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Objective: The current study aimed to investigate the baseline immune and inflammatory features and in-hospital outcomes of patients infected with the Omicron variant (PIWO) who presented with different disease severities during the first wave of mass Omicron infections in the Chinese population has occurred. Method: A cross‐sectional study was conducted on 140 hospitalized PIWO between December 11, 2022, and February 16, 2023. The clinical features, antibodies against SARS-CoV-2, immune cells, and inflammatory cytokines among mildly, severely, and critically ill PIWO at baseline and during follow-up period were compared. Result: Patients with severe (n = 49) and critical (n = 35) disease were primarily male, needed invasive mechanical ventilation treatment, and exhibited higher mortality than those with mild disease (n = 56). During acute infection, SARS-CoV-2-specific antibody levels fluctuated with disease severity, serum antibodies increased and the incidence of severe cases decreased in critically ill PIWO over time. Antibody titers in severe or critical PIWO with no antibody responses at baseline did not increase significantly over time. Meanwhile, CD4+T cell, CD8+T cell, and natural killer cell counts were negatively correlated with disease severity, whereas interleukin (IL)-6 and IL-10 levels were positively correlated. In addition, combined diabetes, immunosuppressive therapy before infection, serum amyloid A, IL-10 and neutrophil counts were independently associated with severe and critical illness in PIWO. Among the 11 nonsurvivors, 8, 2, 1 died of respiratory failure, sudden cardiac death, and renal failure, respectively. Compared with survivors, nonsurvivors exhibited lower seropositivity of SARS-CoV-2-specific antibody, reduced CD3+T and CD4+T cell counts, and higher IL-2R, IL-6, IL-8, and IL-10 levels. Of note, lactate dehydrogenase was a significant risk factor of death in severe or critically ill PIWO. Conclusion: This present study assessed the dynamic changes of SARS-CoV-2-specific antibodies, immune cells and inflammatory indexes between severely and critically ill PIWO. Critical and dead PIWO featured compromised humoral immune response and excessive inflammation, which broadened the understanding of the pathophysiology of Omicron infection and provides warning markers for severe disease and poor prognosis. Highlights : 1. Specific anti-SARS-CoV-2 antibodies showed a trend of increasing first and then decreasing with the progression of disease severity. 2. The severity of infection decreased and the levels of the four antibodies against SARS-CoV-2 increased in critically ill PIWO over time. 3. Negative antibodies in severe/critical PIWO at baseline did not increase significantly with therapeutic intervention. 4. Dead PIWO exhibited disordered features of immunocompromised, hyperinflammatory, abnormal coagulation and myocardial injury. 5. Combined diabetes, immunosuppressive therapy before infection, high levels of SAA, IL-10 and neutrophil counts were the risk factors for severe/critical illness. 6. High LDH was related to death event in severely/critically ill PIWO. [ABSTRACT FROM AUTHOR]

Enteropathogenic E. coli (EPEC) and related enterobacteria rely on a type III secretion system (T3SS) effector NleE to block host NF-κB signaling. NleE is a first in class, novel S-adenosyl-L-methionine (SAM)-dependent methyltransferase that methylates a zinc-coordinating cysteine in the Npl4-like Zinc Finger (NZF) domains in TAB2/3 adaptors in the NF-κB pathway, but its mechanism of action and other human substrates are unknown. Here we solve crystal structure of NleE-SAM complex, which reveals a methyltransferase fold different from those of known ones. The SAM, cradled snugly at the bottom of a deep and narrow cavity, adopts a unique conformation ready for nucleophilic attack by the methyl acceptor. The substrate NZF domain can be well docked into the cavity, and molecular dynamic simulation indicates that Cys673 in TAB2-NZF is spatially and energetically favorable for attacking the SAM. We further identify a new NleE substrate, ZRANB3, that functions in PCNA binding and remodeling of stalled replication forks at the DNA damage sites. Specific inactivation of the NZF domain in ZRANB3 by NleE offers a unique opportunity to suggest that ZRANB3-NZF domain functions in DNA repair processes other than ZRANB3 recruitment to DNA damage sites. Our analyses suggest a novel and unexpected link between EPEC infection, virulence proteins and genome integrity.

