Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy.

Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined with varying levels of success. Here, we describe a paradigm to control cancer growth that is based on both direct tumor killing and the triggering of protective immunity. Genetic ablation of serine protease inhibitor SerpinB9 (Sb9) results in the death of tumor cells in a granzyme B (GrB)-dependent manner. Sb9-deficient mice exhibited protective T cell-based host immunity to tumors in association with a decline in GrB-expressing immunosuppressive cells within the tumor microenvironment (TME). Maximal protection against tumor development was observed when the tumor and host were deficient in Sb9. The therapeutic utility of Sb9 inhibition was demonstrated by the control of tumor growth, resulting in increased survival times in mice. Our studies describe a molecular target that permits a combination of tumor ablation, interference within the TME, and immunotherapy in one potential modality.

Breakthrough infection elicits hypermutated IGHV3-53/3-66 public antibodies with broad and potent neutralizing activity against SARS-CoV-2 variants including the emerging EG.5 lineages.

The rapid emergence of SARS-CoV-2 variants of concern (VOCs) calls for efforts to study broadly neutralizing antibodies elicited by infection or vaccination so as to inform the development of vaccines and antibody therapeutics with broad protection. Here, we identified two convalescents of breakthrough infection with relatively high neutralizing titers against all tested viruses. Among 50 spike-specific monoclonal antibodies (mAbs) cloned from their B cells, the top 6 neutralizing mAbs (KXD01-06) belong to previously defined IGHV3-53/3-66 public antibodies. Although most antibodies in this class are dramatically escaped by VOCs, KXD01-06 all exhibit broad neutralizing capacity, particularly KXD01-03, which neutralize SARS-CoV-2 from prototype to the emerging EG.5.1 and FL.1.5.1. Deep mutational scanning reveals that KXD01-06 can be escaped by current and prospective variants with mutations on D420, Y421, L455, F456, N460, A475 and N487. Genetic and functional analysis further indicates that the extent of somatic hypermutation is critical for the breadth of KXD01-06 and other IGHV3-53/3-66 public antibodies. Overall, the prevalence of broadly neutralizing IGHV3-53/3-66 public antibodies in these two convalescents provides rationale for novel vaccines based on this class of antibodies. Meanwhile, KXD01-06 can be developed as candidates of therapeutics against SARS-CoV-2 through further affinity maturation.

The RhWRKY33a-RhPLATZ9 regulatory module delays petal senescence by suppressing rapid reactive oxygen species accumulation in rose flowers.

Redox homeostasis in plant cells is critical for maintaining normal growth and development because reactive oxygen species (ROS) can function as signaling molecules or toxic compounds. However, how plants fine-tune redox homeostasis during natural or stress-induced senescence remains unclear. Cut roses (Rosa hybrida), an economically important ornamental product worldwide, often undergo stress-induced precocious senescence at the post-harvest bud stage. Here, we identified RhPLATZ9, an age- and dehydration-induced PLATZ (plant AT-rich sequence and zinc-binding) protein, and determined that it functions as a transcriptional repressor in rose flowers during senescence. We also showed that RhWRKY33a regulates RhPLATZ9 expression during flower senescence. RhPLATZ9-silenced flowers and RhWRKY33a-silenced flowers showed accelerated senescence, with higher ROS contents than the control. By contrast, overexpression of RhWRKY33a or RhPLATZ9 delayed flower senescence, and overexpression in rose calli showed lower ROS accumulation than the control. RNA-sequencing analysis revealed that apoplastic NADPH oxidase genes (RhRbohs) were enriched among the upregulated differentially expressed genes in RhPLATZ9-silenced flowers compared to wild-type flowers. Yeast one-hybrid assays, electrophoretic mobility shift assays, dual luciferase assays and chromatin immunoprecipitation quantitative PCR confirmed that the RhRbohD gene is a direct target of RhPLATZ9. These findings suggest that the RhWRKY33a-RhPLATZ9-RhRbohD regulatory module acts as a brake to help maintain ROS homeostasis in petals and thus antagonize age- and stress-induced precocious senescence in rose flowers.

Effect of different antibacterial agents doping in PET-based electrospun nanofibrous membranes on air filtration and antibacterial performance.

