Fabrication of red-emitting perovskite LEDs by stabilizing their octahedral structure.

Light-emitting diodes (LEDs) based on metal halide perovskites (PeLEDs) with high colour quality and facile solution processing are promising candidates for full-colour and high-definition displays1-4. Despite the great success achieved in green PeLEDs with lead bromide perovskites5, it is still challenging to realize pure-red (620-650 nm) LEDs using iodine-based counterparts, as they are constrained by the low intrinsic bandgap6. Here we report efficient and colour-stable PeLEDs across the entire pure-red region, with a peak external quantum efficiency reaching 28.7% at 638 nm, enabled by incorporating a double-end anchored ligand molecule into pure-iodine perovskites. We demonstrate that a key function of the organic intercalating cation is to stabilize the lead iodine octahedron through coordination with exposed lead ions and enhanced hydrogen bonding with iodine. The molecule synergistically facilitates spectral modulation, promotes charge transfer between perovskite quantum wells and reduces iodine migration under electrical bias. We realize continuously tunable emission wavelengths for iodine-based perovskite films with suppressed energy loss due to the decrease in bond energy of lead iodine in ionic perovskites as the bandgap increases. Importantly, the resultant devices show outstanding spectral stability and a half-lifetime of more than 7,600 min at an initial luminance of 100 cd m-2.

Impact of Hypoxia-Inducible Factor-1α on Host Immune Metabolism and Tissue Damage During Mycobacterium bovis Infection.

HIF-1α is a pivotal regulator of metabolic and inflammatory responses. This study investigated the role of HIF-1α in M. bovis infection and its effects on host immune metabolism and tissue damage. We evaluated the expression of immunometabolism markers and MMPs infected with M. bovis, and following HIF-1α inhibition in vitro. To understand the implications of HIF-1α inhibition on disease progression, mice at different infection stages were treated with the HIF-1α inhibitor, YC-1. Our results revealed an upregulation of the HIF-1α in macrophages post-M. bovis infection, facilitating enhanced M1 macrophage polarization. The blockade of HIF-1α moderated these responses but escalated MMP activity, hindering bacterial control. Consistent with our in vitro results, early-stage treatment of mice with YC-1 aggravated pathological alterations and tissue damage, while late-stage HIF-1α inhibition proved beneficial in managing the disease. Overall, our findings underscored the nuanced role of HIF-1α across varying phases of M. bovis infection.

The bacterial patterns suggesting the dynamic features of tick-associated microorganisms in hard ticks.

BACKGROUND: Ticks are blood-feeding significant arthropods that can harbour various microorganisms, including pathogens that pose health risks to humans and animals. Tick-symbiont microorganisms are believed to influence tick development, but the intricate interactions between these microbes and the relationships between different tick-borne microorganisms remain largely unexplored. RESULTS: Based on 111 tick pool samples presenting questing and engorged statuses including 752 questing tick and 1083 engorged tick from cattle and goats, which were collected in two types of geographic landscape (semi-desert and alpine meadow). We observed significant variations in the composition of tick-borne microorganisms across different environments and blood-engorgement statuses, with a pronounced divergence in symbionts compared to environmental bacteria. Metabolic predictions revealed over 90 differential pathways for tick-borne microorganisms in distinct environments and more than 80 metabolic variations in response to varying blood engorgement statuses. Interestingly, nine pathways were identified, particularly related to chorismate synthesis and carbohydrate metabolism. Moreover, microbial network relationships within tick-borne microorganism groups were highly distinct across different environments and blood-engorgement statuses. The microbial network relationships of symbionts involve some pathogenic and environmental microorganisms. Regression modelling highlighted positive correlations between the Coxiella symbiont and related pathogens, while some environmental bacteria showed strong negative correlations with Coxiella abundance. We also identified commensal bacteria/pathogens in bacterial cooccurrence patterns. Furthermore, we tested pathogenic microorganisms of each tick sample analysis revealed that 86.36% (1601/1855) of the tick samples carried one or more pathogenic microorganisms, The total carrier rate of bacterial pathogens was 43.77% ((812/1855). Most blood samples carried at least one pathogenic microorganism. The pathogens carried by the ticks have both genus and species diversity, and Rickettsia species are the most abundant pathogens among all pathogens. CONCLUSION: Our findings underscore that the bacterial pattern of ticks is dynamic and unstable, which is influenced by the environment factors and tick developmental characteristics.