A large group of bacterial virulence autotransporters including AIDA-I from diffusely adhering E. coli (DAEC) and TibA from enterotoxigenic E. coli (ETEC) require hyperglycosylation for functioning. Here we demonstrate that TibC from ETEC harbors a heptosyltransferase activity on TibA and AIDA-I, defining a large family of bacterial autotransporter heptosyltransferases (BAHTs). The crystal structure of TibC reveals a characteristic ring-shape dodecamer. The protomer features an N-terminal β-barrel, a catalytic domain, a β-hairpin thumb, and a unique iron-finger motif. The iron-finger motif contributes to back-to-back dimerization; six dimers form the ring through β-hairpin thumb-mediated hand-in-hand contact. The structure of ADP-D-glycero-β-D-manno-heptose (ADP-D,D-heptose)-bound TibC reveals a sugar transfer mechanism and also the ligand stereoselectivity determinant. Electron-cryomicroscopy analyses uncover a TibC–TibA dodecamer/hexamer assembly with two enzyme molecules binding to one TibA substrate. The complex structure also highlights a high efficient hyperglycosylation of six autotransporter substrates simultaneously by the dodecamer enzyme complex.

Digital watermarking is an effective way for authentication of stereo images when they are transmitted over networks. Since the left and right images of a stereo image pair are not independent but similar to each other, their watermarking design should be different from that of mono-images. This paper thus proposes a stereo matching based stereo image watermarking scheme for tamper detection and recovery. One-to-one mappings between left and right image blocks are established, and tamper detection bits generated from each block and the recovery bits of the mapped block are embedded back to the block itself. To keep the consistency between left and right images, a stereo image pair is usually tampered symmetrically. That is, the tampered areas in left and right images are similar to each other, thus the combination of tamper detection results of left and right images can facilitate more accurate tamper detection results. In general, a tampered block in one image of stereo image pair can be recovered with the recovery bits embedded in its mapped block in the other view. However, if the mapped block is also tampered, stereo matching based method is employed to recover the tampered block. Our experimental results show that the proposed tamper detection scheme can identify the tampered blocks with the probability of almost 1 if the stereo image is modified symmetrically. Moreover, the proposed scheme is able to recover a view of stereo images altered 100% which may even confuse the human eyes.

Background and objective Surgery is the best treatment for early and middle stage non-small cell lung cancer. The aim of this study is to summarize the experience of bronchial sleeve mordality lobectomy and carinal resection in the treatment of 92 patients with central lung cancer from January, 1996 to May, 2010. Methods A total of 92 patients with central lung cancer underwent pulmonary resection. Carinal resection and reconstruction were performed in 14 patients, bronchial sleeve resection in 70 patients, and bronchial sleeve combined with pulmonary artery sleeve lobectomy in 8 patients. Results There was no operative mortality. The average operation time was 2 hours and 43 minutes. Postoperative complications such as pulmonary atelectasis occurred in 6.94% (7/92) of total group, and hoarseness in 4.35% (4/92). The 1, 3 and 5 year survival rates were 80.7%, 59.6% and 31.5%. Conclusion Bronchial sleeve lobectomy and double sleeve lobectomy are capable of excising pulmonary tumor as much as possible while remaining healthy lung tissues. Carinal resection and reconstruction is helpful to extend the surgical indication, and increase the chance of successful resection.

BACKGROUND: The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Toll-like receptors (TLRs) are one of the receptor types of the body's innate immune system. The function of the TLR system and the mechanisms by which it functions in renal aging remain unclear. In the present study, we, for the first time, systematically investigated the role of the TLR system and the inflammation responses activated by TLRs during kidney aging. METHODS: We used western blot and immunohistochemistry to systematically analyze the changes in the expression and activation of the endogenous TLR ligands HSP70 and HMGB1, the TLRs (TLR1-TLR11), their downstream signaling pathway molecules MyD88 and Phospho-IRF-3, and the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα (NF-κB inhibition factor α), NF-κBp65, and Phospho-NF-κBp65 (activated NF-κB p65) in the kidneys of 3 months old (youth group), 12 months old (middle age group), and 24 months old (elderly group) rats. We used RT-qPCR to detect the mRNA expression changes of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b in the rat renal tissues of the various age groups. RESULTS: We found that during kidney aging, the HSP70 and HMGB1 expression levels were significantly increased, and the expression levels of TLR1, 2, 3, 4, 5, and 11 and their downstream signaling pathway molecules MyD88 and Phospho-IRF-3 were markedly elevated. Further studies have shown that in the aging kidneys, the expression levels of the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα, NF-κBp65, and Phospho-NF-κBp65 were obviously increased, and those of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b were significantly upregulated. CONCLUSIONS: These results showed that the TLR system might play an important role during the kidney aging process maybe by activating the NF-κB signaling pathway and promoting the high expression of inflammation factors.