In order to reduce the particulate matter pollution to human health in producing environments, series of polyethylene terephthalate/polyvinyl alcohol (PET/PVA) based nanofibrous membranes were fabricated and investigated the dust collection and antibacterial activity. Silver nanoparticles (AgNPs), berberine (Ber) and titanium oxide nanoparticles (TiO2NPs) were selected as antibacterial agents. These novel membranes were well-characterized using SEM, FTIR, TG, etc. techniques. Results of the dust filtration showed that PET/PVA/Ag membrane had the best filtration efficiency of 99.87% for sodium chloride (NaCl) and 99.89% for dioctyl sebacate (DEHS), held low pressure drop of 160.1 Pa for NaCl and 165.3 Pa for DEHS, and posed a high tensile strength of 4.91 MPa. The bacteriostasis studies exhibited that PET/PVA/TiO2 and PET/PVA/Ag membrane showed the highest bacteriological effect on Escherichia coli (98.7%) and Staphylococcus aureus (95.9%), respectively. Meanwhile, in vitro cytotoxicity test indicated no potential cytotoxicity existed in the cell culture process of these two antibacterial membranes. Moreover, the charge distribution in the nanofibers was increased by these antibacterial agents to improve the filtration performance. The dust filtration process synergistically promoted with the antibacterial process in the antibacterial membranes. It was expected that these membranes could be efficient filter medias with broad application prospects in the field of individual protection.

Construction and signal analysis of a reflective single-beam spin-exchange relaxation-free comagnetometer for rotation measurement.

The single-beam comagnetometer working in the spin-exchange relaxation-free (SERF) state is being developed into a miniaturized atomic sensor with extremely high precision in rotation measurement. In this paper, we propose a reflective configuration for the single-beam SERF comagnetometer. The laser light simultaneously used for optical pumping and signal extraction is designed to pass through the atomic ensemble twice. In the optical system, we propose a structure composed of a polarizing beam splitter and a quarter-wave plate. With this, the reflected light beam can be separated entirely from the forward propagating one and realize a complete light collection with a photodiode, making the least light power loss. In our reflective scheme, the length of interaction between light and atoms is extended, and because the power of the DC light component is attenuated, the photodiode can work in a more sensitive range and has a better photoelectric conversion coefficient. Compared with the single-pass scheme, our reflective configuration has a stronger output signal and performs better signal-to-noise ratio and rotation sensitivity. Our work has an important impact on developing miniaturized atomic sensors for rotation measurement in the future.

Single-beam NMOR atomic magnetometer based on a fiberized EOM.

The high-precision and portable nonlinear magneto-optical rotation (NMOR) atomic magnetometer has significant potential in the direction of magnetic field measurement under a geomagnetic environment. Here, we propose a single-beam NMOR atomic magnetometer with amplitude modulation based on a fiberized electro-optic modulator (EOM) for the first time, to the best of our knowledge, which provides a feasible scheme for the integrated design. A theoretical model of the system response signal as a function of the modulation amplitude is established by a Jones matrix. Based on the theoretical model, the influence mechanism of the modulation amplitude on the system response signal is further analyzed and the optimal modulation parameters can be determined. Finally, a sensitivity of 42.67 fT/Hz1/2 at 50-µT magnetic field is achieved. The proposed scheme is also applicable to other magnetometers under a geomagnetic environment.

PET/CT Fluoroscopy during PET/CT-Guided Interventions: Initial Experience.

This study assessed the feasibility and functionality of the use of a high-speed image fusion technology to generate and display positron emission tomography (PET)/computed tomography (CT) fluoroscopic images during PET/CT-guided tumor ablation procedures. Thirteen patients underwent 14 PET/CT-guided ablations for the treatment of 20 tumors. A Food and Drug Administration-cleared multimodal image fusion platform received images pushed from a scanner, followed by near-real-time, nonrigid image registration. The most recent intraprocedural PET dataset was fused to each single-rotation CT fluoroscopy dataset as it arrived, and the fused images were displayed on an in-room monitor. PET/CT fluoroscopic images were generated and displayed in all procedures and enabled more confident targeting in 3 procedures. The mean lag time from CT fluoroscopic image acquisition to the in-room display of the fused PET/CT fluoroscopic image was 21 seconds ± 8. The registration accuracy was visually satisfactory in 13 of 14 procedures. In conclusion, PET/CT fluoroscopy was feasible and may have the potential to facilitate PET/CT-guided procedures.

