BTBD9 attenuates manganese-induced oxidative stress and neurotoxicity by regulating insulin growth factor signaling pathway.

Manganese (Mn) is an essential mineral, but excess exposure can cause dopaminergic neurotoxicity. Restless legs syndrome (RLS) is a common neurological disorder, but the etiology and pathology remain largely unknown. The purpose of this study was to identify the role of Mn in the regulation of an RLS genetic risk factor BTBD9, characterize the function of BTBD9 in Mn-induced oxidative stress and dopaminergic neuronal dysfunction. We found that human subjects with high blood Mn levels were associated with decreased BTBD9 mRNA levels, when compared with subjects with low blood Mn levels. In A549 cells, Mn exposure decreased BTBD9 protein levels. In Caenorhabditis elegans, loss of hpo-9 (BTBD9 homolog) resulted in more susceptibility to Mn-induced oxidative stress and mitochondrial dysfunction, as well as decreased dopamine levels and alternations of dopaminergic neuronal morphology and behavior. Overexpression of hpo-9 in mutant animals restored these defects and the protection was eliminated by mutation of the forkhead box O (FOXO). In addition, expression of hpo-9 upregulated FOXO protein levels and decreased protein kinase B levels. These results suggest that elevated Mn exposure might be an environmental risk factor for RLS. Furthermore, BTBD9 functions to alleviate Mn-induced oxidative stress and neurotoxicity via regulation of insulin/insulin-like growth factor signaling pathway.

Malignant progression of liver cancer progenitors requires lysine acetyltransferase 7-acetylated and cytoplasm-translocated G protein GαS.

BACKGROUND AND AIMS: Hepatocarcinogenesis goes through HCC progenitor cells (HcPCs) to fully established HCC, and the mechanisms driving the development of HcPCs are still largely unknown. APPROACH AND RESULTS: Proteomic analysis in nonaggregated hepatocytes and aggregates containing HcPCs from a diethylnitrosamine-induced HCC mouse model was screened using a quantitative mass spectrometry-based approach to elucidate the dysregulated proteins in HcPCs. The heterotrimeric G stimulating protein α subunit (GαS) protein level was significantly increased in liver cancer progenitor HcPCs, which promotes their response to oncogenic and proinflammatory cytokine IL-6 and drives premalignant HcPCs to fully established HCC. Mechanistically, GαS was located at the membrane inside of hepatocytes and acetylated at K28 by acetyltransferase lysine acetyltransferase 7 (KAT7) under IL-6 in HcPCs, causing the acyl protein thioesterase 1-mediated depalmitoylation of GαS and its cytoplasmic translocation, which were determined by GαS K28A mimicking deacetylation or K28Q mimicking acetylation mutant mice and hepatic Kat7 knockout mouse. Then, cytoplasmic acetylated GαS associated with signal transducer and activator of transcription 3 (STAT3) to impede its interaction with suppressor of cytokine signaling 3, thus promoting in a feedforward manner STAT3 phosphorylation and the response to IL-6 in HcPCs. Clinically, GαS, especially K28-acetylated GαS, was determined to be increased in human hepatic premalignant dysplastic nodules and positively correlated with the enhanced STAT3 phosphorylation, which were in accordance with the data obtained in mouse models. CONCLUSIONS: Malignant progression of HcPCs requires increased K28-acetylated and cytoplasm-translocated GαS, causing enhanced response to IL-6 and driving premalignant HcPCs to fully established HCC, which provides mechanistic insight and a potential target for preventing hepatocarcinogenesis.

A phosphorylation-deubiquitination cascade regulates the BRCA2-RAD51 axis in homologous recombination.

Homologous recombination (HR) is one of the major DNA double-strand break (DSB) repair pathways in mammalian cells. Defects in HR trigger genomic instability and result in cancer predisposition. The defining step of HR is homologous strand exchange directed by the protein RAD51, which is recruited to DSBs by BRCA2. However, the regulation of the BRCA2-RAD51 axis remains unclear. Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM. UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2. Overexpression of UCHL3 renders breast cancer cells resistant to radiation and chemotherapy, while depletion of UCHL3 sensitizes cells to these treatments, suggesting a determinant role of UCHL3 in cancer therapy. Overall, we identify UCHL3 as a novel regulator of DNA repair and reveal a model in which a phosphorylation-deubiquitination cascade dynamically regulates the BRCA2-RAD51 pathway.

Gut microbiota changes in horses with Chlamydia.

