Continue to develop more clinical auxiliary diagnostic indicators is pressing. Methods: Machine learning methods are applied to capture risk factors for NAFLD in 365 adults from Zhejiang Province. Predictive models are constructed for NAFLD using fibrinolytic indicators and metabolic indicators as predictors respectively. Then the predictive effects are compared; ELISA kits were used to detect the blood indicators of non-NAFLD and NAFLD patients and compare the differences. Results: The prediction accuracy for NAFLD based on fibrinolytic indicators [Tissue Plasminogen Activator (TPA), Plasminogen Activator Inhibitor-1 (PAI-1)] is higher than that based on metabolic indicators. TPA and PAI-1 are more suitable than metabolic indicators to be selected to predict NAFLD. Conclusions: The fibrinolytic indicators have a stronger association with NAFLD than metabolic indicators. We should attach more importance to TPA and PAI-1, in addition to TC, HDL-C, LDL-C, and ALT/AST, when conducting blood tests to assess NAFLD.

Genetic Control of Seed Phytate Accumulation and the Development of Low-Phytate Crops: A Review and Perspective.

Breeding low phytic acid (lpa) crops is a strategy that has potential to both improve the nutritional quality of food and feed and contribute to the sustainability of agriculture. Here, we review the lipid-independent and -dependent pathways of phytate synthesis and their regulatory mechanisms in plants. We compare the genetic variation of the phytate concentration and distribution in seeds between dicot and monocot species as well as the associated temporal and spatial expression patterns of the genes involved in phytate synthesis and transport. Quantitative trait loci or significant single nucleotide polymorphisms for the seed phytate concentration have been identified in different plant species by linkage and association mapping, and some genes have been cloned from lpa mutants. We summarize the effects of various lpa mutations on important agronomic traits in crop plants and propose SULTR3;3 and SULTR3;4 as optimal target genes for lpa crop breeding.

Toxification metabolism and treatment strategy of the chiral triazole fungicide prothioconazole in water.

Toxification metabolism of the chiral triazole fungicide prothioconazole in the environment has attracted an increasing amount of attention. To better understand the fate of prothioconazole in aquatic ecosystems and develop a treatment strategy, the stereoselective toxicity, degradation and bioconcentration of prothioconazole were investigated in water with algae at the enantiomer level. There was remarkable enantioselectivity against Chlorella pyrenoidosa, and the highly toxic S-prothioconazole was preferentially degraded with enantiomer fraction values ranging from 0.5 to 0.74. Metabolism experiment results showed that the parent compound was quickly eliminated driven by biodegradation and abiotic degradation (hydrolysis, photolysis). Fourteen phase I and two phase II metabolites involved in the reactions of hydroxylation, methylation, dechlorinating, desulfuration, dehydration and conjugation were identified, where prothioconazole-desthio was the major metabolite. The highly toxic metabolite prothioconazole-desthio persisted in water and hardly degraded with or without C. pyrenoidosa. Furthermore, the reaction system including 1 mg of cobalt coated in nitrogen doped carbon nanotubes and 0.156 g of peroxymonosulfate was used to eliminate prothioconazole-desthio. Approximately 96% prothioconazole-desthio was eliminated and transformed to low toxicity metabolites. This work provides a strategy for the risk evaluation of prothioconazole in aquatic ecosystems and proposes a workable plan for the elimination of pesticide residues in water.

A Novel Dendrite-Free Lithium Metal Anode via Oxygen and Boron Codoped Honeycomb Carbon Skeleton.

