Systematic investigation of the Borrelia miyamotoi spirochetes in ticks, wildlife and domestic animal hosts in Yunnan province, Southwest China.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Zoonotic pathogens identified in rodents and shrews from four provinces, China, 2015-2022.

Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.

Impact of parenchyma-preserving surgical methods on treating patients with solid pseudopapillary neoplasms: A retrospective study with a large sample size.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that mainly affects young women. AIM: To evaluate the impact of parenchyma-preserving surgical methods (PPMs, including enucleation and central pancreatectomy) in the treatment of SPN patients. METHODS: From 2013 to 2019, patients who underwent pancreatectomy for SPNs were retrospectively reviewed. The baseline characteristics, intraoperative index, pathological outcomes, short-term complications and long-term follow-up data were compared between the PPM group and the conventional method (CM) group. RESULTS: In total, 166 patients were included in this study. Of them, 33 patients (19.9%) underwent PPM. Most of the tumors (104/166, 62.7%) were found accidentally. Comparing the parameters between groups, the hospital stay d (12.35 vs 13.5 d, P = 0.49), total expense (44213 vs 54084 yuan, P = 0.21), operation duration (135 vs 120 min, P = 0.71), and intraoperative bleeding volume (200 vs 100 mL, P = 0.49) did not differ between groups. Regarding pathological outcomes, tumor size (45 vs 32 mm, P = 0.07), Ki67 index (P = 0.53), peripheral tissue invasion (11.3% vs 9.1%, P = 0.43) and positive margin status (7.5% vs 6%, P = 0.28) also did not differ between groups. Moreover, PPM did not increase the risk of severe postoperative pancreatic fistula (3.8% vs 3.0%, P = 0.85) or tumor recurrence (3.0% vs 6.0%, P = 0.39). However, the number of patients who had exocrine insufficiency during follow-up was significantly lower in the PPM group (21.8% vs 3%, P = 0.024). CM was identified as an independent risk factor for pancreatic exocrine insufficiency (odds ratio = 8.195, 95% confident interval: 1.067-62.93). CONCLUSION: PPM for SPN appears to be feasible and safe for preserving the exocrine function of the pancreas.

[Optimization of Extraction Methods and Distribution Characteristics of Antibiotics and Metabolites in Sediments of a River Water-Groundwater Interaction Zone].

The river water-groundwater interaction zone is an important area for the enrichment, degradation, and transformation of pollutants and other biogeochemical processes. The distribution characteristics of antibiotics, as organic pollutants of wide concern, in the interaction zone is essential for understanding the migration and transformation process of pollutants in the environment. Due to the sensitive changes in the redox conditions and special composition of sediments in the interaction zone, this study established an effective pretreatment method for extracting 22 antibiotics and four sulfonamide metabolites in the interaction zone, and optimized the initial state of the samples, extraction temperature, pH value of the extraction solution and organic extraction solvent. The content of antibiotics in the sediments of the river water-groundwater interaction zone and lower reaches of the Hanjiang River was also analyzed. The results show that the best recovery of the target compounds is obtained by using pH 3 acetonitrile/Na2EDTA-Mcllvaine buffer(1:1, volume ratio) to digest and extract the unoxidized sediment samples at 40℃ three times using a microwave. A total of 11 antibiotics are detected in the sediments of the interaction zone in the lower reaches of the Hanjiang River, among which oxytetracycline and ofloxacin are the main compounds with the highest concentrations of 6.77 ng·g-1 and 5.81 ng·g-1, respectively. The vertical distribution of antibiotics in different sediment profiles is significantly different, which may be related to the lithology of sediments, physicochemical properties of antibiotics, and interaction between surface water and groundwater.

Wide Distribution and Genetic Diversity of Babesia microti in Small Mammals from Yunnan Province, Southwestern China.

BACKGROUND: Babesia, usually found in wild and domestic mammals worldwide, have recently been responsible for emerging malaria-like zoonosis in infected patients. Human B. microti infection has been identified in China, primarily in the Southwest along the Myanmar border but little direct surveillance of B. microti infection in rodents has been carried out here (Yunnan province). In this region, a diverse topographic range combined with tropical moisture sustains a high biodiversity of small mammals, which might play important role on Babesia transmission. METHODS: Small mammals were captured in 141 sample locations from 18 counties located Yunnan Province, and screened for B. microti-like parasites infection by a nested PCR to target 18S rRNA gene of Babesia, plus directly sequencing for positive samples. Univariate and multivariate forward stepwise logistic regression analysis was used to access the association between infections and some related risk factors. RESULTS: Infection with Babesia microti was confirmed in 2.4% (53/ 2204) of small mammals. Significant differences in prevalence rates of B. microti were observed based on variations in forest, agricultural, and residential landscapes. Furthermore, adult small mammals had higher prevalence rates than younger, pubertal mammals. The near full-length 18S rRNA gene revealed that there were two types of B. microti, Kobe and Otsu, which demonstrate the genetic diversity and regional distribution. CONCLUSIONS: There exists a wide distribution and genetic diversity of endemic B. microti in Southwestern China, warranting further investigations and monitoring of clinical disease in individuals presenting with Babesia like symptoms in these areas.