BACKGROUND: Zoonotic diseases pose a significant threat to public health. Chlamydia, as an intracellular pathogen, can colonize the intestinal tract of humans and animals, changing the gut microbiota. However, only a few studies have evaluated alterations in the gut microbiota of horses infected with Chlamydia. Therefore, this study aimed to investigate gut microbiota and serum biochemical indicators in horses with Chlamydial infection (IG) and healthy horses (HG). Fecal and blood samples were collected from 16 horses (IG: 10; HG: 6) before morning feeding for the determination of gut microbiota and serum biochemical parameters. RESULTS: The results showed that total globulin (GLB), alanine aminotransferase (ALT), and creatine kinase (CK) levels were significantly increased in IG compared with HG. Notably, the gut microbial diversity increased in IG compared with HG. Furthermore, Moraxellaceae and Akkermanisa abundance decreased in IG, while Streptococcus, Treponema, Prevotella, and Paraprevotella abundances (13 genera of bacterial species) increased. Compared with HG, carbohydrate metabolism increased in IG while amino acid metabolism decreased. In addition, the abundance of 18 genera of bacteria was associated with the level of five serum biochemical indicators. CONCLUSIONS: In summary, this study elucidated the influence of Chlamydia infection in horses on the gut microbiota, unraveling consequential alterations in its composition and metabolic profile. Therefore, this study improves the understanding of Chlamydia-induced intestinal infections.

TDI-based continuous window compressed spatio-temporal imaging capable of flexible voxels post-interpretation.

To achieve high frame rates and continuous streaming simultaneously, we propose a compressed spatio-temporal imaging framework implemented by combining time-delay-integration sensors and coded exposure. Without additional optical coding elements and subsequent calibration required, this electronic-domain modulation enables a more compact and robust hardware structure, compared to the existing imaging modalities. By exploiting the intra-line charge transfer mechanism, we achieve a super-resolution in both temporal and spatial domains, thus multiplying the frame rate to millions of frames-per-second. In addition, the forward model with post-tunable coefficients, and two reconstruction strategies proposed therefrom, facilitate a flexible voxels post-interpretation. Finally, the effectiveness of the proposed framework is demonstrated by both numerical simulations and proof-of-concept experiments. With the prominent advantages of prolonged time window and flexible voxels post-interpretation, the proposed system will be suitable for imaging random, non-repetitive, or long-term events.

Omnidirectional defect mode in one-dimensional photonic crystal with a (chiral) hyperbolic metamaterial defect.

The wavelength of defect mode in all-dielectric photonic crystals (PCs) with a dielectric defect are blue-shifted as incident angle increases for both transverse electric and transverse magnetic (TM) polarized waves. The blue-shifted property of defect mode limits the design of some optical devices including omnidirectional optical filters and wide-angle polarization selectors. Here we introduce a hyperbolic metamaterial (HMM) layer as a defect into dielectric one-dimensional photonic crystals (1DPCs) to obtain an omnidirectional defect mode for TM polarized waves at near-infrared regimes. Since only one HMM layer is introduced, omnidirectional defect mode with transmittance as high as 71% can be realized. Because of the unusual angle-dependence of propagating phase in the HMM defect, the total phase for satisfying the resonance condition of defect mode can be unchanged in a wide-angle range at a fixed wavelength, which leads to the omnidirectional defect mode. Moreover, the manipulation of propagating phase can be generalized to the case of circularly polarized waves, and we obtain an omnidirectional defect mode for left-handed circularly polarized waves in 1DPCs with a chiral hyperbolic metamaterial defect. Nevertheless, the defect mode for right-handed circularly polarized waves is still blue-shifted. Such spin-selective omnidirectional defect mode can be utilized to greatly enhance circular dichroism in a wide-angle range up to 64.1°. Our structure facilitates the design of omnidirectional optical filters with a high transmittance and circular polarization selectors working in a wide-angle range.

Giant optical chirality in dielectric metasurfaces induced by toroidal dipole resonances.

Although toroidal dipole (TD) resonance is a highly localized mode with a high quality (Q) factor, in most chiral structures the TD resonance is much weaker than the electric or magnetic dipole resonances and contributes little to the chiral response. In this Letter, we theoretically propose a chiral all-dielectric TD metasurface that possesses giant optical chirality with a certain degree of incident-angle robustness induced by a strong TD resonance. Interestingly, the symmetry of the system can be broken simultaneously at oblique incidence to produce chiral quasi-bound states in the continuum. The nearly unchanged high-Q TD resonance within a certain range of incident angles can avoid the problem of a reduced image quality caused by the incident-angle sensitivity, as demonstrated by the polarization-multiplexed-field image displays. The giant chirality with a certain degree of incident-angle robustness induced by the TD mode would be useful in some applications, including high-quality optical imaging, high-performance asymmetric transmission, and sensing.

