Pasteurella multocida strains of a novel capsular serotype and lethal to Marmota himalayana on Qinghai-Tibet plateau in China.

Pasteurella multocida is a zoonotic pathogen causing serious diseases in humans and animals. Here, we report P. multocida from wildlife on China's Qinghai-Tibet plateau with a novel capsular serotype, forming a single branch on the core-genome phylogenetic tree: four strains isolated from dead Himalayan marmot (Marmota himalayana) and one genome assembled from metagenomic sequencing of a dead Woolly hare (Lepus oiostolus). Four of the strains were identified as subspecies multocida and one was septica. The mouse model showed that the challenge strain killed mice within 24 h at an infectious dose of less than 300 bacteria. The short disease course is comparable to septicemic plague: the host has died before more severe pathological changes could take place. Though pathological changes were relatively mild, cytokine storm was obvious with a significant rise of IL-12p70, IL-6, TNF-αand IL-10 (P < 0.05). Our findings suggested P. multocida is a lethal pathogen for wildlife on Qinghai-Tibet plateau, in addition to Yersinia pestis. Individuals residing within the M. himalayana plague focus are at risk for P. multocida infection, and public health warnings are necessitated.

A preliminary study of multispectral Cherenkov imaging and a Fricke-xylenol orange gel film (MCIFF) for online, absolute dose measurement.

BACKGROUND: Cherenkov luminescence imaging has shown potential for relative dose distribution and field verification in radiation therapy. However, to date, limited research utilizing Cherenkov luminescence for absolute dose calibration has been conducted owing to uncertainties arising from camera positioning and tissue surface optical properties. PURPOSE: This paper introduces a novel approach to multispectral Cherenkov luminescence imaging combined with Fricke-xylenol orange gel (FXG) film, termed MCIFF, which can enable online full-field absolute dose measurement. By integrating these two approaches, MCIFF allows for calibration of the ratio between two spectral intensities with absorbed dose, thereby enabling absolute dose measurement. METHODS: All experiments are conducted on a Varian Clinac 23EX, utilizing an electron multiplying charge-coupled device (EMCCD) camera and a two-way image splitter for simultaneous capture of two-spectral Cherenkov imaging. In the first part of this study, the absorbance curves of the prepared FXG film, which receives different doses, are measured using a fluorescence spectrophotometer to verify the correlation between absorbance and dose. In the second part, the FXG film is positioned directly under the radiation beam to corroborate the dose measurement capacity of MCIFF across various beams. In the third part, the feasibility of MCIFF is tested in actual radiotherapy settings via a humanoid model, demonstrating its versatility with various radiotherapy materials. RESULTS: The results of this study indicate that the logarithmic ratios of spectral intensities at wavelengths of 550 ± 50 and 700 ± 100 nm accurately reflect variations in radiation dose (R2 > 0.96) across different radiation beams, particle energies, and dose rates. The slopes of the fitting lines remain consistent under varying beam conditions, with discrepancies of less than 8%. The optical profiles obtained using the MCIFF exhibit a satisfactory level of agreement with the measured results derived from the treatment planning system (TPS) and EBT3 films. Specifically, for photon beams, the lateral distances between the 80% and 20% isodose lines, referred to as the penumbra (P80-20) values, obtained through TPS, EBT3 films, and MCIFF, are determined as 0.537, 0.664, and 0.848 cm, respectively. Similarly, for electron beams, the P80-20 values obtained through TPS, EBT3 films, and MCIFF are found to be 0.432, 0.561, and 0.634 cm, respectively. Furthermore, imaging of the anthropomorphic phantom demonstrates the practical application of MCIFF in real radiotherapy environments. CONCLUSION: By combining an FXG film with Cherenkov luminescence imaging, MCIFF can calibrate Cherenkov luminescence to absorbed dose, filling the gap in online 2D absolute dose measurement methods in clinical practice, and providing a new direction for the clinical application of optical imaging to radiation therapy.

Low radiotherapy dose is suitable for brain metastases in SCLC compared with high dose.