Methodological demonstration of laser beam pointing control for space gravitational wave detection missions.

In space laser interferometer gravitational wave (G.W.) detection missions, the stability of the laser beam pointing direction has to be kept at 10 nrad/√Hz. Otherwise, the beam pointing jitter noise will dominate the noise budget and make the detection of G.W. impossible. Disturbed by the residue non-conservative forces, the fluctuation of the laser beam pointing direction could be a few µrad/√Hz at frequencies from 0.1 mHz to 10 Hz. Therefore, the laser beam pointing control system is an essential requirement for those space G.W. detection missions. An on-ground test of such beam pointing control system is performed, where the Differential Wave-front Sensing technique is used to sense the beams pointing jitter. An active controlled steering mirror is employed to adjust the beam pointing direction to compensate the jitter. The experimental result shows that the pointing control system can be used for very large dynamic range up to 5 µrad. At the interested frequencies of space G.W. detection missions, between 1 mHz and 1 Hz, beam pointing stability of 6 nrad/√Hz is achieved.

The evaluation of phasemeter prototype performance for the space gravitational waves detection.

Heterodyne laser interferometry is considered as the most promising readout scheme for future space gravitational wave detection missions, in which the gravitational wave signals disguise as small phase variances within the heterodyne beat note. This makes the phasemeter, which extracts the phase information from the beat note, the key device to this system. In this paper, a prototype of phasemeter based on digital phase-locked loop technology is developed, and the major noise sources which may contribute to the noise spectra density are analyzed in detail. Two experiments are also carried out to evaluate the performance of the phasemeter prototype. The results show that the sensitivity is achieved 2π µrad/√Hz in the frequency range of 0.04 Hz-10 Hz. Due to the effect of thermal drift, the noise obviously increases with the frequencies down to 0.1 mHz.

Role of ß-Catenin in regulating the balance between TNF-α- and Fas-induced acute liver injury.

ß-Catenin plays many critical roles during various liver physiological and pathological processes. However, the role of ß-Catenin in acute liver failure remains unclear. Using hepatocyte specific ß-Catenin knockout mice, we found that loss of ß-Catenin in hepatocyte significantly reduced GalN/LPS-induced liver damage and hepatocyte apoptosis, but exacerbated Jo2-mediated liver injury. Mechanistically, the dual effects of ß-Catenin attributes on its function of inhibiting NF-κB signaling, which aggravates oxidative stress but decreases Fas expression under injury conditions. In conclusion, ß-Catenin plays an important role in regulating the balance between TNF-α and Fas-induced liver injury via its effect on NF-κB.

Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin II-induced cardiac diastolic dysfunction in mice.

AIM: To investigate whether apocynin, a NADPH oxidase inhibitor, produced cardioproteictive effects in Ang II-induced hypertensive mice, and to elucidate the underlying mechanisms. METHODS: C57BL/6 mice were subcutaneously infused Ang II for 4 weeks to mimic cardiac remodeling and fibrosis. Concomitantly the mice were administered apocynin (100 mg·kg(-1)·d(-1)) or/and the aldosterone receptor blocker eplerenone (200 mg·kg(-1)·d(-1)) via gavage for 4 weeks. Systolic blood pressure (SBP) and heart rate were measured, and transthoracic echocardiography was performed. For in vitro study, cardiac fibroblasts were treated with Ang II (10(-7) mol/L) in the presence of apocynin (10(-5) mol/L) or/and eplerenone (10(-5) mol/L). Immunohistochemistry and Western blotting were used to quantify the expression levels of NADPH oxidase and osteopontin (OPN) proteins in the cells. RESULTS: Both apocynin and eplerenone significantly decreased SBP, and markedly improved diastolic dysfunction in Ang II-induced hypertensive mice, accompanied with ameliorated oxidative stress and cardiac fibrosis. In the Ang II-treated cardiac fibroblasts, the expression levels of NOX4 and OPN proteins were markedly upregulated. Both Apocynin and eplerenone significantly suppressed the increased expression levels of NOX4 and OPN proteins in the Ang II-treated cells. In all the experiments, apocynin and eplerenone produced comparable effects. Co-administration of the two agents did not produce synergic effects. CONCLUSION: Apocynin produces cardioproteictive effects comparable to those of eplerenone. The beneficial effects of apocynin on myocardial oxidative stress and cardiac fibrosis might be mediated partly through a pathway involving NADPH oxidase and OPN.

Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats.

BACKGROUND & AIMS: Due to its anatomic connection, the liver is constantly exposed to gut-derived bacterial products or metabolites. Disruption of gut homeostasis is associated with many human diseases. The aim of this study was to determine the role of gut homeostasis in initiation and progression of hepatocellular carcinoma (HCC). METHODS: Disruption of intestinal homeostasis by penicillin or dextran sulfate sodium (DSS) and its restoration by probiotics were applied in a diethylnitrosamine (DEN) model of rat hepatocarcinogenesis. RESULTS: Patients with liver cirrhosis and HCC had significantly increased serum endotoxin levels. Chronic DEN treatment of rats was associated with an imbalance of subpopulations of the gut microflora including a significant suppression of Lactobacillus species, Bifidobacterium species and Enterococcus species as well as intestinal inflammation. Induction of enteric dysbacteriosis or intestinal inflammation by penicillin or DSS, respectively, significantly promoted tumor formation. Administration of probiotics dramatically mitigated enteric dysbacteriosis, ameliorated intestinal inflammation, and most importantly, decreased liver tumor growth and multiplicity. Interestingly, probiotics not only inhibited the translocation of endotoxin, which bears pathogen-associated molecular patterns (PAMPs) but also the activation of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1). As a result, the production of pro- and anti-inflammatory cytokines was skewed in favor of a reduced tumorigenic inflammation in the liver. CONCLUSIONS: The data highlights the importance of gut homeostasis in the pathogenesis of HCC. Modulation of the gut microbiota by probiotics may represent a new avenue for therapeutic intervention to treat or prevent HCC development.

OV6⁺ tumor-initiating cells contribute to tumor progression and invasion in human hepatocellular carcinoma.

BACKGROUND & AIMS: Accumulating evidence suggests the involvement of tumor-initiating cells (T-ICs) in cancer genesis, but whether liver T-ICs contribute to HCC invasion and metastasis remains unclear. METHODS: OV6(+) T-ICs were isolated from SMMC7721 and HuH7 cell lines by magnetic sorting. Characteristics of T-ICs were assessed by in vitro and mouse xenograft assays. Expression of OV6 was determined by immunostaining in specimens from 218 HCC patients, and Kaplan-Meier survival analysis was used to determine the correlation of OV6 expression with prognosis. RESULTS: OV6(+) T-ICs isolated from HCC cell lines not only possess a higher capacity to form tumor spheroids in vitro, but also had a greater potential to form tumors when implanted in non-obese diabetic/severe combined immunodeficient mice, suggesting their elevated self-renewal capacity and tumorigenicity. Moreover, OV6(+) T-ICs exhibited more invasive and metastatic potentials both in vitro and in vivo. Patients with more OV6(+) tumor cells were associated with aggressive clinicopathologic features and poor prognosis. CXCR4 is expressed at higher levels in OV6(+) cells. Recombinant stromal cell-derived factor-1 (SDF-1) treatment expanded the OV6(+) HCC T-ICs population, by sustaining the stem cell property of OV6(+) cells. The SDF-1 effect was blocked by a specific CXCR4 inhibitor, AMD3100, or transfection of siRNA targeting CXCR4. CONCLUSIONS: OV6(+) HCC cells may represent a subpopulation of T-ICs with augmented invasion and metastasis potential, which contribute to progression and metastasis of HCC. The SDF-1/CXCR4 axis also provides therapeutic targets for elimination of liver T-ICs.

Hepatitis B virus X (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated HBx transgenic mice.

UNLABELLED: Hepatitis B virus X (HBx) protein is implicated in hepatitis B virus (HBV)-associated liver carcinogenesis. However, it remains unclear whether HBx-expressing hepatic progenitor cells (HPCs) are attributed to liver tumor formation. In this study, by using HBx transgenic mice and a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury model, the relationship between HBx expression and tumorigenicity of HPCs was analyzed. Compared with control mice, an elevated number of EpCAM(+) cells with characteristics of HPCs was observed in HBx mice after 1 month and 4 months of DDC diet feeding. All HBx transgenic mice developed liver tumors characterized by histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma after 7 months of DDC feeding. Notably, EpCAM(+) HPCs isolated from premalignant HBx mice exposed to a DDC diet for 4 months formed subcutaneous mixed-lineage tumors (four out of six) in nonobese diabetic/severe-combined immunodeficient (NOD/SCID) mice, and none of the cells from wildtype (WT) induced tumor, indicating that HBx may induce malignant transformation of HPCs that contributes to tumorigenesis. We also found higher titers of circulating interleukin (IL)-6, activities of IL-6/STAT3, and Wnt/ß-catenin signaling pathways in HBx transgenic mice, suggesting HBx may induce intrinsic changes in HPCs by way of the above signaling that enables HPCs with tumorigenicity potential. Finally, clinical evidence showed that high HBx expression in human HBV-related HCC was statistically associated with expansion of EpCAM(+) or OV6(+) tumor cells and aggressive clinicopathologic features. CONCLUSION: HBx induces intrinsic cellular transformation promoting the expansion and tumorigenicity of HPCs in DDC-treated mice, which may be a possible origin for liver cancer induced by chronic hepatitis infection.