Lithium (Li) metal is an excellent anode of Li ion batteries because of its high theoretical capacity and the low redox potential compared to other anodes. However, the uncontrollable growth of Li dendrites still incurs serious safety issues and poor electrochemical performances, leading to its limited practical application. An oxygen and boron codoped honeycomb carbon skeleton (OBHcCs) is reported and a stable Li metal-based anode is realized. It can be coated on a copper foil substrate to be used as a current collector for a dendrite-free Li metal anode. OBHcCs effectively reduces the local current density owing to the high surface area and inhibits Li dendrite growth, which is explored by scanning electron microscopy and an X-ray photoelectron spectra depth profile. The abundant lithiophilic oxygen and boron-containing functional groups reduce the potential barrier of nucleation and lead to the homogeneous Li ions flux as confirmed by the density functional theories. Therefore, the Li metal anode based on OBHcCs (OBHcCs@Li) stably runs for 700 h in a symmetric cell with a Li stripping capacity of 1 mAh cm-2 at 1 mA cm-2 . Furthermore, the OBHcCs@Li|LiFePO4 full cell shows a good capacity retention of 84.6% with a high coulombic efficiency of 99.6% at 0.5 C for 500 cycles.

Bimetallic phosphide AlP/SiP2 composite as an anode material for lithium-ion batteries with long cycle life.

AlP and SiP2 are promising alloy-type anode materials for lithium-ion batteries (LIBs), owing to their good conductivity, high storage capacity and appropriate working potential. However, they still suffer from rapid capacity decay due to the huge volume expansion and the resultant pulverization. Carbon modification can not only relieve volume changes but also provide a conducting matrix for the active material. Moreover, the charge transfer of the multi-phase composite can be accelerated owing to its electric field at the heterointerface. Hence, a bimetallic phosphide AlP/SiP2@C composite was synthesized for the first time via a facile and scalable high energy ball milling method and applied as an anode material for LIBs. Benefitting from the above combined advantages of the heterostructure and carbon layer protection, the AlP/SiP2@C electrode delivered a high reversible capacity (1482 mA h g-1 at the current density of 0.3 A g-1) and durable lifespan (516 mA h g-1 after 4000 cycles at a current density of 3 A g-1), which are superior to those of the binary AlP@C and SiP2@C composites.

Effects of strontium-incorporated micro/nano rough titanium surfaces on osseointegration via modulating polarization of macrophages.

Macrophages perform multiple functions in both inflammation and wound healing, and are one of the fore front cells during implant osseointegration that influence subsequent process. Essential trace element modification may effectively modulate titanium implant surface biological properties. In this work, strontium (Sr) incorporated micro/nano rough titanium surfaces (Sr-SLA) was fabricated by hydrothermal treatment, and immunoreaction of macrophages was further investigated. In vitro results revealed that Sr doping inhibited inflammatory response of macrophages, further attenuated the inhibitory effect on following bone marrow derived cells (BMSCs) osteogenic differentiation. The regulation of macrophages by Sr-SLA likely involved ERK signaling pathway. Consistently, the in vivo study showed that compared with titanium surface sand-blasted with large grit and double acid-etched (SLA) implants, Sr-SLA implants could enhance new bone formation accompanied with more alternatively activated M2 macrophages infiltration and less classically activated M1 macrophages infiltration. These results reveal the immunomodulatory ability of Sr-SLA of adjusting the functional status of macrophages through inhibiting M1 polarization while promoting M2 polarization.

Congenital renal arteriovenous malformation with cirsoid and cavernosal-type characteristics: a case report.

Renal arteriovenous malformations (AVMs) are infrequent vascular morphological anomalies. About 20% of AVMs are congenital renal AVMs (CRAVMs). A 53-year-old female patient presented with a 5-day history of gross hematuria and right flank pain. The patient underwent the selective renal arteriography and embolization under local anesthesia. Renal computed tomography angiography (CTA) and digital subtraction angiography (DSA) results showed bleeding of the right renal arteriovenous malformation, both nidus and aneurysm, which indicated that the patient had both cirsoid and cavernosal types of CRAVM. Endovascular management was chosen to treat the patient. The patient was cured and discharged, then followed-up for 3 months. These results show that early identification using radiologic tests is important for diagnosis and treatment of CRAVM.

Zinc- and strontium- co-incorporated nanorods on titanium surfaces with favorable material property, osteogenesis, and enhanced antibacterial activity.