To compress stereo video effectively, this paper proposes a novel macroblock (MB) level rate control method based on binocular perception. A binocular just-notification difference (BJND) model based on the parallax matching is first used to describe binocular perception. Then, the proposed rate control method is performed in stereo video coding with four levels, namely, view level, group-of-pictures (GOP) level, frame level, and MB level. In the view level, different proportions of bitrates are allocated for the left and right views of stereo video according to the prestatistical rate allocation proportion. In the GOP level, the total number of bitrates allocated to each GOP is computed and the initial quantization parameter of each GOP is set. In the frame level, the target bits allocated to each frame are computed. In the MB level, visual perception factor, which is measured by the BJND value of MB, is used to adjust the MB level bit allocation, so that the rate control results in line with the human visual characteristics. Experimental results show that the proposed method can control the bitrate more accurately and get better subjective quality of stereo video, compared with other methods.

We present a simple quality assessment index for stereoscopic images based on 3D gradient magnitude. To be more specific, we construct 3D volume from the stereoscopic images across different disparity spaces and calculate pointwise 3D gradient magnitude similarity (3D-GMS) along three horizontal, vertical, and viewpoint directions. Then, the quality score is obtained by averaging the 3D-GMS scores of all points in the 3D volume. Experimental results on four publicly available 3D image quality assessment databases demonstrate that, in comparison with the most related existing methods, the devised algorithm achieves high consistency alignment with subjective assessment.

Fragile histidine triad (FHIT) is a tumor suppressor protein that regulates cancer cell proliferation and apoptosis. However, its exact mechanism of action is poorly understood. Phosphatidylinositol 3-OH kinase (PI3K)-Akt-survivin is an important signaling pathway that was regulated by FHIT in lung cancer cells. To determine whether FHIT can regulate this pathway in cholangiocarcinoma QBC939 cells, we constructed an FHIT expression plasmid and used it to transfect QBC939 cells. Protein and mRNA expression were measured by western blotting and qRT-PCR, respectively. The viability and apoptosis of QBC939 cells were then assessed using MTT assays and flow cytometry. Our results revealed that the expression of survivin and Bcl-2 was downregulated, and caspase 3 was upregulated, in cells overexpressing FHIT. In addition, FHIT suppressed the phosphorylation of Akt. The changes in cell proliferation and apoptosis were obvious in cells overexpressing FHIT which parallels that of treatment with LY294002, a potent inhibitor of phosphoinositide 3-kinases. Treatment with LY294002 further decreased the expression of survivin and Bcl-2 and increased caspase-3 levels. These results suggest that FHIT can block the PI3K-Akt-survivin pathway by suppressing the phosphorylation of Akt and the expression of survivin and Bcl-2 and upregulating caspase 3.

BACKGROUND:Candida albicans (C. albicans), the most common human fungal pathogen, can cause fatal systemic infections under certain circumstances. Mannan-binding lectin (MBL),a member of the collectin family in the C-type lectin superfamily, is an important serum component associated with innate immunity. Toll-like receptors (TLRs) are expressed extensively, and have been shown to be involved in C. albicans-induced cellular responses. We first examined whether MBL modulated heat-killed (HK) C. albicans-induced cellular responses in phorbol 12-myristate 13-acetate (PMA)-activated human THP-1 macrophages. We then investigated the possible mechanisms of its inhibitory effect. METHODOLOGY/PRINCIPAL FINDING:Enzyme-linked immunosorbent assay (ELISA) and reverse transcriptasepolymerase chain reaction (RT-PCR) analysis showed that MBL at higher concentrations (10-20 µg/ml) significantly attenuated C. albicans-induced chemokine (e.g., IL-8) and proinflammatory cytokine (e.g., TNF-α) production from PMA-activated THP-1 cells at both protein and mRNA levels. Electrophoretic mobility shift assay (EMSA) and Western blot (WB) analysis showed that MBL could inhibit C. albicans-induced nuclear factor-κB (NF-κB) DNA binding and its translocation in PMA-activated THP-1 cells. MBL could directly bind to PMA-activated THP-1 cells in the presence of Ca(2+), and this binding decreased TLR2 and TLR4 expressions in C. albicans-induced THP-1 macrophages. Furthermore, the binding could be partially inhibited by both anti-TLR2 monoclonal antibody (clone TL2.1) and anti-TLR4 monoclonal antibody (clone HTA125). In addition, co-immunoprecipitation experiments and microtiter wells assay showed that MBL could directly bind to the recombinant soluble form of extracellular TLR2 domain (sTLR2) and sTLR4. CONCLUSIONS/SIGNIFICANCE:Our study demonstrates that MBL can affect proinflammatory cytokine and chemokine expressions by modifying C. albicans-/TLR-signaling pathways. This study supports an important role for MBL on the regulation of C. albicans-induced cellular responses.