Objective: This study was designed to evaluate the suitable radiotherapy dose in SCLC patients with BM. Methods: A retrospective analysis was performed among 121 patients on the prognosis of BM of SCLC who were admitted to our hospital from 2013 to 2023. They all received first line chemotherapy. 80 patients of them received TRT after chemotherapy. The Chi square method was used to compare the categorical data. Univariate survival analysis was estimated by Kaplan Meier method and the logrank was used to compare survival curves between groups. A multivariate prognostic analysis was made by the Cox proportional hazard model. The iOS and iLC of two groups of low dose and high dose were analyzed after propensity score matching (PSM). Results: In all the patients, the median follow-up time was 18.6 months (range 6.30~85.7), the 2-year iOS and iLC rates were 15.4% and 70.3%, respectively, and cerebral necrosis occurred in 2 patients. In univariate analysis related to iOS, extracranial disease control (p=0.023), higher DS-GPA (≥2) (p=0.016), immunotherapy (p=0.049), low-dose(p=0.030), and WBRT+SIB (p=0.009) were significantly associated with an increase in survival rate. After PSM, the 2-year iOS of low dose (n=49) was significantly higher than that of high dose (n=49) (P=0.025), while the 2-year iLC was not significantly improved (P=0.267). In DS-GPA < 2 subgroup, the iOS of low dose group was significantly higher than that of high dose group (p=0.019). In the DS-GPA ≥ 2 subgroup, the 2-year iLC of the low dose group was significantly inferior than that of the high dose group (p=0.044). Conclusions: The iLC was improved along with increasing radiotherapy dose, but high dose had inferior iOS compared to low dose, while there were not significantly improving iLC when radiotherapy BED >56Gy. But in patients with DS-GPA≥2 subgroup, high dose brought better iLC benefits.

The complex genomic diversity of Yersinia pestis on the long-term plague foci in Qinghai-Tibet plateau.

Plague is a typical natural focus disease that circulates in different ecology of vectors and reservoir hosts. We conducted genomic population and phylogenetic analyses of the Yersinia pestis collected from the 12 natural plague foci in China with more than 20 kinds of hosts and vectors. Different ecological landscapes with specific hosts, vectors, and habitat which shape various niches for Y. pestis. The phylogeographic diversity of Y. pestis in different kinds plague foci in China showed host niches adaptation. Most natural plague foci strains are region-and focus-specific, with one predominant subpopulation; but the isolates from the Qinghai-Tibet plateau harbor a higher genetic diversity than other foci. The Y. pestis from Marmota himalayana plague foci are defined as the ancestors of different populations at the root of the evolutionary tree, suggesting several different evolutionary paths to other foci. It has the largest pan-genome and widest SNP distances with most accessory genes enriched in mobilome functions (prophages, transposons). Geological barriers play an important role in the maintenance of local Y. pestis species and block the introduction of non-native strains. This study provides new insights into the control of plague outbreaks and epidemics, deepened the understanding of the evolutionary history of MHPF (M. himalayana plague focus) in China. The population structure and identify clades among different natural foci of China renewed the space cognition of the plague.

Identification of Novel Bartonella washoensis Sequence Type 22 in Marmota himalayana - Jiuquan City, Gansu Province, China, 2021-2022.

What is already known about this topic?: The prevalence of rodent-adapted Bartonella species has been increasing significantly. However, the specific Bartonella species carried by Marmota himalayana (M. himalayana), a large rodent species, and the potential risk it poses to human populations remain unknown. What is added by this report?: Bartonella washoensis (B. washoensis), associated with human endocarditis, was initially identified in M. himalayana, exhibiting a detection rate of approximately one-third and demonstrating a predilection for the heart and lungs. The discovery of the novel Sequence Type 22 has expanded both the isolation source and genetic lineage of B. washoensis. What are the implications for public health practice?: Individuals residing within the M. himalayana plague focus are at an elevated risk for B. washoensis infection. Consequently, there is a pressing need for public health warnings and efficient clinical case identification in this population.