Early infection and peri-implantitis after implant restoration are major reasons for dental implant failure. Implant-associated infections are majorly attributed to biofilm formation. In this study, co-incorporated zinc- (Zn-) and strontium- (Sr-) nanorod coating on sandblasted and acid-etched (SLA) titanium (SLA-Zn/Sr) was fabricated by hydrothermal synthesis. It was aimed at promoting osteogenesis while inhibiting biofilm formation. The nanorod-like particles (φ 30-50 nm) were found to be evenly formed on SLA-Zn/Sr (Zn: 1.49 ± 0.16 wt%; Sr: 21.69 ± 2.74 wt%) that was composed of well-crystallized ZnTiO3 and SrTiO3 phases. With a sufficient interface bonding strength (42.00 ± 3.00 MPa), SLA-Zn/Sr enhanced the corrosion resistance property of titanium. Besides, SLA-Zn/Sr promoted the cellular initial adhesion, proliferation and osteogenic differentiation of rBMSCs in vitro while inhibiting the adhesion of Staphylococcus aureus and Porphyromonas gingivalis . In addition, through down-regulating icaA gene expression, this novel surface reduced the secretion of polysaccharide intercellular adhesion (reduced by 87.9% compared to SLActive) to suppress the S. aureus biofilm formation. We, therefore, propose a new chemical modification on titanium for multifunctional implant material development. Due to the Zn/Sr co-doping in coating, material properties, early osteogenic effect and antibacterial ability of titanium can be simultaneously enhanced, which has the potential to be applied in dental implantation in the future.

Asymmetric Petasis reaction for the synthesis of chiral α- and ß-butadienyl amines.

The Petasis reaction using (1S,2R)-1-amino-2-indanol as the substrate and an activator to construct α- and ß-butadienyl amines in optically pure forms was realized, which are otherwise difficult to prepare. The reactions feature a metal-free nature, broad substrate scope, complete regioselectivities (γ-selectivity of pinacol homoallenyl- and isoprenylboronates), and high to excellent chirality induction (up to >20 : 1 dr). The favored nucleophilic addition across the Si-face of the imine intermediate was explained using DFT calculations of the six-membered chair-like transition state.

Identification of a prognostic gene signature of colon cancer using integrated bioinformatics analysis.

BACKGROUND: Colon cancer is a worldwide leading cause of cancer-related mortality, and the prognosis of colon cancer is still needed to be improved. This study aimed to construct a prognostic model for predicting the prognosis of colon cancer. METHODS: The gene expression profile data of colon cancer were obtained from the TCGA, GSE44861, and GSE44076 datasets. The WGCNA module genes and common differentially expressed genes (DEGs) were used to screen out the prognosis-associated DEGs, which were used to construct a prognostic model. The performance of the prognostic model was assessed and validated in the TCGA training and microarray validation sets (GSE38832 and GSE17538). At last, the model and prognosis-associated clinical factors were used for the construction of the nomogram. RESULTS: Five colon cancer-related WGCNA modules (including 1160 genes) and 1153 DEGs between tumor and normal tissues were identified, inclusive of 556 overlapping DEGs. Stepwise Cox regression analyses identified there were 14 prognosis-associated DEGs, of which 12 DEGs were included in the optimized prognostic gene signature. This prognostic model presented a high forecast ability for the prognosis of colon cancer both in the TCGA training dataset and the validation datasets (GSE38832 and GSE17538; AUC > 0.8). In addition, patients' age, T classification, recurrence status, and prognostic risk score were associated with the prognosis of TCGA patients with colon cancer. The nomogram was constructed using the above factors, and the predictive 3- and 5-year survival probabilities had high compliance with the actual survival proportions. CONCLUSIONS: The 12-gene signature prognostic model had a high predictive ability for the prognosis of colon cancer.

A Genetically Encoded RNA Photosensitizer for Targeted Cell Regulation.

Genetically encoded RNA devices have emerged for various cellular applications in imaging and biosensing, but their functions as precise regulators in living systems are still limited. Inspired by protein photosensitizers, we propose here a genetically encoded RNA aptamer based photosensitizer (GRAP). Upon illumination, the RNA photosensitizer can controllably generate reactive oxygen species for targeted cell regulation. The GRAP system can be selectively activated by endogenous stimuli and light of different wavelengths. Compared with their protein analogues, GRAP is highly programmable and exhibits reduced off-target effects. These results indicate that GRAP enables efficient noninvasive target cell ablation with high temporal and spatial precision. This new RNA regulator system will be widely used for optogenetics, targeted cell ablation, subcellular manipulation, and imaging.