A novel regulator of wheat tillering LT1 identified by using an upgraded BSA method, uni-BSA.

Branching/tillering is a critical process for plant architecture and grain yield. However, Branching is intricately controlled by both endogenous and environmental factors. The underlying mechanisms of tillering in wheat remain poorly understood. In this study, we identified Less Tiller 1 (LT1) as a novel regulator of wheat tillering using an enhanced bulked segregant analysis (BSA) method, uni-BSA. This method effectively reduces alignment noise caused by the high repetitive sequence content in the wheat genome. Loss-of-function of LT1 results in fewer tillers due to defects in axillary meristem initiation and bud outgrowth. We mapped LT1 to a 6 Mb region on the chromosome 2D short arm and validated a nucleotide-binding (NB) domain encoding gene as LT1 using CRISPR/Cas9. Furthermore, the lower sucrose concentration in the shoot bases of lt1 might result in inadequate bud outgrowth due to disturbances in the sucrose biosynthesis pathways. Co-expression analysis suggests that LT1 controls tillering by regulating TaROX/TaLAX1, the ortholog of the Arabidopsis tiller regulator REGULATOR OF AXILLARY MERISTEM FORMATION (ROX) or the rice axillary meristem regulator LAX PANICLE1 (LAX1). This study not only offers a novel genetic resource for cultivating optimal plant architecture but also underscores the importance of our innovative BSA method. This uni-BSA method enables the swift and precise identification of pivotal genes associated with significant agronomic traits, thereby hastening gene cloning and crop breeding processes in wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01484-7.

Application of DNA barcodes in the genetic diversity of hard ticks (Acari: Ixodidae) in Kazakhstan.

Forty-five tick species have been recorded in Kazakhstan. However, their genetic diversity and evolutionary relationships, particularly when compared to ticks in neighbouring countries, remain unclear. In the present study, 148 mitochondrial cytochrome c oxidase subunit I (COI) sequence data from our laboratory and NCBI (National Center for Biotechnology Information; https://www.ncbi.nlm.nih.gov/ ) data were used to address this knowledge gap. Phylogenetic analyses showed that i) Hyalomma anatolicum anatolicum (Koch, 1844) ticks from Jambyl Oblast (southeastern Kazakhstan) and Gansu Province (northwestern China) constituted a newly deviated clade; and ii) Dermacentor reticulatus (Fabricius, 1974) ticks from South Kazakhstan Oblast were closer to those in Romania and Turkey. The network diagram of haplotypes showed that i) the H-1 and H-2 haplotypes of Dermacentor marginatus (Sulzer, 1776) ticks from Zhetisu and Almaty were all newly evolved; and ii) the H-3 haplotypes of Haemaphysalis erinacei (Pavesi, 1884) from Almaty Oblast and Xinjiang Uygur Autonomous Region (northwestern China) were evolved from the H-1 haplotype from Italy. In the future, more COI data from different tick species, especially from Kazakhstan and neighbouring countries, should be employed in the field of tick DNA barcoding.

Genetic characteristics of an amikacin-resistant Brucella abortus strain first isolated from Marmota himalayana.

Brucella spp. are facultative intracellular pathogens that can persistently colonize animal host cells and cause zoonotic brucellosis. Brucellosis affects public health and safety and even affects economic development. Our lab found that a Brucella strain isolated from Marmota himalayana exhibited amikacin resistance. To annotate and analyze the potential resistance genes in this strain, we utilized sequencing platforms in this study and cloned potential resistance genes. The findings showed that the isolated strain belonged to B. abortus biovar 1 and was similar to B. abortus 2308. The isolate had amikacin resistance genes encoding aminoglycoside 3'-phosphotransferase. Based on the results of genome analysis, the isolated strain may have obtained amikacin resistance genes from Salmonella spp. through Tn3 family transposons. Notably, this study establishes a foundation for further research on the resistance mechanism of Brucella spp. and provides data that may be useful for the prevention and control of drug-resistant Brucella strains.