Tunable surface magnetism by gate voltage in a slab of nonmagnetic half-Heusler compound CoTiSb.

The electrical manipulation of magnetization is appealing to the relevant experiment and spintronic device. In this paper, we focus on the electrical and magnetic properties of a thin film cleaved from the nonmagnetic half-Heusler compound CoTiSb. By means of the first-principles calculations, we find that the surface of TiSb termination possesses ferrimagnetism with a magnetic moment of 0.35 (0.49) µB per unit cell without (with) Hubbard U, which can persist below the Curie temperature of 48 (54) K. What is more, such a surface magnetism can be tuned to nonmagnetism by gate-induced hole doping with a concentration of 2.83 × 1014 (3.55 × 1014) cm-2. This magnetic tunability of the CoTiSb slab provides a platform to realize the pseudo-spin valve with both the magnetic electrodes and nonmagnetic space layer made of the same material without hetero-interfaces.

Azadirachtin exposure inhibit ovary development of Spodoptera litura (Lepidoptera: Noctuidae) by altering lipids metabolism event and inhibiting insulin signaling pathways.

Lipids are main energy source for insects reproduction, which are becoming emerging target for pest management. Azadirachtin (AZA) is a multi-targeted and promising botanical insecticide, but its reproduction toxicity mechanism related to lipids metabolism is poorly understood. Here, we applied lipidomic and transcriptomic to provide a comprehensive resource for describing the effect of AZA on lipids remodeling in ovary of Spodoptera litura. The results showed that AZA exposure obviously altered the contents of 130 lipids subclasses (76 upregulated and 54 downregulated). In detail, AZA exposure changed the length and saturation degrees of fatty acyl chain of most glycerolipid, phospholipid and sphingolipid as well as the expression of genes related to biosynthesis of unsaturated fatty acids and fatty acids elongation. Besides, following the abnormal lipids metabolism, western blot analysis suggested that AZA induce insulin resistance-like phenotypes by inhibiting insulin receptor substrates (IRS) /PI3K/AKT pathway, which might be responsible for the ovary abnormalities of S. litura. Collectively, our study provided insights into the lipids metabolism event in S. litura underlying AZA exposure, these key metabolites and genes identified in this study would also provide important reference for pest control in future.

Haplotype Analysis of GmSGF14 Gene Family Reveals Its Roles in Photoperiodic Flowering and Regional Adaptation of Soybean.

Flowering time and photoperiod sensitivity are fundamental traits that determine soybean adaptation to a given region or a wide range of geographic environments. The General Regulatory Factors (GRFs), also known as 14-3-3 family, are involved in protein-protein interactions in a phosphorylation-dependent manner, thus regulating ubiquitous biological processes, such as photoperiodic flowering, plant immunity and stress response. In this study, 20 soybean GmSGF14 genes were identified and divided into two categories according to phylogenetic relationships and structural characteristics. Real-time quantitative PCR analysis revealed that GmSGF14g, GmSGF14i, GmSGF14j, GmSGF14k, GmSGF14m and GmSGF14s were highly expressed in all tissues compared to other GmSGF14 genes. In addition, we found that the transcript levels of GmSGF14 family genes in leaves varied significantly under different photoperiodic conditions, indicating that their expression responds to photoperiod. To explore the role of GmSGF14 in the regulation of soybean flowering, the geographical distribution of major haplotypes and their association with flowering time in six environments among 207 soybean germplasms were studied. Haplotype analysis confirmed that the GmSGF14mH4 harboring a frameshift mutation in the 14-3-3 domain was associated with later flowering. Geographical distribution analysis demonstrated that the haplotypes related to early flowering were frequently found in high-latitude regions, while the haplotypes associated with late flowering were mostly distributed in low-latitude regions of China. Taken together, our results reveal that the GmSGF14 family genes play essential roles in photoperiodic flowering and geographical adaptation of soybean, providing theoretical support for further exploring the function of specific genes in this family and varietal improvement for wide adaptability.