Case Report: Screening and Analysis for Brucellosis in Akesai Kazak Autonomous County, China.

Brucellosis is a common zoonotic disease. For this study, the residents of Akesai Kazak Autonomous County, located in the high altitude of the Altun Mountains region of Gansu Province, were selected. These people rely on traditional animal husbandry for their main income. The prevalence of brucellosis and the change of antibody titer in this high-risk population were analyzed, and information on the epidemic in animals in the county was obtained from data records. One hundred ninety-nine persons were screened and 240 serum samples were collected. Eight persons and 27 serum samples were positive based on the rose bengal plate test, and seven persons were confirmed positive by standard agglutination test; 16,000 sheep were tested, of which 130 from nine different households were serum antibody positive. The results indicate that brucellosis seroprevalence increased among sheep and high-risk populations, and the occurrence of cases corresponded to the epidemic among animals. The incidence of human brucellosis was closely related to occupation, and the cases were mainly distributed among herdsmen and butchers. Most cases were asymptomatic or mild, and the serum antibody titers showed a high initial titer but a rapid decline in young cases, whereas those in older cases were relatively low but showed a slow decline.

Alternative splicing of a carboxyl/choline esterase gene enhances the fenpropathrin tolerance of Tetranychus cinnabarinus.

Detoxification plays a crucial role in agricultural pests to withstand pesticides, and cytochrome P450s, carboxyl/choline esterases (CCEs), and glutathione-S-transferases are the main proteins responsible for their detoxification ability. The activity of CCEs can be upregulated, downregulated, or modified by mutation. However, few studies have examined the role of alternative splicing in altering the properties of CCEs. We identified 2 variants of TcCCE23 in Tetranychus cinnabarinus: a long version (CCE23-V1) and a short version that is 18 nucleotides shorter than CCE23-V1 (CCE23-V2). Whether splicing affects the activity of TcCCE23 remains unclear. Overexpression of CCE23-V2 in fenpropathrin-resistant T. cinnabarinus revealed that splicing affected the detoxification of fenpropathrin by CCE23-V2. The mortality of mites was significantly higher when the expression of CCE23-V2 was knocked down (43.2% ± 3.3%) via injection of CCE23-dsRNA (double-stranded RNA) compared with the control group injected with green fluorescent protein-dsRNA under fenpropathrin exposure; however, the downregulation of CCE23-V1 (61.3% ± 6.3%) by CCE23-small interfering RNA had no such effect, indicating CCE23-V2 plays a greater role in xenobiotic metabolism than CCE23-V1. The tolerance of flies overexpressing CCE23-V2 to fenpropathrin (50% lethal dose [LD50 ] = 19.47 µg/g) was significantly higher than that of Gal4/UAS-CCE23-V1 transgenic flies (LD50  = 13.11 µg/g). Molecular docking analysis showed that splicing opened a "gate" that enlarges the substrate binding cavity of CCE23-V2, might enhance the ability of CCE23-V2 to harbor fenpropathrin molecules. These findings suggest that splicing might enhance the detoxifying capability of TcCCE23. Generally, our data improve the understanding of the diversity and complexity of the mechanisms underlying the regulation of CCEs.

Enhanced Cherenkov imaging for real-time beam visualization by applying a novel carbon quantum dot sheeting in radiotherapy.