The genus Shigella infects human gut epithelial cells to cause diarrhea and gastrointestinal disorders. Like many other Gram-negative bacterial pathogens, the virulence of Shigella spp. relies on a conserved type three secretion system that delivers a handful of effector proteins into host cells to manipulate various host cell physiology. However, many of the Shigella type III effectors remain functionally uncharacterized. Here we observe that OspG, one of the Shigella effectors, interacted with ubiquitin conjugates and poly-ubiquitin chains of either K48 or K63 linkage in eukaryotic host cells. Purified OspG protein formed a stable complex with ubiquitin but showed no interactions with other ubiquitin-like proteins. OspG binding to ubiquitin required the carboxyl terminal helical region in OspG and the canonical I44-centered hydrophobic surface in ubiquitin. OspG and OspG-homologous effectors, NleH1/2 from enteropathogenic E coli (EPEC), contain sub-domains I-VII of eukaryotic serine/threonine kinase. GST-tagged OspG and NleH1/2 could undergo autophosphorylation, the former of which was significantly stimulated by ubiquitin binding. Ubiquitin binding was also required for OspG functioning in attenuating host NF-κB signaling. Our data illustrate a new mechanism that bacterial pathogen like Shigella exploits ubiquitin binding to activate its secreted virulence effector for its functioning in host eukaryotic cells.

Upon phagocytosis, Legionella pneumophila translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity, ultimately establishing intracellular survival and growth. VipD of L. pneumophila belongs to a family of bacterial effectors that contain the N-terminal lipase domain and the C-terminal domain with an unknown function. We report the crystal structure of VipD and show that its C-terminal domain robustly interferes with endosomal trafficking through tight and selective interactions with Rab5 and Rab22. This domain, which is not significantly similar to any known protein structure, potently interacts with the GTP-bound active form of the two Rabs by recognizing a hydrophobic triad conserved in Rabs. These interactions prevent Rab5 and Rab22 from binding to downstream effectors Rabaptin-5, Rabenosyn-5 and EEA1, consequently blocking endosomal trafficking and subsequent lysosomal degradation of endocytic materials in macrophage cells. Together, this work reveals endosomal trafficking as a target of L. pneumophila and delineates the underlying molecular mechanism.

Reaction of 1,2-bis(diphenylphosphino)benzene (dppbz) with PhpdtFe2(CO)6 (A) in hot acetonitrile yielded a chelated complex, PhpdtFe2(CO)4(κ2-dppbz) (1), in moderate yield. Further treatment using an excess of HBF4·Et2O resulted in the protonation of 1 at room temperature in dichloromethane solution, forming a hydride [Phpdt(μ-H)Fe2(CO)4(κ2-dppbz)]BF4 (2). The chemical structures of both complexes were fully characterized by spectroscopic methods and X-ray crystallography, and the electronic structures were further investigated by UV-vis spectroscopy. The cyclic voltammetry (CV) of 1 in the absence and presence of acetic acid were also investigated. [ABSTRACT FROM AUTHOR]

Accurate accounting of emissions and removals of CO 2 is critical for the planning and verification of emission reduction targets in support of the Paris Agreement. Here, we present a pilot dataset of country-specific net carbon exchange (NCE; fossil plus terrestrial ecosystem fluxes) and terrestrial carbon stock changes aimed at informing countries' carbon budgets. These estimates are based on "top-down" NCE outputs from the v10 Orbiting Carbon Observatory (OCO-2) modeling intercomparison project (MIP), wherein an ensemble of inverse modeling groups conducted standardized experiments assimilating OCO-2 column-averaged dry-air mole fraction (XCO2) retrievals (ACOS v10), in situ CO 2 measurements or combinations of these data. The v10 OCO-2 MIP NCE estimates are combined with "bottom-up" estimates of fossil fuel emissions and lateral carbon fluxes to estimate changes in terrestrial carbon stocks, which are impacted by anthropogenic and natural drivers. These flux and stock change estimates are reported annually (2015–2020) as both a global 1 ∘ × 1 ∘ gridded dataset and a country-level dataset and are available for download from the Committee on Earth Observation Satellites' (CEOS) website: 10.48588/npf6-sw92. Across the v10 OCO-2 MIP experiments, we obtain increases in the ensemble median terrestrial carbon stocks of 3.29–4.58 PgCO2yr-1 (0.90–1.25 PgCyr-1). This is a result of broad increases in terrestrial carbon stocks across the northern extratropics, while the tropics generally have stock losses but with considerable regional variability and differences between v10 OCO-2 MIP experiments. We discuss the state of the science for tracking emissions and removals using top-down methods, including current limitations and future developments towards top-down monitoring and verification systems. [ABSTRACT FROM AUTHOR]

