Attractant and repellent induce opposing changes in the four-helix bundle ligand-binding domain of a bacterial chemoreceptor.

Motile bacteria navigate toward favorable conditions and away from unfavorable environments using chemotaxis. Mechanisms of sensing attractants are well understood; however, molecular aspects of how bacteria sense repellents have not been established. Here, we identified malate as a repellent recognized by the MCP2201 chemoreceptor in a bacterium Comamonas testosteroni and showed that it binds to the same site as an attractant citrate. Binding determinants for a repellent and an attractant had only minor differences, and a single amino acid substitution in the binding site inverted the response to malate from a repellent to an attractant. We found that malate and citrate affect the oligomerization state of the ligand-binding domain in opposing way. We also observed opposing effects of repellent and attractant binding on the orientation of an alpha helix connecting the sensory domain to the transmembrane helix. We propose a model to illustrate how positive and negative signals might be generated.

Searching for Two-Neutrino and Neutrinoless Double Beta Decay of

^{134}Xe is a candidate isotope for neutrinoless double beta decay (0νßß) search. In addition, the two-neutrino case (2νßß) allowed by the standard model of particle physics has not yet been observed. With the 656-kg natural xenon in the fiducial volume of the PandaX-4T detector, which contains 10.4% of ^{134}Xe, and its initial 94.9-day exposure, we have established the most stringent constraints on 2νßß and 0νßß of ^{134}Xe half-lives, with limits of 2.8×10^{22} yr and 3.0×10^{23} yr at 90% confidence level, respectively. The 2νßß (0νßß) limit surpasses the previously reported best result by a factor of 32 (2.7), highlighting the potential of large monolithic natural xenon detectors for double beta decay searches.

Adult head and neck rhabdomyosarcoma: radiotherapy- based treatment, outcomes, and predictors of survival.

BACKGROUND: Adult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS. METHODS: We retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan-Meier method. The chi-square and Fisher's exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan-Meier method. Prognostic variables were assessed through univariate Cox analyses. RESULTS: The median patient age was 28 years (range, 16-82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis (n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival. CONCLUSIONS: The main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.

Machine learning in prenatal MRI predicts postnatal ventricular abnormalities in fetuses with isolated ventriculomegaly.

OBJECTIVES: To evaluate the intracranial structures and brain parenchyma radiomics surrounding the occipital horn of the lateral ventricle in normal fetuses (NFs) and fetuses with ventriculomegaly (FVs), as well as to predict postnatally enlarged lateral ventricle alterations in FVs. METHODS: Between January 2014 and August 2023, 141 NFs and 101 FVs underwent 1.5 T balanced steady-state free precession (BSSFP), including 68 FVs with resolved lateral ventricles (FVM-resolved) and 33 FVs with stable lateral ventricles (FVM-stable). Demographic data and intracranial structures were analyzed. To predict the enlarged ventricle alterations of FVs postnatally, logistic regression models with 5-fold cross-validation were developed based on lateral ventricle morphology, blended-cortical or/and subcortical radiomics characteristics. Validation of the models' performance was conducted using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: Significant alterations in cerebral structures were observed between NFs and FVs (p < 0.05), excluding the maximum frontal horn diameter (FD). However, there was no notable distinction between the FVM-resolved and FVM-stable groups (all p > 0.05). Based on subcortical-radiomics on the aberrant sides of FVs, this approach exhibited high efficacy in distinguishing NFs from FVs in the training/validation set, yielding an impressive AUC of 1/0.992. With an AUC value of 0.822/0.743 in the training/validation set, the Subcortical-radiomics model demonstrated its ability to predict lateral ventricle alterations in FVs, which had the greatest predictive advantages indicated by DCA. CONCLUSIONS: Microstructural alterations in subcortical parenchyma associated with ventriculomegaly can serve as predictive indicators for postnatal lateral ventricle variations in FVs. CLINICAL RELEVANCE STATEMENT: It is critical to gain pertinent information from a solitary fetal MRI to anticipate postnatal lateral ventricle alterations in fetuses with ventriculomegaly. This approach holds the potential to diminish the necessity for recurrent prenatal ultrasound or MRI examinations. KEY POINTS: Fetal ventriculomegaly is a dynamic condition that affects postnatal neurodevelopment. Machine learning and subcortical-radiomics can predict postnatal alterations in the lateral ventricle. Machine learning, applied to single-fetal MRI, might reduce required antenatal testing.