Koumiss promotes Mycobacterium bovis infection by disturbing intestinal flora and inhibiting endoplasmic reticulum stress.

Mycobacterium bovis is the causative agent of bovine tuberculosis and also responsible for serious threat to public health. Koumiss is a fermented mare's milk product, used as traditional drink. Here, we explored the effect of koumiss on gut microbiota and the host immune response against M bovis infection. Therefore, mice were treated with koumiss and fresh mare milk for 14 days before M bovis infection and continue for 5 weeks after infection. The results showed a clear change in the intestinal flora of mice treated with koumiss, and the lungs of mice treated with koumiss showed severe edema, inflammatory infiltration, and pulmonary nodules in M bovis-infected mice. Notably, we found that the content of short-chain fatty acids was significantly lower in the koumiss-treated group compared with the control group. However, the expression of endoplasmic reticulum stress and apoptosis-related proteins in the lungs of koumiss-treated mice were significantly decreased. Collectively, these findings suggest that koumiss treatment disturb the intestinal flora of, which is associated with disease severity and the possible mechanism that induces lungs pathology. Our current findings can be exploited further to establish the "gut-lung" axis which might be a novel strategy for the control of tuberculosis.

MicroRNA alteration in cerebrospinal fluid from comatose patients with traumatic brain injury after right median nerve stimulation.

Electrical stimulation of the right median nerve can aid coma arousal after traumatic brain injury (TBI). This study aimed to confirm the efficacy further and explore possible mechanisms of right median nerve electrical stimulation (RMNS). Five comatose patients after severe TBI from May to September 2020 in the Tianjin Medical University General Hospital received RMNS for 2 weeks besides standard management. After the 2-week treatment, the mean Glasgow Coma Scale (GCS) and neurophysiological examination were used. We then investigated the alterations in microRNA (miRNA) expression in cerebrospinal fluid (CSF) by high-throughput whole transcriptome sequencing, analyzed the data by Gene Ontology (GO) and pathway analysis, and constructed the miRNA-target gene network. Patient awareness and brain function showed a more rapid increase after treatment. We also found 38 differently expressed miRNAs, 34 of which were upregulated and 4 downregulated. GO analysis showed a relation of these differentially expressed miRNAs with neuronal growth, repair, and neural signal transmission. The most highly correlated pathways were primarily associated with the tumor necrosis factor (TNF) signaling pathway and dopaminergic synapse. The application of RMNS effectively promoted early awakening in comatose patients with severe TBI. Moreover, differentially expressed miRNAs might reduce neuronal apoptosis and increase dopamine levels by regulating target gene expression, thus participating in the specific biological process after arousal therapy. Our study provided novel targets for further research on the molecular mechanisms of RMNS arousal treatment and a new way to treat neurotraumatic diseases.

KLK12 Regulates MMP-1 and MMP-9 via Bradykinin Receptors: Biomarkers for Differentiating Latent and Active Bovine Tuberculosis.

It has been established that kallikrein12 (KLK12) expression is closely related to bovine tuberculosis (bTB) development. Herein, we sought to clarify the regulatory mechanism of KLK12 and its application in tuberculosis diagnosis. KLK12 knockdown macrophages were produced by siRNA transfection. Bradykinin receptors (BR, including B1R and B2R) were blocked with specific inhibitors. Mannose-capped lipoarabinomannan (ManLAM) was extracted from Mycobacterium bovis (M. bovis) and used to study the mechanism of KLK12 activation. In addition, we constructed different mouse models representing the latent and active stages of M. bovis infection. Mouse models and clinical serum samples were used to assess the diagnostic value of biomarkers. Through the above methods, we confirmed that KLK12 regulates MMP-1 and MMP-9 via BR. KLK12 upregulation is mediated by the M. bovis-specific antigen ManLAM. KLK12, MMP-1, and MMP-9 harbor significant value as serological markers for differentiating between latent and active bTB, especially KLK12. In conclusion, we identified a novel signaling pathway, KLK12/BR/ERK/MMPs, in M. bovis-infected macrophages, which is activated by ManLAM. From this signaling pathway, KLK12 can be used as a serological marker to differentiate between latent and active bTB. Importantly, KLK12 also has enormous potential for the clinical diagnosis of human tuberculosis (TB).