Itaconate has emerged as a novel anti-inflammatory and antioxidative endogenous metabolite, yet its role in allergic airway inflammation (AAI) and the underlying mechanism remains elusive. Here, the itaconate level in the lung was assessed by High Performance Liquid Chromatography (HPLC), and the effects of the Irg1/itaconate pathway on AAI and alveolar macrophage (AM) immune responses were evaluated using an ovalbumin (OVA)-induced AAI model established by wild type (WT) and Irg1−/− mice, while the mechanism of this process was investigated by metabolomics analysis, mitochondrial/cytosolic protein fractionation and transmission electron microscopy in the lung tissues. The results demonstrated that the Irg1 mRNA/protein expression and itaconate production in the lung were significantly induced by OVA. Itaconate ameliorated while Irg1 deficiency augmented AAI, and this may be attributed to the fact that itaconate suppressed mitochondrial events such as NLRP3 inflammasome activation, oxidative stress and metabolic dysfunction. Furthermore, we identified that the Irg1/itaconate pathway impacted the NLRP3 inflammasome activation and oxidative stress in AMs. Collectively, our findings provide evidence for the first time, supporting the conclusion that in the allergic lung, the itaconate level is markedly increased, which directly regulates AMs’ immune responses. We therefore propose that the Irg1/itaconate pathway in AMs is a potential anti-inflammatory and anti-oxidative therapeutic target for AAI.

Inference of CO2 surface fluxes using atmospheric CO2 observations in atmospheric inversions depends critically on accurate representation of atmospheric transport. Here we characterize regional‐scale CO2 transport uncertainties due to uncertainties in meteorological fields using a mesoscale atmospheric model and an ensemble of simulations with flow‐dependent transport errors. During a 1‐month summer period over North America, transport uncertainties yield an ensemble spread in instantaneous CO2 at 100 m above ground level comparable to the CO2 uncertainties resulting from 48% relative uncertainty in 3‐hourly natural CO2 fluxes. Temporal averaging reduces transport uncertainties but increases the influence of CO2 uncertainties from the lateral boundaries. The influence of CO2 background uncertainties is especially large for column‐averaged CO2. These results suggest that transport errors and CO2 background errors limit regional atmospheric inversions at two distinct timescales and that the error characteristics of transport and background errors should guide the design of regional inversion systems. Plain Language Summary: Accurate estimates of regional‐scale CO2 surface fluxes are essential to improve our understanding of the carbon cycle and to verify human CO2 emission inventories. CO2 surface fluxes can be inferred from atmospheric CO2 measurements through inversion methods, which use atmospheric transport models to relate CO2 concentration to fluxes. However, previous studies have shown that inversion results can be sensitive to errors in the simulated atmospheric transport. To better understand how to account for such transport errors, we characterize the uncertainties in simulated CO2 concentration due to uncertainties in atmospheric transport by running an ensemble of perturbed transport simulations in a regional atmospheric model. Our results show that CO2 uncertainties due to transport uncertainties are about half the magnitude as uncertainties due to erroneous CO2 surface fluxes while displaying similar spatial and temporal patterns. Transport uncertainties are reduced when CO2 is time averaged, but at the same time the influence of uncertainties in the CO2 background concentration is increased at longer timescales. Thus, the flux signals in regional inversions are degraded by transport errors and CO2 background errors at different timescales, and it is imperative to properly account for these errors to obtain reliable regional‐scale CO2 flux estimates. Key Points: We quantify CO2 transport uncertainties due to uncertainties in meteorological fields at the regional scale and submonthly timescalesAtmospheric CO2 estimates that are strongly influenced by CO2 surface fluxes tend to also have large transport uncertaintiesThe signal‐to‐noise ratio in in situ CO2 is limited by transport errors at subweekly timescales and CO2 background errors at longer scales [ABSTRACT FROM AUTHOR]