OsPDCD5 negatively regulates plant architecture and grain yield in rice.

Plant architecture is an important agronomic trait that affects crop yield. Here, we report that a gene involved in programmed cell death, OsPDCD5, negatively regulates plant architecture and grain yield in rice. We used the CRISPR/Cas9 system to introduce loss-of-function mutations into OsPDCD5 in 11 rice cultivars. Targeted mutagenesis of OsPDCD5 enhanced grain yield and improved plant architecture by increasing plant height and optimizing panicle type and grain shape. Transcriptome analysis showed that OsPDCD5 knockout affected auxin biosynthesis, as well as the gibberellin and cytokinin biosynthesis and signaling pathways. OsPDCD5 interacted directly with OsAGAP, and OsAGAP positively regulated plant architecture and grain yield in rice. Collectively, these findings demonstrate that OsPDCD5 is a promising candidate gene for breeding super rice cultivars with increased yield potential and superior quality.

A novel derivative synchronous fluorescence method for the rapid, non-destructive and intuitive differentiation of denitrifying bacteria.

It is challenging to differentiate bacteria residing in the same habitat by direct observation. This difficulty impedes the harvest, application and manipulation of functional bacteria in environmental engineering. In this study, we developed a novel method for rapid differentiation of living denitrifying bacteria based on derivative synchronous fluorescence spectroscopy, as exemplified by three heterotrophic nitrification-aerobic denitrification bacteria having the maximum nitrogen removal efficiencies greater than 90%. The intact bacteria and their living surroundings can be analyzed as an integrated target, which eliminates the need for the complex pre-processing of samples. Under the optimal synchronous scanning parameter (Δλ = 40 nm), each bacterium possesses a unique fluorescence spectral structure and the derivative synchronous fluorescence technique can significantly improve the spectral resolution compared to other conventional fluorescence methods, which enables the rapid differentiation of different bacteria through derivative synchronous fluorescence spectra as fast as 2 min per spectrum. Additionally, the derivative synchronous fluorescence technique can extract the spectral signals contributed by bacterial extracellular substances produced in the biological nitrogen removal process. Moreover, the results obtained from our method can reflect the real-time denitrification properties of bacteria in the biological nitrogen removal process of wastewater. All these merits highlight derivative synchronous fluorescence spectroscopy as a promising analytic method in the environmental field.

Search for Light Dark Matter with Ionization Signals in the PandaX-4T Experiment.

We report the search results of light dark matter through its interactions with shell electrons and nuclei, using the commissioning data from the PandaX-4T liquid xenon detector. Low energy events are selected to have an ionization-only signal between 60 to 200 photoelectrons, corresponding to a mean nuclear recoil energy from 0.77 to 2.54 keV and electronic recoil energy from 0.07 to 0.23 keV. With an effective exposure of 0.55 tonne·year, we set the most stringent limits within a mass range from 40 MeV/c^{2} to 10 GeV/c^{2} for pointlike dark matter-electron interaction, 100 MeV/c^{2} to 10 GeV/c^{2} for dark matter-electron interaction via a light mediator, and 3.2 to 4 GeV/c^{2} for dark matter-nucleon spin-independent interaction. For DM interaction with electrons, our limits are closing in on the parameter space predicted by the freeze-in and freeze-out mechanisms in the early Universe.

Search for Light Dark Matter from the Atmosphere in PandaX-4T.

We report a search for light dark matter produced through the cascading decay of η mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasielastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne·year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross section is set at 5.9×10^{-37} cm^{2} for a dark matter mass of 0.1 MeV/c^{2} and mediator mass of 300 MeV/c^{2}. The lowest upper limit of η to the dark matter decay branching ratio is 1.6×10^{-7}.