Human Tacheng Tick Virus 2 Infection, China, 2019.

We used metagenomic analysis to identify Tacheng tick virus 2 infection in a patient with a history of tick bite in northwestern China. We confirmed the virus with reverse transcription-PCR, virus isolation, and genomic analysis. We detected viral RNA in 9.6% of ticks collected from the same region.

Development of an antigen-capture enzyme-linked immunosorbent assay for diagnosis of Aleutian mink disease virus.

Aleutian mink disease (AMD), caused by Aleutian mink disease virus (AMDV), is a very important infectious disease of mink. Currently, elimination of antibody- or antigen-positive animals is the most successful strategy for eradicating AMD, but the claw-cutting method of blood sampling is difficult to perform and painful for the animal. In this study, we aimed to establish an antigen capture enzyme-linked immunosorbent assay (AC-ELISA) method for the efficient detection of AMDV antigens using fecal samples. A purified mouse monoclonal antibody (mAb) was used as the capture antibody, and a rabbit polyclonal antibody (pAb) was used as the detection antibody. The assay was optimized by adjusting a series of parameters. Using a cutoff value of 0.205, the limit of detection of the AC-ELISA for strain AMDV-G antigen was 2 µg/mL, and there was no cross-reaction with other mink viruses. The intra- and inter-assay standard deviations were below 0.046, and the correlation of variance (CV) values were 1.24-7.12% when testing fecal samples. Compared with conventional PCR results, the specificity and sensitivity were 91.5% and 90.6%, respectively, and the concordance rate between the two methods was 91.1%.

A tick bite patient with fever and meningitis co-infected with Rickettsia raoultii and Tacheng tick virus 1: a case report.

BACKGROUND: Increasing numbers of tick-borne pathogens are being discovered, including those that infect humans. However, reports on co-infections caused by two or more tick-borne pathogens are scarce. CASE PRESENTATION: A 38-year-old male farmer was bitten by a hard tick, presented with fever (37.7 °C), severe headache and ejection vomiting. Lumbar puncture was performed in the lateral decubitus. The cerebrospinal fluid (CSF) was clear, and analysis showed severe increased pressure (320 mm H2O), mild leukocytosis (126.0 × 106/L, mononuclear cells accounting for 73%) and elevated total protein concentration (0.92 g/L). Bacterial cultures of CSF and blood were negative. The diagnosis of Rickettsia raoultii and Tacheng tick virus 1 (TcTV-1) co-infection was confirmed by amplifying four rickettsial genetic markers and the partial small (S) RNA segment of TcTV-1 from the patient's blood. The patient gradually recovered after treatment with levofloxacin and ribavirin. CONCLUSIONS: This is the first reported co-infection case with fever and meningitis caused by R. raoultii and TcTV-1. It is vital to screen for multiple pathogens in tick-bitten patients, especially in those with severe complex symptoms.

A case report of endocarditis and spondylitis caused by Brucella melitensis biovar 3.

BACKGROUND: This case report describes the clinical process of a shepherd who suffered brucellosis-related endocarditis (BE) and spondylitis (BS) and was infected with Brucella melitensis biovar 3 (B. melitensis biovar 3). CASE PRESENTATION: A 55-year-old male patient was admitted to The First Affiliated Hospital of Shihezi University on October 11, 2018, due to over 3 months of intermittent fever, back pain, and heart trouble. The Rose Bengal Plate test was positive, the standard agglutination test titer for brucellosis was 1/800, and the blood culture was positive for B. melitensis biovar 3. Three instances of transthoracic echocardiography examination at days 1, 25, and 376 after admission to the hospital and magnetic resonance imaging (MRI) and computed tomography (CT) checks at days 5 and 38 revealed that the size of the vegetation on the posterior leaflet of the mitral valve increased from 0.7 × 1.4 cm to 1.2 × 1.5 cm and that the left atrium and ventricle were enlarged. The MRI and CT results showed hyperplasia of the second and third vertebra, a cold abscess formed on both sides of the psoas major muscles, and the vertebra hyperplasia became aggravated at a later time point. The patient's situation deteriorated, and heart failure was discovered on October 22, 2019. At the moment of submission of this manuscript, the patient remains in bed at home because of severe debility caused by brucellosis. CONCLUSIONS: This is the first reported case of endocarditis combined with spondylitis caused by B. melitensis biovar 3 in a shepherd. Brucellosis infection can cause work-power losses because of misdiagnosis or a lack of proper treatment. Early diagnosis and treatment are essential for a successful outcome.