N-nitrosodimethylamine (NDMA) is formed during ozonation of model compounds with dimethylhydrazine groups, such as daminozide (DMZ) and 2-furaldehyde 2,2-dimethylhydrazone (2-F-DMH) at pH 7 with yields of 100 % and 87 %, respectively. In this study, ozone/hydrogen peroxide (O 3 /H 2 O 2) and ozone/peroxymonosulfate (O 3 /PMS) were investigated to control NDMA formation, and O 3 /PMS (50–65 %) was more effective than O 3 /H 2 O 2 (10–25 %) with a ratio of H 2 O 2 or PMS to O 3 of 8:1. The reaction of PMS or H 2 O 2 to decompose ozone could not compete with the ozonation of model compound because of the high second-order rate constants of the ozonation of DMZ (5 ×105 M−1 s−1) or 2-F-DMH (1.6 ×107 M−1 s−1). The R ct value of the sulfate radical (SO 4 •−) showed a linear relationship with NDMA formation, indicating that SO 4 •− significantly contributed to its control. NDMA formation could be further controlled by injecting small quantities of ozone numerous times to minimize the dissolved ozone concentration. The effects of tannic acid, bromide and bicarbonate on NDMA formation were also investigated during ozonation, O 3 /H 2 O 2 , and O 3 /PMS processes. Bromate formation was more pronounced in the O 3 /PMS process than in the O 3 /H 2 O 2 process. Therefore, in practical applications of O 3 /H 2 O 2 or O 3 /PMS processes, the generation of NDMA and bromate should be detected. [Display omitted] • NDMA is formed during ozonation of N,N-dimethylhydrazine organics with high yields. • NDMA formation control is more efficiently by O 3 /PMS process than O 3 /H 2 O 2 process. • Removal of NDMA formation in O 3 /PMS process is correlated to the R ct value of SO 4 •-. • Bromide enhances NDMA formation during O 3 /PMS process with low dosage of PMS. • NDMA formation control and bromate formation promotion are found in O 3 /PMS process. [ABSTRACT FROM AUTHOR]

The adult kidney plays a central role in erythropoiesis and is the main source of erythropoietin (EPO), an oxygen-sensitive glycoprotein that is essential for red blood cell production. Decreases of renal pO2 promote hypoxia-inducible factor 2-mediated (HIF-2-mediated) induction of EPO in peritubular interstitial fibroblast-like cells, which serve as the cellular site of EPO synthesis in the kidney. It is not clear whether HIF signaling in other renal cell types also contributes to the regulation of EPO production. Here, we used a genetic approach in mice to investigate the role of renal epithelial HIF in erythropoiesis. Specifically, we found that HIF activation in the proximal nephron via induced inactivation of the von Hippel-Lindau tumor suppressor, which targets the HIF-α subunit for proteasomal degradation, led to rapid development of hypoproliferative anemia that was associated with a reduction in the number of EPO-producing renal interstitial cells. Moreover, suppression of renal EPO production was associated with increased glucose uptake, enhanced glycolysis, reduced mitochondrial mass, diminished O2 consumption, and elevated renal tissue pO2. Our genetic analysis suggests that tubulointerstitial cellular crosstalk modulates renal EPO production under conditions of epithelial HIF activation in the kidney. [ABSTRACT FROM AUTHOR]

Kidney size adaptively increases as mammals grow and in response to the loss of 1 kidney. It is not clear how kidneys size themselves or if the processes that adapt kidney mass to lean body mass also mediate renal hypertrophy following unilateral nephrectomy (UNX). Here, we demonstrated that mice harboring a proximal tubule-specific deletion of Pten (PtenptKO) have greatly enlarged kidneys as the result of persistent activation of the class I PI3K/mTORC2/AKT pathway and an increase of the antiproliferative signals p21 Cip1/WAF and p27 Kip1. Administration of rapamycin to PtenptKO mice diminished hypertrophy. Proximal tubule-specific deletion of Egfr in PtenptKO mice also attenuated class I PI3K/mTORC2/AKT signaling and reduced the size of enlarged kidneys. In PtenptKO mice, UNX further increased mTORC1 activation and hypertrophy in the remaining kidney; however, mTORC2-dependent AKT phosphorylation did not increase further in the remaining kidney of PtenptKO mice, nor was it induced in the remaining kidney of WT mice. After UNX, renal blood flow and amino acid delivery to the remaining kidney rose abruptly, followed by increased amino acid content and activation of a class III PI3K/mTORC1/S6K1 pathway. Thus, our findings demonstrate context-dependent roles for EGFR-modulated class I PI3K/mTORC2/AKT signaling in the normal adaptation of kidney size and PTEN-independent, nutrient-dependent class III PI3K/mTORC1/S6K1 signaling in the compensatory enlargement of the remaining kidney following UNX. [ABSTRACT FROM AUTHOR]