Search for Solar

A search for interactions from solar ^{8}B neutrinos elastically scattering off xenon nuclei using PandaX-4T commissioning data is reported. The energy threshold of this search is further lowered compared with the previous search for dark matter, with various techniques utilized to suppress the background that emerges from data with the lowered threshold. A blind analysis is performed on the data with an effective exposure of 0.48 tonne year, and no significant excess of events is observed. Among the results obtained using the neutrino-nucleus coherent scattering, our results give the best constraint on the solar ^{8}B neutrino flux. We further provide a more stringent limit on the cross section between dark matter and nucleon in the mass range from 3 to 9 GeV/c^{2}.

Search for Dark-Matter-Nucleon Interactions with a Dark Mediator in PandaX-4T.

We report results of a search for dark-matter-nucleon interactions via a dark mediator using optimized low-energy data from the PandaX-4T liquid xenon experiment. With the ionization-signal-only data and utilizing the Migdal effect, we set the most stringent limits on the cross section for dark matter masses ranging from 30 MeV/c^{2} to 2 GeV/c^{2}. Under the assumption that the dark mediator is a dark photon that decays into scalar dark matter pairs in the early Universe, we rule out significant parameter space of such thermal relic dark-matter model.

Receptor discordance among primary tumors, brain metastases and extra-brain metastases in patients with breast cancer.

Background: To investigate the expression status of estrogen receptor (ER), progesterone receptor (PR) and HER2 in patients with breast cancer brain metastases (BM). Methods: Patients who underwent craniotomy for BM were included. The status of ER, PR and HER2 (including HER2-low expression) in primary breast tumors (PT), BM and extra-BM (EM) was determined. Results: Between PT and BM, conversion of hormone receptor and HER2 occurred in 28% (30/107) and 12% (10/86) of cases. When considering three-tiered categorization of HER2, the conversion rate reached 31%. In the paired EM and BM (n = 39), the discordance rates were 18%, 3% and 22%, respectively. Conclusion: Receptor discordance was dynamic and relevant, especially using new HER2 categorization.

A clinical radiomics nomogram preoperatively to predict ductal carcinoma in situ with microinvasion in women with biopsy-confirmed ductal carcinoma in situ: a preliminary study.

PURPOSE: To predict ductal carcinoma in situ with microinvasion (DCISMI) based on clinicopathologic, conventional breast magnetic resonance imaging (MRI), and dynamic contrast enhanced MRI (DCE-MRI) radiomics signatures in women with biopsy-confirmed ductal carcinoma in situ (DCIS). METHODS: Eighty-six women with eighty-seven biopsy-proven DCIS who underwent preoperative MRI and underwent surgery were retrospectively identified. Clinicopathologic, conventional MRI, DCE-MRI radiomics, combine (based on conventional MRI and DCE-MRI radiomics), traditional (based on clinicopathologic and conventional MRI) and mixed (based on clinicopathologic, conventional MRI and DCE-MRI radiomics) models were constructed by logistic regression (LR) with a 3-fold cross-validation, all evaluated using receiver operating characteristic (ROC) curve analysis. A clinical radiomics nomogram was then built by incorporating the Radiomics score, significant clinicopathologic and conventional MRI features of mixed model. RESULTS: The area under the curves (AUCs) of clinicopathologic, conventional MRI, DCE-MRI radiomics, traditional, combine, and mixed model were 0.76 (95% confidence interval [CI] 0.59-0.94), 0.77 (95%CI 0.59-0.95), 0.74 (95%CI 0.55-0.93), 0.87 (95%CI 0.73-1), 0.8 (95%CI 0.63-0.96), and 0.93 (95%CI 0.84-1) in the validation cohort, respectively. The clinical radiomics nomogram based on mixed model showed higher AUCs than both clinicopathologic and DCE-MRI radiomics models in training/test (all P < 0.05) set and showed the greatest overall net benefit for upstaging according to decision curve analysis (DCA). CONCLUSION: A nomogram constructed by combining clinicopathologic, conventional MRI features and DCE-MRI radiomics signatures may be useful in predicting DCISMI from DICS preoperatively.

Quantifying spatially varying impacts of public transport on NO[Formula: see text] concentrations with big geo-data.