Genetic Diversity of Hard Ticks (Acari: Ixodidae) in the South and East Regions of Kazakhstan and Northwestern China.

To date, there is no report on the genetic diversity of ticks in these regions. A total of 370 representative ticks from the south and east regions of Kazakhstan (SERK) and Xinjiang Uygur Autonomous Region (XUAR) were selected for molecular comparison. A fragment of the mitochondrial cytochrome c oxidase subunit I (cox1) gene, ranging from 631 bp to 889 bp, was used to analyze genetic diversity among these ticks. Phylogenetic analyses indicated 7 tick species including Hyalomma asiaticum, Hyalomma detritum, Hyalomma anatolicum, Dermacentor marginatus, Rhipicephalus sanguineus, Rhipicephalus turanicus and Haemaphysalis erinacei from the SERK clustered together with conspecific ticks from the XUAR. The network diagram of haplotypes showed that i) Hy. asiaticum from Almaty and Kyzylorda Oblasts together with that from Yuli County of XUAR constituted haplogroup H-2, and the lineage from Chimkent City of South Kazakhstan was newly evolved; and ii) the R. turanicus ticks sampled in Israel, Almaty, South Kazakhstan, Usu City, Ulugqat and Baicheng Counties of XUAR were derivated from an old lineage in Alataw City of XUAR. These findings indicate that: i) Hy. asiaticum, R. turanicus and Ha. erinacei shared genetic similarities between the SERK and XUAR; and ii) Hy. marginatum and D. reticulatus show differences in their evolution.

A Tentative Tamdy Orthonairovirus Related to Febrile Illness in Northwestern China.

BACKGROUND: Many novel tick-borne viruses have been discovered by deep-sequencing technology in recent years; however, their medical significance is unknown. METHODS: We obtained clinical data of a patient from Xinjiang, China. Possible pathogens were detected by metagenomic analysis; the causative pathogen Tacheng tick virus 1 (TcTV-1) was found and further confirmed by reverse transcriptase-polymerase chain reaction, viral culture, and sequence analyses. Epidemiological investigation was conducted in the local human population, domestic animals, and ticks by serological/molecular methods. RESULTS: A 62-year-old woman with a history of tick bite in Qinghe, Xinjiang, presented with fever and rashes. These symptoms were relieved after clinical treatment. TcTV-1 (strain QH1) was isolated from the patient's cerebrospinal fluid, throat swabs, and urine on day 47 after illness onset. Although the blood and urine showed viral RNA positive on day 73 after illness onset, the virus was only isolated from urine. Serological detection revealed a virus neutralizing antibody titer of 1:40 and 1:80 on day 47 and 73 after illness onset, respectively. No coinfection with other pathogens was detected, suggesting TcTV-1 may be the potential causative pathogen. We detected anti-TcTV-1 antibodies (immunoglobulin G: 10.1%; immunoglobulin M: 4.8%) in the local human population. The viral RNA was also found in cattle (4.9%), sheep (9.2%), and ticks, including Dermacentor marginatus (14.3%), Dermacentor silvarum (11.8%), Dermacentor nuttalli (6.7%), and Hyalomma asiaticum (4.8%). CONCLUSIONS: TcTV-1 may be associated with a febrile illness syndrome, and epidemiological data of the virus in humans and animals necessitate disease surveillance of TcTV-1 infection in China.

Brucella melitensis in Asian Badgers, Northwestern China.

We isolated Brucella melitensis biovar 3 from the spleen of an Asian badger (Meles leucurus) in Nilka County, northwestern China. Our investigation showed that this isolate had a common multilocus variable-number tandem-repeat analysis 16 genotype, similar to bacterial isolates from local aborted sheep fetuses.