This paper reports density and viscosity data at T = 298.15, 303.15, 308.15, 313.15, and 318.15 K and surface tension data at 298.15 K for the binary system 1,2-ethanediamine (EDA) + diethylene glycol (DEG) as a function of composition under atmospheric pressure. From the experimental density and viscosity data, the excess molar volume and viscosity deviation were calculated, and the results were fitted to a Redlich-Kister equation to obtain the coefficients and to estimate the standard deviations between the experimental and calculated quantities. Based on the kinematic viscosity data, enthalpy of activation for viscous flow, entropy of activation for the viscous flow, and Gibbs energies of activation of viscous flow were calculated. In addition, based on Fourier transform infrared spectra, UV-vis spectra, and electrical conductivity for the system EDA + DEG with various concentrations, intermolecular interaction of EDA with DEG was discussed [ABSTRACT FROM AUTHOR]

NASA's Orbiting Carbon Observatory-3 (OCO-3) was designed to support the quantification and monitoring of anthropogenic CO 2 emissions. Its Snapshot Area Map (SAM) and target mode measurements provide an innovative dataset for carbon studies on sub-city scales. Unlike any other current space-based instrument, OCO-3 has the ability to scan large contiguous areas of emission hot spots like cities, power plants, and volcanoes. These measurements result in dense, fine-scale spatial maps of column averaged dry-air mole fractions of carbon dioxide (X CO 2). For the first time, we present and analyze X CO 2 distributions over the Los Angeles megacity (LA) derived from OCO-3 SAM and target mode observations. Urban X CO 2 enhancements range from 0 − 6 ppm (median enhancements ≃ 2 ppm) relative to a clean background and show excellent agreement with nearby ground-based TCCON measurements of X CO 2. OCO-3's dense observations reveal intra-urban variations of X CO 2 over the city that have never been observed from space before. The spatial variations are mainly driven by the complex fossil fuel emission patterns and meteorological conditions in the LA Basin and are in good agreement with those from co-located TROPOMI measurements of co-emitted NO 2. Differences between measured and simulated X CO 2 enhancements from two models (WRF-Chem and X-STILT) are typically below 1 ppm with larger differences for some sub regions. Both models capture the observed intra-urban X CO 2 gradients. Further, OCO-3's multi-swath measurements capture about three times as much of the city emissions compared to single-swath overpasses. OCO-3's frequent target and SAM mode observations will pave the way to constrain urban emissions at finer, sub-city scales. [ABSTRACT FROM AUTHOR]

• Estrogen-related and Immune-related genes were related with chemosensitivity in breast cancers. • 17-gene prediction model using a Naive Bayes algorithm had good performance to predict chemosensitivity in breast cancers. • 17-gene prediction model also had better performance than IHC4 score in prediction of chemosensitivity. Chemotherapy is useful to many breast cancer patients, however, it is not therapeutic for some patients. Pathologic complete response (pCR) is an indicator to good response in Neoadjuvant chemotherapy (NAC). In this study, we aimed to develop a way to predict pCR before NAC. We retrospectively collected 287 stage II-III breast cancer cases either to a training set (N = 197) or to a test set (N = 90). Fourteen candidate genes were selected from four public microarray data sets. A prediction model was built, by using these fourteen candidate genes and three reference genes expression which were tested by TaqMan probe-based quantitative polymerase chain reaction, after selecting a better algorithm. The Naive Bayes algorithm had a relatively higher predictive value, compared with random forest, support vector machine (SVM), and k-nearest neighbor (knn) algorithms (P < 0.05). This 17-gene prediction model showed a high positive correlation with pCR (odds ratio, 8.914, 95% confidence interval, 4.430–17.934, P < 0.001). By using this model, the enrolled patients were classified into sensitive (SE) and insensitive (INS) groups. The pCR rates between the SE and INS groups were highly different (42.3% vs.7.6%, P < 0.001). The sensitivity and specificity of this prediction model were 84.5% and 62.0%. Instead of whole transcriptome-based technologies, panel gene expression with tens of essential genes implemented in a machine learning model has predictive potential for chemosensitivity in breast cancers. [ABSTRACT FROM AUTHOR]

In this research, a novel structure of methanol cracking device was designed for methanol decomposition by using internal combustion (IC) engine exhaust heat. To evaluate and optimize its performance, the flow and heat transfer processes in methanol cracking device were investigated by computational fluid dynamics (CFD) simulation. The results show that methanol flow rate has important effects on the pressure loss, temperature distribution and heat flux. In general, the flow velocity and pressure in methanol cracking device are not well-proportioned and it results in the asymmetrical distributions of temperature and heat transfer coefficient. The maximum heat transfer coefficient is close to 100 W/(m2·K) while the minimum almost equals to zero because of flow stagnant zone. The average heat transfer coefficient increases as methanol flow rate rises, and it reaches to 51.63 W/(m2·K) at the methanol flow rate of 0.06 kg/s. When methanol flow rate increases from 0.03 kg/s to 0.06 kg/s, the average outlet temperature decreases from 615 K to 560 K and meets the requirements for methanol cracking reaction. All these indicate that the designed methanol cracking device can be used for IC engine exhaust heat cracking methanol, and also provide theoretical guidance for further optimizing the geometry structure. • A novel methanol cracking device with compact geometric structure was designed. • The flow and heat transfer processes of methanol vapor were studied systematically. • Methanol flow rate has important effects on temperature, heat flux and specific entropy filed. • The maximum heat transfer coefficient is close to 100 W/(m2·K) and appears in Zone H. • The minimum heat flux appears in Zone F due to the minimum heat transfer coefficient. [ABSTRACT FROM AUTHOR]