A nanopore counter for highly sensitive evaluation of DNA methylation and its application in in vitro diagnostics.

DNA methylation has been considered an essential epigenetic biomarker for diagnosing various diseases, such as cancer. A simple and sensitive way for DNA methylation level detection is necessary. Inspired by the label-free and ultra-high sensitivity of solid-state nanopores to double-stranded DNA (dsDNA), we proposed a nanopore counter for evaluating DNA methylation by integrating a dual-restriction endonuclease digestion strategy coupled with polymerase chain reaction (PCR) amplification. Simultaneous application of BstUI/HhaI endonucleases can ensure the full digestion of the unmethylated target DNA but shows no effect on the methylated ones. Therefore, only the methylated DNA remains intact and can trigger the subsequent PCR reaction, producing a large quantity of fixed-length PCR amplicons, which can be directly detected through glassy nanopores. By simply counting the event rate of the translocation signals, the concentration of methylated DNA can be determined to range from 1 aM to 0.1 nM, with the detection limit as low as 0.61 aM. Moreover, a 0.01% DNA methylation level was successfully distinguished. The strategy of using the nanopore counter for highly sensitive DNA methylation evaluation would be a low-cost but reliable alternative in the analysis of DNA methylation.

S100A11 Promotes Metastasis via AKT and ERK Signaling Pathways and Has a Diagnostic Role in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common and malignant liver tumor worldwide, although the treatment approaches for HCC continue to evolve, metastasis is the main reason for high mortality rates. S100 calcium-binding protein A11 (S100A11), an important member of the S100 family of small calcium-binding proteins, is overexpressed in various cells and regulates tumor development and metastasis. However, few studies report the role and underlying regulatory mechanisms of S100A11 in HCC development and metastasis. Herein, we discovered that S100A11 is overexpressed and associated with poor clinical outcomes in HCC cohorts, and we provided the first demonstration that S100A11 could serve as a novel diagnostic biomarker used in conjunction with AFP for HCC. Further analysis implied that S100A11 outperforms AFP in determining whether HCC patients have hematogenous metastasis or not. Using in vitro cell culture model, we demonstrated that S100A11 is overexpressed in metastatic hepatoma cells, knockdown of S100A11 decreases hepatoma cells proliferation, migration, invasion, and epithelial-mesenchymal transition process by inhibiting AKT and ERK signaling pathways. Altogether, our study provides new sights into the biological function and mechanisms underlying S100A11 in promoting metastasis of HCC and explores a novel target for HCC diagnosis and treatment.

USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM.

The human RecQ helicase BLM is involved in the DNA damage response, DNA metabolism, and genetic stability. Loss of function mutations in BLM cause the genetic instability/cancer predisposition syndrome Bloom syndrome. However, the molecular mechanism underlying the regulation of BLM in cancers remains largely elusive. Here, we demonstrate that the deubiquitinating enzyme USP37 interacts with BLM and that USP37 deubiquitinates and stabilizes BLM, thereby sustaining the DNA damage response (DDR). Mechanistically, DNA double-strand breaks (DSB) promotes ATM phosphorylation of USP37 and enhances the binding between USP37 and BLM. Moreover, knockdown of USP37 increases BLM polyubiquitination, accelerates its proteolysis, and impairs its function in DNA damage response. This leads to enhanced DNA damage and sensitizes breast cancer cells to DNA-damaging agents in both cell culture and in vivo mouse models. Collectively, our results establish a novel molecular mechanism for the USP37-BLM axis in regulating DSB repair with an important role in chemotherapy and radiotherapy response in human cancers.

Characterization of CpCaM, a protein potentially involved in the growth of Cryptosporidium parvum.