Investigation on the pulse response of a spin-exchange relaxation-free comagnetometer.

We investigate the magnetic pulse response of the optically pumped comagnetometer operated in the spin-exchange relaxation-free (SERF) regime. The pulse response model describing the evolution of the coupled spin ensemble of alkali metal and noble gas during and after the pulse is established for the first time. A three-beam comagnetometer is created with a circularly and two linearly polarized lasers to detect the responses in the three axes of the comagnetometer simultaneously and independently. The results indicate that the response to the small pulse excitation is dominated by the electron spins, while the response to the large pulse excitation and both responses after the pulse excitation consist of a fast and a slow oscillation, which are dominated by the electron spins and nuclear spins, respectively. We also observe novel dynamics of the coupled spin ensemble when the nuclear spins are tipped far away from equilibrium. The theory and method presented here can not only facilitate the investigation on the dynamics of the optically pumped coupled spin ensemble, but also shed light on the application of the pulse modulation technology in the SERF comagnetometer.

Single-beam comagnetometer using elliptically polarized light for dual-axis rotation measurement.

We have developed a single-beam spin-exchange relaxation-free comagnetometer using elliptically polarized light for dual-axis rotation measurement. The light beam propagating through the glass cell is simultaneously used for optical pumping and signal extraction. Combined with transverse magnetic field modulation, the rotation information can be collected through a balanced polarimeter module and a lock-in amplifier. Also, we propose a decoupling method by adjusting the phase shift of the reference signal, allowing the device to realize biaxial signal decoupling while still maintaining its self-compensation state. Compared to those without decoupling, our method improves the performance of our device in its signal-to-noise ratio and rotation sensitivity. The single-beam comagnetometer scheme and the decoupling method have a positive impact on the development of miniaturized atomic sensors for high-precision inertial measurement.

Positron Emission Tomography and Computed Tomography Contributions to Patient Dose and Personnel Exposure to Radiation during PET/CT-Guided Tumor Ablations.

This study sought to quantify the positron emission tomography (PET) and computed tomography (CT) components of patient radiation doses and personnel exposure to radiations during PET/CT-guided tumor ablations and assess the utility of a rolling lead shield for operator protection. Two operators performed 21 PET/CT-guided ablations behind a customized, 25-mm-thick lead shield with midchest-to-midthigh coverage. The mean patient radiation dose per procedure was 3.90 mSv ± 1.13 (11.3%) from PET and 30.51 mSv ± 19.05 (88.7%) from CT. The mean primary and secondary operator exposure outside neck-level thyroid shields was 0.05 and 0.02 mSv per procedure, respectively. The radiation exposure levels behind the rolling lead shield, inside the primary operator's thyroid shield, and on the other personnel were below the measurable threshold cumulatively over 21 procedures. The mean PET exposure level at continuous close proximity to patients was 0.02 mSv per procedure. The PET radiation doses to the patients and personnel were small. Thus, the rolling lead shield provided limited benefit.

The Role of the P1 Latency in Auditory and Speech Performance Evaluation in Cochlear Implanted Children.

Auditory deprivation affects normal age-related changes in the central auditory maturation. Cochlear implants (CIs) have already become the best treatment strategy for severe to profound hearing impairment. However, it is still hard to evaluate the speech-language outcomes of the pediatric CI recipients because of hearing-impaired children with limited speech-language abilities. The cortical auditory evoked potential (CAEP) provides a window into the development of the auditory cortical pathways. This preliminary study is aimed at assessing electrophysical characteristics of P1-N1 of electrically CAEP in children with CIs and at exploring whether these changes could be accounted for in auditory and speech outcomes of these patients. CAEP responses were recorded in 48 children with CIs in response to electrical stimulus to determine the presence of the P1-N1 response. Speech perception and speech intelligibility of the implanted children were further evaluated with the categories of auditory performance (CAP) test and speech intelligibility rating (SIR) test, respectively, to explore the relationship between the latency of P1-N1 and auditory and speech performance. This study found that P1 and N1 of the intracochlear CAEP were reliably evoked in children fitted with CIs and that the latency of the P1 as opposed to that of N1 was negative in relation to the wearing time of the cochlear implant. Moreover, the latency of the P1 produced significantly negative scores in both CAP and SIR tests, which indicates that P1 latency may be reflective of the auditory performance and speech intelligibility of pediatric CI recipients. These results suggest that the latency of P1 could be used for the objective assessment of auditory and speech function evaluation in cochlear-implanted children, which would be helpful in clinical decision-making regarding intervention for young hearing-impaired children.