BACKGROUND: Cherenkov imaging can be used to visualize the placement of the beam directly on the patient's surface tissue and evaluate the accuracy of treatment planning. However, Cherenkov emission intensity is lower than ambient light. At present, time gating is the only way to realize Cherenkov imaging with ambient light. PURPOSE: This study proposes preparing a novel carbon quantum dot (cQD) sheeting to adjust the wavelength of Cherenkov emission to obtain the optimal wavelength meeting the sensitive detection region of the camera, meanwhile the total optical signal is also increased. By combining a specific filter, this approach might help in using lower-cost camera systems without intensifier-coupled to accomplish in vivo monitoring of the surface beam profile on patients with ambient light. METHODS: The cQD sheetings were prepared by spin coating and UV curing with different concentrations. All experiments were performed on the Varian VitalBeam system and optical emission was captured using an electron multiplying charge-coupled device (EMCCD) camera. To quantify the optical characteristics and certify the improvement of light intensity as well as signal-to-noise ratio (SNR) of cQD sheeting, the first part of the study was carried out on solid water with 6 and 10 MV photon beams. The second part was carried out on an anthropomorphic phantom to explore the applicability of sheeting when using different radiotherapy materials and the imaging effect of sheeting with the impact of ambient light sources. Additionally, thanks to the narrow emission spectrum of the cQD, a band-pass filter was tested to reduce the effect from environmental lights. RESULTS: The experimental results show that the optical intensity collected with sheeting has an excellent linear relationship (R2  > 0.99) with the dose for 6 and 10 MV photons. The full-width half maximum (FWHM) in x and y axis matched with the measured EBT film image, with accuracy in the range of ±1.2 and ±2.7 mm standard deviation, respectively. CQD sheeting can significantly improve the light intensity and SNR of optical images. Using 0.1 mg/ml sheeting as an example, the signal intensity is increased by 209%, and the SNR is increased by 147.71% at 6 MV photons. The imaging on the anthropomorphic phantom verified that cQD sheeting could be applied to different radiotherapy materials. The average optical intensity increased by about 69.25%, 63.72%, and 61.78%, respectively, after adding cQD sheeting to bolus, mask sample and the combination of bolus and mask. Corresponding SNR is improved by about 62.78%, 56.77%, and 68.80%, respectively. Through the sheeting, optical images with SNR > 5 can be obtained in the presence of ambient light and it can be improved through combining with a band-pass filter. When red ambient lights are on, the SNR is increased by about 98.85% after adding a specific filter. CONCLUSION: Through a combination of cQD sheeting and corresponding filter, light intensity and SNR of optical images can be increased significantly, and it shed new light on the promotion of the clinical application of optical imaging to visualize the beam in radiotherapy.

Serological investigation of plague and brucellosis infection in Marmota himalayana plague foci in the Altun Mountains on the Qinghai-Tibet Plateau.

The Altun Mountains are among the most active regions of Marmota himalayana plague foci of the Qinghai-Tibet Plateau where animal plague is prevalent, whereas only three human cases have been found since 1960. Animal husbandry is the main income for the local economy; brucellosis appears sometimes in animals and less often in humans. In this study, a retrospective investigation of plague and brucellosis seroprevalence among humans and animals was conducted to improve prevention and control measures for the two diseases. Animal and human sera were collected for routine surveillance from 2018 to 2021 and screened for plague and brucellosis. Yersinia pestis F1 antibody was preliminarily screened by the colloidal gold method at the monitoring site to identify previous infections with positive serology. Previous plague infection was found in 3.2% (14/432) of the studied human population having close contact with livestock, which indicates evidence of exposure to the Yersinia antigen (dead or live pathogenic materials) in the Altun Mountains. Seroprevalence of brucellosis was higher in camels (6.2%) and sheepdogs (1.8%) than in other livestock such as cattle and sheep, suggesting a possible transmission route from secondary host animals to humans.

Epidemiological Characteristics of Human and Animal Plague in Yunnan Province, China, 1950 to 2020.