Anthropogenic NO[Formula: see text] concentrations cause climate change and human health issues. Previous studies have focused on the contribution of traffic factors to NO[Formula: see text] emissions but have ignored the spatially varying impact of public transport supply and demand on high-resolution NO[Formula: see text] concentrations. This study first applies a two-stage interpolation model to generate a high-resolution urban NO[Formula: see text] concentration map originating from satellite measurement products. Then, we formulate 12 explanatory indicators derived from a fusion of massive big geo-data including smart card data and point of interest information, to represent the specific degree of public transport supply and citizens' demand. Furthermore, a geographically weighted regression is applied to quantify the spatial variation in the effect of these indicators on the urban NO[Formula: see text] concentrations. The result shows that public transportation coverage, frequency, and capabilities as public transport supply indicators in metropolitan and suburban areas have a two-way influence on the NO[Formula: see text] emissions. However, among public transport demand indicators, the economic level has a significant positive impact in most areas. Our findings can provide policy implications for public transportation system optimization and air quality improvement.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter at the PandaX-II Experiment.

We report a novel search for the cosmic-ray boosted dark matter using the 100 tonne·day full dataset of the PandaX-II detector located at the China Jinping Underground Laboratory. With the extra energy gained from the cosmic rays, sub-GeV dark matter particles can produce visible recoil signals in the detector. The diurnal modulations in rate and energy spectrum are utilized to further enhance the signal sensitivity. Our result excludes the dark matter-nucleon elastic scattering cross section between 10^{-31} and 10^{-28} cm^{2} for dark matter masses from 0.1 MeV/c^{2} to 0.1 GeV/c^{2}, with a large parameter space previously unexplored by experimental collaborations.

First Search for the Absorption of Fermionic Dark Matter with the PandaX-4T Experiment.

Compared with the signature of dark matter elastic scattering off nuclei, the absorption of fermionic dark matter by nuclei opens up a new searching channel for light dark matter with a characteristic monoenergetic signal. In this Letter, we explore the 95.0-day data from the PandaX-4T commissioning run and report the first dedicated searching results of the fermionic dark matter absorption signal through a neutral current process. No significant signal was found, and the lowest limit on the dark matter-nucleon interaction cross section is set to be 1.5×10^{-50} cm^{2} for a fermionic dark matter mass of 40 MeV/c^{2} with 90% confidence level.

Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T.

We report a search on sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne year exposure collected by the PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and the electron. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such a dark matter candidate into photon final states. In particular, we present the first direct detection limits for a vector (axial-vector) interaction which are the strongest in the mass range from 35 to 55 (25 to 45) keV/c^{2} in comparison to other astrophysical and cosmological constraints.

Changes in Serum Enzymes and Related Mechanisms of Respiratory Dysfunction in Patients after Venomous Snake Bite and Analysis of Anti-Venomous Snake Serum Treatment.

To explore the changes in serum enzymes in patients with a snake bite, the treatment of respiratory dysfunction, and the clinical effect of anti-snake serum treatment. Fifty snake bite patients admitted to the emergency medicine department were selected and rolled into a light group (n=27), heavy group (n=15), and critical group (n=8). Anti-venomous snake serum was injected intravenously. Patients with severe respiratory dysfunction were treated with mechanical ventilation. The white blood cell (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) counts of the heavy group and the critical group were higher versus light group (P<0.05). The WBC, CRP, IL-6, ALT, AST, BUN, and Cr of the critical group were higher versus the heavy group (P<0.05). The prothrombin time (PT), activated partial thrombin time (APTT), and thrombin time (TT) of the heavy group and critical group were longer versus the light group (P<0.05). The PT, APTT, and TT of the critical group were longer than the heavy group (P<0.05). The fibrinogen (FIB) of the light group was higher in contrast to that in the other two groups (P<0.05), while the critical group was the lowest (P<0.05). In summary, the severity of snakebites in patients can be evaluated according to the indexes of WBC, IL-6, coagulation function, and liver and kidney function.

Toxoplasma gondii effector TgIST blocks type I interferon signaling to promote infection.