[Efficacy and safety of letrozole in treatment of McCune-Albright syndrome girls with peripheral precocious puberty].

OBJECTIVE: To evaluate the efficacy and safety of the third-generation aromatase inhibitor letrozole in the treatment of McCune-Albright syndrome (MAS) girls with peripheral precocious puberty. METHODS: Twenty-one MAS girls with peripheral precocious puberty treated in Pediatrics Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2012 to June 2017 were enrolled in the study. Patients presented with repeated vaginal bleeding, premature breast enlargement, café-au-lait spots or dysplasia of bone fibers, and low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH); and the congenital adrenal hyperplasia, estrogen-producing tumors, and exogenous estrogen intake were excluded. Letrozole were administrated at a dose of 0.5-2 mg·m -2·d -1 for 6 to 12 months. The patients were observed for changes in breast staging, vaginal bleeding, sex hormone levels, liver function and bone age changes, and changes in uterine and ovarian volume. RESULTS: After treatment, bone age/chronological age (BA/CA)was decreased from 1.23±0.30 to 1.11±0.18 ( P < 0.01); the predicted adult height (PAH) increased from (156.2±5.9)cm to (158.4±2.1)cm after treatment ( P < 0.05); the vaginal bleeding was reduced and the estradiol level decreased, while the teststosterone level and the uterus showed no significant increase, and no adverse reactions such as ovarian torsion and abnormal liver function were observed. CONCLUSIONS: Precocious puberty is one of the most common endocrine manifestations in MAS. Our findings suggest that letrozole may be an effective and safe therapy to precocious puberty in girls with McCune-Albright Syndrome.

In Situ Genetically Cascaded Amplification for Imaging RNA Subcellular Locations.

In situ amplification methods, such as hybridization chain reaction, are valuable tools for mapping the spatial distribution and subcellular location of target analytes. However, the live-cell applications of these methods are still limited due to challenges in the probe delivery, degradation, and cytotoxicity. Herein, we report a novel genetically encoded in situ amplification method to noninvasively image the subcellular location of RNA targets in living cells. In our system, a fluorogenic RNA reporter, Broccoli, was split into two nonfluorescent fragments and conjugated to the end of two RNA hairpin strands. The binding of one target RNA can then trigger a cascaded hybridization between these hairpin pairs and thus activate multiple Broccoli fluorescence signals. We have shown that such an in situ amplified strategy can be used for the sensitive detection and location imaging of various RNA targets in living bacterial and mammalian cells. This new design principle provides an effective and versatile platform for tracking various intracellular analytes.

Battery-free, lightweight, injectable microsystem for in vivo wireless pharmacology and optogenetics.

Pharmacology and optogenetics are widely used in neuroscience research to study the central and peripheral nervous systems. While both approaches allow for sophisticated studies of neural circuitry, continued advances are, in part, hampered by technology limitations associated with requirements for physical tethers that connect external equipment to rigid probes inserted into delicate regions of the brain. The results can lead to tissue damage and alterations in behavioral tasks and natural movements, with additional difficulties in use for studies that involve social interactions and/or motions in complex 3-dimensional environments. These disadvantages are particularly pronounced in research that demands combined optogenetic and pharmacological functions in a single experiment. Here, we present a lightweight, wireless, battery-free injectable microsystem that combines soft microfluidic and microscale inorganic light-emitting diode probes for programmable pharmacology and optogenetics, designed to offer the features of drug refillability and adjustable flow rates, together with programmable control over the temporal profiles. The technology has potential for large-scale manufacturing and broad distribution to the neuroscience community, with capabilities in targeting specific neuronal populations in freely moving animals. In addition, the same platform can easily be adapted for a wide range of other types of passive or active electronic functions, including electrical stimulation.