Risk factors and characteristics of ischemic stroke in patients with immune thrombocytopenia: A retrospective cohort study.

OBJECTIVES: Previous research has found that patients with immune thrombocytopenia (ITP) have an increased risk of thrombosis, such as venous thromboembolism (VT), ischemic stroke (IS)/transient ischemic attack (TIA), and cardiovascular disease (CVD), but the risk factors for stroke in patients with ITP have yet to be determined. This study aims to determine the risk factors and characteristics of ischemic stroke in patients with ITP. MATERIALS AND METHODS: This study included adults with incident primary ITP diagnosed in a tertiary medical center between 2010 and 2020. The t-test and Mann-Whitney U test were used to compare the variables between IS and non-IS groups, and the multivariate logistic regression model was employed to evaluate correlations. RESULTS: The study enrolled 1824 individuals, of whom 17 (0.93%) had IS, and 138 (1:8) were randomly chosen from 1807 non-IS patients. Age was found to be substantially associated with stroke in the multivariate analysis (OR 1.07, 95% CI: 1.026-1.116; p = 0.001). We found no correlation between platelet counts (PLT) (OR 1.013, 95% CI: 0.995-1.033; p = 0.164), mean platelet volume (MPV), platelet larger cell ratio (P-LCR), prothrombin time (PT) (OR 1.455, 95% CI 0.979-2.164; p = 0.064), activated partial thromboplastin time (APTT), D-dimer, fibrinogen or antinuclear antibody (ANA) and stroke. Of 17 ITP-IS patients, 7 (53.8%) were cryptogenic, greater than the general IS population. Three (23.1%) of them had an embolic pattern. CONCLUSION: For ITP patients, age was a significant predictor of stroke. ITP-IS patients had a more cryptogenic origin, with some showing an embolic pattern.

Dynamic of land use, landscape, and their impact on ecological quality in the northern sand-prevention belt of China.

Changes in land use and landscapes have a direct impact on the regional eco-environment. It is of great importance to understand the change pattern of land use, landscapes, and their mechanism on the ecological quality, especially ecologically fragile areas. The northern sand-prevention belt (NSPB) is an important ecologically fragile area in China, which has a large influence on the ecological security of the entire country. Based on the land use data of the NSPB in 2000, 2010, and 2018, we studied the spatio-temporal characteristics of land-use change and change in landscape patterns. The ecological quality represented by the remote sensing-based desertification index (RSDI) was calculated using satellite images. The effects of land use and landscape patterns on RSDI were analyzed by geographic detector and geographically weighted regression. Important results include the following: (1) Land-use change in the study area was high during 2000-2010 but slower in 2010-2018. Grassland was the largest land-use type in the NSPB, and varied greatly in terms of total change and spatial location. The major change was the conversion between dense and moderate grass, with 64,860 km2 of dense grass turning into moderate grass, and 48,505 km2 changing the other way. (2) Among the four landscape metrics, patch density, area-weighted mean fractal dimension, and edge density increased, whereas the aggregation index decreased, which indicated that the landscape was developing towards heterogeneity, fragmentation, complexity, and aggregation. Spatially, the landscape metrics presented a strip distribution in the east of the NSPB. (3) The effects of various land-use types on ecological quality, from high to low, were unused land, woodland, dense grass, cropland, moderate grass, built-up land, sparse grass, and waterbody. The areas where the ecological quality was greatly affected by the landscape patterns were concentrated in the agro-pastoral ecotone and the forest-steppe ecotone. The results of this study reveal the trends of land use and landscape patterns in the NSPB over 18 years and can help to understand their mechanism on ecological quality, which is of significance for the management of this area.