This study analyzed the epidemiological characteristics of 3,464 human plague cases and the distribution pattern of 4,968 Yersinia pestis isolates from humans, hosts, and vector insects from 1950 to 2020 among two natural plague foci in Yunnan Province, China. These foci include the Rattus flavipectus plague focus of the Yunnan, Guangdong, and Fujian provinces and the Apodemus chevrieri-Eothenomys miletus plague focus of the highlands of northwestern Yunnan Province. The case fatality rate for plague in humans was 18.39% (637/3,464), and the total isolation rate of Y. pestis was 0.17% (4,968/2,975,288). Despite that the frequency of human cases declined rapidly, the animal plague fluctuated greatly, alternating between activity and inactivity in these foci. The tendency among human cases can be divided into 4 stages, 1950 to 1955, 1956 to 1989, 1990 to 2005, and 2006 to 2020. Bubonic plague accounted for the majority of cases in Yunnan, where pneumonic and septicemic plague rarely occurred. The natural plague foci have been in a relatively active state due to the stability of local ecology. Dense human population and frequent contact with host animals contribute to the high risk of human infection. This study systematically analyzed the epidemic pattern of human plague and the distribution characteristics of Y. pestis in the natural plague foci in Yunnan, providing a scientific basis for further development and adjustment of plague prevention and control strategies. IMPORTANCE Yunnan is the origin of the third plague pandemic. The analysis of human and animal plague characteristics of plague foci in Yunnan enlightens the prevention and control of the next plague pandemics. The plague characteristics of Yunnan show that human plague occurred when animal plague reached a certain scale, and strengthened surveillance of animal plague and reducing the density of host animals and transmission vectors contribute to the prevention and control of human plague outbreaks. The phenomenon of alternation between the resting period and active period of plague foci in Yunnan further proves the endogenous preservation mechanism of plague.

Tetracycline-induced effects on the nitrogen transformations in sediments: Roles of adsorption behavior and bacterial activity.

Nitrification and denitrification are the most important nitrogen transformation processes in the environment. Recently, due to widespread use, antibiotics have been reported to lead to environmental risks. Tetracycline (TC) is one of the most extensively used antibiotics in many areas. However, its reported effects on nitrogen transformations were conflicting in previous studies. In this study, the effects of TC on nitrogen transformations in sediment were investigated by analyzing TC transport and bacterial activity. It was found that the adsorption of TC onto the sediment was favorable and spontaneous, with adsorption capacity 54.3 mg/kg. The adsorption kinetics of TC onto the sediment and the isotherm fitted the Elvoich and Freundlich models, respectively, indicating that the adsorption was a chemisorption process, including electrostatic interactions and chemical bonding between TC and the sediment. TC showed no effect on nitrification in the sediment, but significantly inhibited the reduction of nitrate and nitrite during denitrification, consistent with observations made for the model denitrifier Paracoccus denitrificans under TC stress. Mechanistic study indicated that TC at 130 µg/g-cell inhibited 50.7% of P. denitrificans growth and 61.6% of cell viability. Meanwhile, the catalytic activities of the key denitrifying enzymes, nitrate reductase (NAR) and nitrite reductase (NIR), decreased to 29.1% and 68.0% of the control levels when the TC concentration was 130 µg/g-cell, suggesting that NAR was more sensitive to the TC than NIR, which contributed to a delay in nitrite accumulation.

Acousto-optic tunable bandpass filter based on acoustic-flexural-wave-induced fiber birefringence.

An acousto-optic tunable bandpass filter was proposed and fabricated based on acoustic-flexural-wave-induced single-mode fiber birefringence via coupling the core mode to a single-cladding vector mode. In the experiment, the resonant wavelength and insertion loss could be electrically tuned with a span of nearly 100 nm and a lowest insertion loss of -1.7 dB. The structure gains advantages of a large tuning range, fast speed, easy fabrication, low insertion loss, and zero frequency shift.

Simultaneous achievement of highly birefringent and nonlinear photonic crystal fibers with an elliptical tellurite core.

A novel photonic crystal fiber (PCF) with an elliptical tellurite core is proposed to realize high birefringence and high nonlinearity simultaneously as well as low confinement loss at the wavelength of 1.55 µm. The guiding properties, such as the birefringence, the nonlinearity, and the confinement loss, have been investigated by using the full vectorial finite element method. The results show that the birefringence and the nonlinear coefficient can be up to 7.57×10-2 and 188.39 W-1 Km-1, respectively, and the confinement loss can be only 10-9 dB/m. The proposed PCF can find potential applications in optical fiber sensing, polarization-maintaining transmission, and super-continuum generation.