Cryptosporidium parvum is an important apicomplexan parasite causing severe diarrhea in both humans and animals. Calmodulin (CaM), a multifunctional and universal calcium-binding protein, contributes to the growth and development of apicomplexan parasites, but the role of CaM in C. parvum remains unknown. In this study, the CaM of C. parvum encoded by the cgd2_810 gene was expressed in Escherichia coli, and the biological functions of CpCaM were preliminarily investigated. The transcriptional level of the cgd2_810 gene peaked at 36 h post infection (pi), and the CpCaM protein was mainly located around the nucleus of the whole oocysts, in the middle of sporozoites and around the nucleus of merozoites. Anti-CpCaM antibody reduced the invasion of C. parvum sporozoites by 30.69%. The present study indicates that CpCaM is potentially involved in the growth of C. parvum. Results of the study expand our knowledge on the interaction between host and Cryptosporidium.

Angle-selective chiral absorption induced by diffractive coupling in metasurfaces.

Here we report that a simple chiral metasurface with twisted metallic cut-wire arrays enables highly efficient and continuously tunable chiral absorption over a broad spectral range by scanning the incidence angle over a few degrees. The angle-selective chiral absorption results from the surface plasmon resonance (SPR) excited by diffractive effects of the metasurface. The diffraction-assisted chiral metasurface provides a straightforward strategy for achieving dynamically tunable chiral devices and offers intriguing possibilities for various applications in on-chip chiral detectors/emitters, chiral spectrometers, chiral lasers, and so on.

On-chip multiple beam splitting assisted by bound states in the continuum.

Usually, on-chip beam splitting can be achieved by manipulating the in-plane iso-frequency curves (IFCs) of the structure, where the confinement of light along the out-of-plane direction is governed by total internal reflection. In this Letter, without needing a high-index dielectric background material for total internal reflection, we achieve on-chip beam splitting in a linear-crossing metamaterial (LCMM) mimicked by a two-dimensional photonic crystal (PhC) slab where the vertical confinement is enabled by a bound state in the continuum (BIC) and totally beyond the light cone. Particularly, the light propagating inside the LCMM can be flexibly controlled by the rotation angle of the rectangular silicon pillars in the PhC slab. On-chip triple beam splitting can further be designed by combining two kinds of LCMM with opposite rotation angles. Such light beam splitting beyond the light cone originates from the combined manipulation of the BIC and the spatial dispersion of LCMMs. Our work promotes the development of optical devices in integrated optics, such as on-chip focusing, switching, and (de)multiplexing.

DNA damage repair gene signature model for predicting prognosis and chemotherapy outcomes in lung squamous cell carcinoma.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is prone to metastasis and likely to develop resistance to chemotherapeutic drugs. DNA repair has been reported to be involved in the progression and chemoresistance of LUSC. However, the relationship between LUSC patient prognosis and DNA damage repair genes is still unclear. METHODS: The clinical information of LUSC patients and tumour gene expression level data were downloaded from the TCGA database. Unsupervised clustering and Cox regression were performed to obtain molecular subtypes and prognosis-related significant genes based on a list including 150 DNA damage repair genes downloaded from the GSEA database. The coefficients determined by the multivariate Cox regression analysis and the expression level of prognosis-related DNA damage repair genes were employed to calculate the risk score, which divided LUSC patients into two groups: the high-risk group and the low-risk group. Immune viability, overall survival, and anticarcinogen sensitivity analyses of the two groups of LUSC patients were performed by Kaplan-Meier analysis with the log rank test, ssGSEA and the pRRophetic package in R software. A time-dependent ROC curve was applied to compare the survival prediction ability of the risk score, which was used to construct a survival prediction model by multivariate Cox regression. The prediction model was used to build a nomogram, the discriminative ability of which was confirmed by C-index assessment, and its calibration was validated by calibration curve analysis. Differentially expressed DNA damage repair genes in LUSC patient tissues were retrieved by the Wilcoxon test and validated by qRT-PCR and IHC. RESULT: LUSC patients were separated into two clusters based on molecular subtypes, of which Cluster 2 was associated with worse overall survival. A prognostic prediction model for LUSC patients was constructed and validated, and a risk score calculated based on the expression levels of ten DNA damage repair genes was employed. The clinical utility was evaluated by drug sensitivity and immune filtration analyses. Thirteen-one genes were upregulated in LUSC patient samples, and we selected the top four genes that were validated by RT-PCR and IHC. CONCLUSION: We established a novel prognostic model based on DNA damage repair gene expression that can be used to predict therapeutic efficacy in LUSC patients.

A signal on-off strategy based on the digestion of DNA cubes assisted by the CRISPR-Cas12a system for ultrasensitive HBV detection in solid-state nanopores.