Nuclear magnetic field measurement of the spin-exchange optically pumped noble gas in a self-compensated atomic comagnetometer.

We demonstrate a new method to determine the nuclear magnetic field of the spin-exchange optically pumped noble gas in a self-compensated atomic comagnetometer based on the steady-state AC response. The result shows that it has higher resolution and precision than a previous method based on the transient process. Furthermore, a convergence frequency is observed in the low-frequency region and its parameter dependence is studied simulatively, which may inspire further research into its relationship with the strong suppression mechanism of the self-compensation ability for the low-frequency magnetic field. We also prove that this method can be developed for suppression of residual main magnetic field to improve the systematic stability of the comagnetometer.

Radiology, Mobile Devices, and Internet of Things (IoT).

Radiology by its nature is intricately connected to the Internet and is at the forefront of technology in medicine. The past few years have seen a dramatic rise in Internet-based technology in healthcare, with imaging as a core application. Numerous Internet-based applications and technologies have made forays into medicine, and for radiology it is more seamless than in other clinical specialties. Many applications in the practice of radiology are Internet based and more applications are being added every day. Introduction of mobile devices and their integration into imaging workflow has reinforced the role played by the Internet in radiology. Due to the rapid proliferation of wearable devices and smartphones, IoT-enabled technology is evolving healthcare from conventional hub-based systems to more personalized healthcare systems. This article briefly discusses how the IoT plays a useful role in daily imaging workflow and current and potential future applications, how mobile devices can be integrated into radiology workflows, and the impact of the IoT on resident and medical student education, research, and patient engagement in radiology.

Urine podoplanin heralds the onset of ischemia-reperfusion injury of the kidney.

Ischemia-reperfusion injury represents one of the most common causes of acute kidney injury, a serious and often deadly condition that affects up to 20% of all hospitalized patients in the United States. However, the current standard assay used universally for the diagnosis of acute kidney injury, serum creatinine, does not detect renal damage early in its course. Serendipitously, we found that the immunofluorescent signal of the constitutive podocyte marker podoplanin fades in the glomerulus and intensifies in the tubulointerstitial compartment of the kidney shortly after ischemia-reperfusion injury in 8- to 10-wk-old male C57Bl/6j mice. Therefore, we sought to define the appearance and course of the podoplanin-positive signal in the kidney after ischemia-reperfusion injury. The tubulointerstitial podoplanin-positive signal increased as early as 2 h but persisted for 7 days after ischemia-reperfusion injury. In addition, the strength of this tubulointerstitial signal was directly proportional to the severity of ischemia, and its location shifted from the tubules to interstitial cells over time. Finally, we detected podoplanin in the urine of mice after ischemia, and we observed that an increase in the urine podoplanin-to-creatinine ratio correlated strongly with the onset of renal ischemia-reperfusion injury. Our findings indicate that the measurement of urine podoplanin harbors promising potential for use as a novel biomarker for the early detection of ischemia-reperfusion injury of the kidney.

Activation of fibroblastic reticular cells in kidney lymph node during crescentic glomerulonephritis.

Crescentic glomerulonephritis is an inflammatory condition characterized by rapid deterioration of kidney function. Previous studies of crescentic glomerulonephritis have focused on immune activation in the kidney. However, the role of fibroblastic reticular cells, which reside in the stromal compartment of the kidney lymph node, has not been studied in this condition. We investigated the activation of kidney lymph node-resident fibroblastic reticular cells in nephrotoxic serum nephritis, a classic murine model of crescentic glomerulonephritis. We found that increased deposition of extracellular matrix fibers by fibroblastic reticular cells in the kidney lymph node was associated with the propagation of high endothelial venules, specialized blood vessels through which lymphocytes enter the lymph node, as well as with expansion of the lymphatic vasculature. The kidney lymph node also contained an expanding population of pro-inflammatory T cells. Removal of the kidney lymph node, depletion of fibroblastic reticular cells, and treatment with anti-podoplanin antibody each resulted in reduction of kidney injury. Our findings suggest that modulating the activity of fibroblastic reticular cells may be a novel therapeutic approach in crescentic glomerulonephritis.