In contrast to the importance of type II interferon-γ (IFN-γ) in control of toxoplasmosis, the role of type I IFN is less clear. We demonstrate here that TgIST, a secreted effector previously implicated in blocking type II IFN-γ signaling, also blocked IFN-ß responses by inhibiting STAT1/STAT2-mediated transcription in infected cells. Consistent with a role for type I IFN in cell intrinsic control, ∆Tgist mutants were more susceptible to growth inhibition by murine and human macrophages activated with IFN-ß. Additionally, type I IFN was important for production of IFN-γ by natural killer (NK) cells and recruitment of inflammatory monocytes at the site of infection. Mice lacking type I IFN receptors (Ifnar1-/-) showed increased mortality following infection with wild-type parasites and decreased virulence of ∆Tgist parasites was restored in Ifnar1-/- mice. The findings highlight the importance of type I IFN in control of toxoplasmosis and illuminate a parasite mechanism to counteract the effects of both type I and II IFN-mediated host defenses.

Pretherapy platelet-to-lymphocyte ratio as a prognostic parameter for locally advanced hypopharyngeal cancer patients treated with radiotherapy combined with chemotherapy.

PURPOSE: This study aimed to identify whether the platelet-to-lymphocyte ratio (PLR) correlated with the prognosis of patients with locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) undergoing radiotherapy combined with chemotherapy. METHODS: This study enrolled 103 patients diagnosed with LA-HPSCC and treated with radiotherapy combined with chemotherapy between 2008 and 2021. The optimal PLR cut-off value was chosen from the receiver operating characteristic (ROC) curve analysis. According to the cut-off value of PLR, patients were divided into two groups: a low PLR group (< 133.06) and a high PLR group (≥ 133.06). Propensity score matching (PSM) was used to balance the confounding factors between the two PLR groups. Univariate and multivariate Cox proportional hazard regression models, the Kaplan-Meier curve by the log-rank test, and univariate and multivariate Fine-Gray competing risk models were all used for assessment. RESULTS: After PSM, 27 pairs were left, and the high PLR group correlated with higher local failure (sHR 6.91, 95% CI 2.14-22.35, p = 0.001) in the multivariate Fine-Gray competing risk model. Moreover, the low PLR group had a significantly longer 3-year progression-free survival (43.7% vs. 29.2%, p = 0.038) and overall survival (55.1% vs. 32.1%, p = 0.034) than the high PLR group had. Multivariate Cox analysis showed that a low PLR was an independent protective factor for PFS (HR 0.43, 95% CI 0.21-0.92, p = 0.019) and OS (HR 0.46, 95% CI 0.22-0.96, p = 0.039) in patients with LA-HPSCC. CONCLUSION: Pretherapy PLR might be a factor in predicting the risk of local failure and survival in LA-HPSCC patients undergoing radiotherapy combined with chemotherapy.

Shortening door-to-puncture time and improving patient outcome with workflow optimization in patients with acute ischemic stroke associated with large vessel occlusion.

OBJECTIVE: We aimed to evaluate door-to-puncture time (DPT) and door-to-recanalization time (DRT) without directing healthcare by neuro-interventionalist support in the emergency department (ED) by workflow optimization and improving patients' outcomes. METHODS: Records of 98 consecutive ischemic stroke patients who had undergone endovascular therapy (EVT) between 2018 to 2021 were retrospectively reviewed in a single-center study. Patients were divided into three groups: pre-intervention (2018-2019), interim-intervention (2020), and post-intervention (January 1st 2021 to August 16th, 2021). We compared door-to-puncture time, door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), last known normal time to-puncture time (LKNPT), and patient outcomes (measured by 3 months modified Rankin Scale) between three groups using descriptive statistics. RESULTS: Our findings indicate that process optimization measures could shorten DPT, DRT, PRT, and LKNPT. Median LKNPT was shortened by 70 min from 325 to 255 min(P < 0.05), and DPT was shortened by 119 min from 237 to 118 min. DRT shortened by 132 min from 338 to 206 min, and PRT shortened by 33 min from 92 to 59 min from the pre-intervention to post-intervention groups (all P < 0.05). Only 21.4% of patients had a favorable outcome in the pre-intervention group as compared to 55.6% in the interventional group (P= 0.026). CONCLUSION: This study demonstrated that multidisciplinary cooperation was associated with shortened DPT, DRT, PRT, and LKNPT despite challenges posed to the healthcare system such as the COVID-19 pandemic. These practice paradigms may be transported to other stroke centers and healthcare providers to improve endovascular time metrics and patient outcomes.