Solid-state nanopores have been proven as a powerful platform for label-free single-molecule analysis. However, due to its relatively low resolution and selectivity, developing biosensors with good translocation signals faces two significant challenges: (1) small-sized chemical or biological targets show difficulty in producing recognizable translocation signals because of their weak interaction with the nanopore and (2) protein interferents that widely exist in biological samples or buffers would considerably deteriorate the noise level of the nanopore, submerging the translocation signal. Herein, we demonstrate an effective way to overcome both the challenges. DNA cubes were used as signal transducers that can achieve an ultra-high (>50 : 1) signal-to-noise ratio (SNR) translocation signal, which is maintained even in protein interferent-rich buffers. A sensing strategy was constructed via hepatitis B virus (HBV) target-triggered cleavage of the component elements of the DNA cube with the assistance of the CRISPR-Cas12a technology, which caused a great drop in the translocation rate. The elements to cleave were optimized, and the sensor performance was tested in different protein stabilizer-rich buffers and human serum. Coupling with the polymerase chain reaction (PCR) pre-amplification technology, HBV-positive or -negative classification was achieved with the detection limit reaching 5 aM. It is worth noting that in our method, all reaction buffers were directly used without further optimization, which is of great help for the practical application of solid-state nanopores.

Silica-based mesoporous ion-imprinted fluorescent sensors for the detection of Pb2+in aqueous environments.

In this work, an environment-friendly core-shell material based on CDs@SiO2as the core and mesoporous ion-imprinted layer as the shell was reported. As a highly sensitive and accurate fluorescent sensor for the detection of Pb2+in environmental water, the composition combined ion imprinting technology with quantum dots to selectively quench the fluorescence of CDs by metal coordination in the presence of Pb2+, and the visual change of gradually weakening blue color could be observed by the naked eye for visual detection. The mesoporous structure significantly improved the detection recognition rate of CDs@SiO2@MIIPs.The molecularly imprinted sensor presented a favorable linear relationship over a Pb2+concentration range from 10 nmol l-1to 100 nmol l-1and a detection limit of 2.16 nmol l-1for Pb2+. The imprinting factor of the CDs@SiO2@MIIPs was 5.13. The sensor has a fast detection rate, is highly selective in the identification of Pb2+, and can be reused up to 10 times. The applicability of the method was evaluated by the determination of Pb2+in spiked environmental water samples with satisfactory results.

A divergent role of the SIRT1-TopBP1 axis in regulating metabolic checkpoint and DNA damage checkpoint.

DNA replication is executed only when cells have sufficient metabolic resources and undamaged DNA. Nutrient limitation and DNA damage cause a metabolic checkpoint and DNA damage checkpoint, respectively. Although SIRT1 activity is regulated by metabolic stress and DNA damage, its function in these stress-mediated checkpoints remains elusive. Here we report that the SIRT1-TopBP1 axis functions as a switch for both checkpoints. With glucose deprivation, SIRT1 is activated and deacetylates TopBP1, resulting in TopBP1-Treslin disassociation and DNA replication inhibition. Conversely, SIRT1 activity is inhibited under genotoxic stress, resulting in increased TopBP1 acetylation that is important for the TopBP1-Rad9 interaction and activation of the ATR-Chk1 pathway. Mechanistically, we showed that acetylation of TopBP1 changes the conformation of TopBP1, thereby facilitating its interaction with distinct partners in DNA replication and checkpoint activation. Taken together, our studies identify the SIRT1-TopBP1 axis as a key signaling mode in the regulation of the metabolic checkpoint and the DNA damage checkpoint.

The trend of the distribution of ectopic pregnancy sites and the clinical characteristics of caesarean scar pregnancy.