Hepatitis B virus infection: a favorable prognostic factor for intrahepatic cholangiocarcinoma after resection.

AIM: To study the prognostic factors for intrahepatic cholangiocarcinoma (ICC) and evaluate the impact of chronic hepatitis B virus (HBV) infection on survival rate of ICC patients. METHODS: A total of 155 ICC patients who underwent macroscopic curative resections (R0 and R1) were enrolled in this retrospective study and divided into group A with HBV infection and group B without HBV infection according to their chronic HBV infection, represented by positive hepatitis B surface antigen (HBsAg) in serum or in liver tissue. Clinicopathological characteristics and survival rate of the patients were evaluated. RESULTS: All patients underwent anatomical resection. Their 1- and 3-year survival rates were 60.6% and 32.1%, respectively. Multivariate analyses revealed that HBV infection, hepatolithiasis, microscopic satellite lesion, and lymphatic metastasis were the independent prognostic factors for the survival rate of ICC patients. The median disease-free survival time of the patients was 5.0 mo. The number of tumors, microscopic satellite lesion, and vascular invasion were the independent prognostic factors for the disease-free survival rate of the patients. The prognostic factors affecting the survival rate of ICC patients with HBV infection and those without HBV infection were not completely consistent. Alkaline phosphatase > 119 U/L, microscopic satellite lesion, vascular invasion, and lymphatic metastasis were the independent factors for the patients with HBV infection, while r-glutamyltransferase > 64 U/L, microscopic satellite lesion, and poor tumor differentiation were the independent factors for the patients without HBV infection. CONCLUSION: HBV infection is a valuable clinical factor for predicting tumor invasiveness and clinical outcome of ICC patients. ICC patients with HBV infection should be distinguished from those without HBV infection because they have different clinicopathological characteristics, prognostic factors and outcomes after surgical resection.

[Optical limiting response in Er3+-doped TeO2-Nb2O5-ZnO glass].

Nonlinear optical properties of Er+ doped heavy metal telluride glass were studied by picosecond laser pulses. The optical limiting response was measured by a transmission technique, and the reverse saturable absorption (RSA) by a Z-scan technique. When the incident power reached the threshold, the tranmitted power did not grow rapidly with the incident power as before, but remained almost constant. It means that the Er3+ -doped glass possesses an optical limiting effect. The experimental results show that the excited absorption is responsible for the measured RSA, resulting in optical limiting response. The measured data can be well simulated by a rate equation model to obtain the absorption cross sections of the excited state.

[Temporal coherent control in Er(3+)-doped telluride glass].

The authors achieved the temporal coherent control in an Er(3+)-doped telluride glass, one kind of disordered solids. The upconversion at 670 nm was modulated and the dephasing time was simulated as 300 fs. Moreover, the photon echo signal gave the dephasing time due to the phonon interaction. The agreement between the two data indicates that the interaction between the wavepacket and the phonon leads to the fast disappearance of wavepackets interference, which is helpful for the technique to be applied to the disordered solids.

[Photon avalanche upconversion in Er3+-doped telluride glass excited by 980 nm laser].

By laser excitation at the wavelength of 980 nm, efficient upconversion emission at 550 nm was observed in Er3+ doped telluride glass. The upconversion intensity varies nonlinearly with the excitation power with a threshold of 44 mW. The photon response time, of the order of tens of milliseconds, is much longer than the emission lifetimes. Moreover, the response time decreases with the increase in excitation power. The power dependence of the intensity and response time indicates that the green emission is generated through photon avalanche upconversion. Compared with 690 or 579 nm excitation wavelength, 980 nm is more efficient.

[Anti-stokes blue fluorescence and stark splitting of 3H4 in Pr3+:Y2SiO5 (YSO)].

In the Pr3+ -doped Y2SiO5, the population in 1D2 of Pr3+ can be transferred to 3P0 state via non-radiative energy transfer by the laser excitation in resonance with 3H4-->1D2 , and we can experimentally study the Stark splitting of 3H4 energy level via 3P0 -->3H4 anti-Stokes emission spectra. Because the anti-Stokes emission spectra can avoid the energy transfer between different crystallographic site 1D2 energy levels, the above splitting lines attribution is more accurate than the assignment via 1D2-->3H4 Stokes spectra by the laser excitation in resonance with 3H4-->1D2. In addition, the character of the anti-Stokes fluorescence decay time was observed.