Insights into irr and rirA gene regulation on the virulence of Brucella melitensis M5-90.

Iron is a fundamental element required by most organisms, including Brucella. Several researchers have suggested that the iron response regulator (irr) and rhizobial iron regulator (rirA) genes regulate iron acquisition by Brucella abortus, influencing heme synthesis by and virulence of this pathogen. However, little is known about another Brucella species, Brucella melitensis. In this research, we successfully constructed two mutants: M5-90Δirr and M5-90ΔrirA. The adhesion, invasion, and intracellular survivability of these two mutants were evaluated in RAW264.7 cells infected with 1 × 106 CFU of M5-90Δirr, M5-90ΔrirA, or M5-90. We also tested the sensitivity of cells to hydrogen peroxide and their ability to grow. In addition, the virulence of these two mutants was evaluated in BALB/c mice. The results showed that the ability of these two mutants to invade and adhere inside the murine macrophages RAW264.7 was attenuated but their ability to replicate intracellularly was strengthened, enhancing the resistance to hydrogen peroxide. The M5-90Δirr mutant showed stronger growth ability than the parental strain under iron-limiting conditions. No differences were observed in the number of bacteria in spleen between M5-90 and M5-90Δirr at 7 or 15 days postinfection. However, the number of M5-90ΔrirA in spleen reduced significantly at 15 days postinfection. The splenic index of the M5-90Δirr group is evidently lower than that of M5-90. This is the first report that irr and rirA genes of B. melitensis are associated not only with virulence but also with growth ability. Together, our data suggest that M5-90Δirr is a promising Brucella vaccine candidate.

Seeing Pedestrian in the Dark via Multi-Task Feature Fusing-Sharing Learning for Imaging Sensors.

Pedestrian detection is an essential problem of computer vision, which has achieved tremendous success under controllable conditions using visible light imaging sensors in recent years. However, most of them do not consider low-light environments which are very common in real-world applications. In this paper, we propose a novel pedestrian detection algorithm using multi-task learning to address this challenge in low-light environments. Specifically, the proposed multi-task learning method is different from the most commonly used multi-task learning method-the parameter sharing mechanism-in deep learning. We design a novel multi-task learning method with feature-level fusion and a sharing mechanism. The proposed approach contains three parts: an image relighting subnetwork, a pedestrian detection subnetwork, and a feature-level multi-task fusion learning module. The image relighting subnetwork adjusts the low-light image quality for detection, the pedestrian detection subnetwork learns enhanced features for prediction, and the feature-level multi-task fusion learning module fuses and shares features among component networks for boosting image relighting and detection performance simultaneously. Experimental results show that the proposed approach consistently and significantly improves the performance of pedestrian detection on low-light images obtained by visible light imaging sensor.

A case with neurological abnormalities caused by Rickettsia raoultii in northwestern China.

BACKGROUND: The number of new rickettsial species are rapidly increasing, and increasing numbers of Rickettsia raoultii (R. raoultii) infection cases have been detected in humans. However, neurological abnormalities caused by R. raoultii are rarely reported, especially in northwestern China. CASE PRESENTATION: A 36-year-old Kazakh shepherd with an attached tick on part temporalis, presented with right eyelid droop, lethargy, fever, headache, fever (38.0-41.0 °C) and erythematous rash. The examination of cerebrospinal fluid (CSF) showed cerebrospinal pressure of 200 mm H2O, leukocyte count of 300.0 × 106/L, adenosine deaminase of 2.15 U/L, and total protein concentration of 0.93 g/L. The diagnosis of R. raoultii infection was confirmed by six genetic markers, and semi-quantified by enzyme-linked immunosorbent assay for rickettsial antigen. The patient gradually recovered after treatment with doxycycline and ceftriaxone. R. raoultii DNA was found both in a tick detached from this patient and in 0.18% (2/1107) of blood samples collected from local shepherds. CONCLUSIONS: This is the first reported case with neurological abnormalities caused by R. raoultii in northwestern China. It is vital to detect rickettsial agents both in blood and CSF for tick bite patients with neurological abnormalities. Public health workers and physicians should pay attention to neurological abnormalities caused by Rickettsia.