BACKGROUND: Ectopic pregnancy is a life-threatening occurrence and is an important cause of pregnancy-related mortality. We launched the study to investigate the distribution and its variation trend of the ectopic pregnancy sites and the clinical characteristics of caesarean scar pregnancy, to provide information for further clinical practice. METHODS: A total of 3915 patients were included in our study to calculate the distribution of the implantation sites of ectopic pregnancies. Then, we performed a χ2 test for trend and calculated the quantity of each type of ectopic pregnancy during 2012-2015 and 2016-2019 to analyse the variation trend. RESULTS: (1) The proportion of each site of ectopic pregnancy was as follows: tubal pregnancy (84.70%), ovarian pregnancy (1.56%), caesarean scar pregnancy (8.63%), abdominal pregnancy (0.61%), cornual pregnancy (2.68%), cervical pregnancy (0.49%), heterotopic pregnancy (0.43%). (2) Through the χ2 test for trend, the ratio of caesarean scar pregnancy to ectopic pregnancy showed an upward trend (P = 0.005). From 2012 to 2015 and 2016-2019, the ratio of caesarean scar pregnancy to ectopic pregnancy increased from 5.74 to 11.81% (P < 0.001). (3) A total of 72.78% (246/338) caesarean scar pregnancy patients had one caesarean delivery, 25.15% (85/338) had two caesarean deliveries, and 2.07% (7/338) had three caesarean deliveries. A total of 80.18% (271/338) had aborted before. The most common clinical manifestations were amenorrhea (98.52%), abdominal pain (25.74%) and vaginal bleeding (67.76%), the most common sign was uterine enlargement (46.75%). CONCLUSION: As the ratio of caesarean scar pregnancy increases, the caesarean delivery rate should be decreased to decrease the morbidity of caesarean scar pregnancy.

Ectopic pregnancy occurs when a fertilized ovum implants outside the endometrium of the uterine cavity, which is a life-threatening occurrence and is an important cause of pregnancy-related mortality. With the increase in pelvic and intrauterine operations, the distribution of ectopic sites has been changing, but the variation has been insufficiently studied. To investigate the distribution of ectopic sites and its variation trend in depth, we collected the data of 3915 ectopic pregnancy cases from the third affiliated hospital of Sun Yat-Sen University.Through χ² test for trend, the ratio of caesarean scar pregnancy to ectopic pregnancy showed an upward trend (P = 0.005). From 2012 to 2015 and 2016­2019, the ratio of caesarean scar pregnancy to ectopic pregnancy increased from 5.74 to 11.81% (P < 0.001). As the increasing of the ratio of caesarean scar pregnancy to ectopic pregnancy, the clinical characteristics of caesarean scar pregnancy was analysed.A total of 72.78% (246/338) caesarean scar pregnancy patients had one caesarean delivery, 25.15% (85/338) had two caesarean deliveries, and 2.07% (7/338) had three caesarean deliveries. A total of 80.18% (271/338) had aborted before. The most common clinical manifestations were amenorrhea (98.52%), abdominal pain (25.74%) and vaginal bleeding (67.76%), the most common sign was uterine enlargement (46.75%).As the ratio of caesarean scar pregnancy increases, the caesarean delivery rate should be decreased to decrease the morbidity of caesarean scar pregnancy.

A Spatiotemporal Calibration Algorithm for IMU-LiDAR Navigation System Based on Similarity of Motion Trajectories.

The fusion of light detection and ranging (LiDAR) and inertial measurement unit (IMU) sensing information can effectively improve the environment modeling and localization accuracy of navigation systems. To realize the spatiotemporal unification of data collected by the IMU and the LiDAR, a two-step spatiotemporal calibration method combining coarse and fine is proposed. The method mainly includes two aspects: (1) Modeling continuous-time trajectories of IMU attitude motion using B-spline basis functions; the motion of the LiDAR is estimated by using the normal distributions transform (NDT) point cloud registration algorithm, taking the Hausdorff distance between the local trajectories as the cost function and combining it with the hand-eye calibration method to solve the initial value of the spatiotemporal relationship between the two sensors' coordinate systems, and then using the measurement data of the IMU to correct the LiDAR distortion. (2) According to the IMU preintegration, and the point, line, and plane features of the lidar point cloud, the corresponding nonlinear optimization objective function is constructed. Combined with the corrected LiDAR data and the initial value of the spatiotemporal calibration of the coordinate systems, the target is optimized under the nonlinear graph optimization framework. The rationality, accuracy, and robustness of the proposed algorithm are verified by simulation analysis and actual test experiments. The results show that the accuracy of the proposed algorithm in the spatial coordinate system relationship calibration was better than 0.08° (3δ) and 5 mm (3δ), respectively, and the time deviation calibration accuracy was better than 0.1 ms and had strong environmental adaptability. This can meet the high-precision calibration requirements of multisensor spatiotemporal parameters of field robot navigation systems.

Drug Resistance (Dapsone, Rifampicin, Ofloxacin) and Resistance-Related Gene Mutation Features in Leprosy Patients: A Systematic Review and Meta-Analysis.

Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85-12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46-15.33) vs. 6.59% (3.66-9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65-9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82-18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02-5.77), 3.66% (95% CI: 2.41-4.90) and 1.28% (95% CI: 0.87-1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83-2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.