Background: As an important part in medical training in graduate school, 33-month medical residency training could be a stressful period inducing burnout (i.e. emotional exhaustion, depersonalization, and low personal accomplishment). Despite that existing literature has found that sense of belonging may have merits for residents' well-being, it has remained unclear how sense of school belonging affects burnout and the potential moderators. To address this question, a cross-sectional survey has been conducted among the residents of the physicians standardized residency training program in China., Methods: Seven hundred ( N  = 700) resident physicians from different majors (i.e. clinical medicine, clinical Stomatology, and Chinese medicine) and grades have participated in the survey. Resident's sense of school belonging was assessed with the psychological sense of school membership scale (PSSM, mean = 45.12, SD = 11.14). Burnout was measured by the 22-item Maslach Burnout Inventory (MBI-HSS, mean = 65.80, SD = 15.89), including three subscales of emotional exhaustion, depersonalization, and personal accomplishment., Results: The results showed that over 80% of the residents reported moderate or high level of emotional exhaustion and reduced personal accomplishment during residency training. Meanwhile, higher level of sense of school belonging was associated with lower overall burnout (B = -0.722, p  < 0.001), less emotional exhaustion, reduced depersonalization, and higher personal accomplishment. In particular, the benefits of sense of belonging seem more pronounced among female and those at earlier stage of residency. No interaction effect was found between sense of belonging and major, while those from Chinese medicine reported lower scores in overall burnout and the three dimensions., Conclusions: Burnout was a prevalent issue among the resident physicians, and our findings confirmed the protective effects of sense of school belonging against burnout. Therefore, support service should be developed to cultivate resident's sense of school belonging and social connections, particularly for female and those at earlier stage of residency.

Rationale: Hormone receptor-positive, HER2-negative advanced breast cancer complicated by pulmonary lymphangitic carcinomatosis (PLC) poses significant therapeutic challenges due to the lack of standardized treatment protocols. Despite various therapeutic interventions and supportive care, prognosis remains dismal., Patient Concerns: Herein, a 48-year-old Chinese woman presented with a persistent cough, unresponsive to anti-infective treatment for 1 month. A computed tomography (CT) scan revealed lymphatic vessel infiltration and a diffuse nodular pattern, suggestive of PLC., Diagnoses: Hormone receptor-positive, HER2-negative advanced breast cancer complicated by PLC., Interventions: The patient was treated with a regimen comprising low-dose apatinib, capecitabine, and albumin-bound paclitaxel., Outcomes: The patient achieved a partial response, with a progression-free survival exceeding beyond ten months. Symptoms of dyspnea and dry cough significantly improved, alongside a notable reduction in lymphangitic carcinomatosis., Lessons: This case highlights the potential antitumor activity of apatinib in breast cancer patients with presenting with PLC. While further studies are necessary, this therapeutic approach could represent a viable option for managing breast cancer in the context of a visceral crisis. The case also emphasizes the importance of individualized treatment strategies and further research to substantiate these promising findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Microsecretory adenocarcinoma (MSA) is a new type of salivary gland neoplasm identified in the 2022 World Health Organization Classification of Head and Neck Tumour (Skalova et al., Head Neck Pathol 16:40-53, 2022) and is characterized by a unique set of histomorphologic and immunohistochemical features and a recurrent MEF2C::SS18 fusion. MSA was initially misdiagnosed as another salivary gland tumour due to its similar morphology; until recently, only fewer than 50 cases were reported. We present a case of MSA of the hard palate with diverse architectural growth patterns, bland cytological features, abundant basophilic intraluminal secretions and fibromyxoid stroma. The tumour cells were positive for the SOX10, S100, and p63 protein and negative for the p40 protein according to immunohistochemistry. SS18 gene rearrangement was demonstrated via break-apart fluorescence in situ hybridization. We also provided a comprehensive literature review and integrated the clinicopathological features, immunophenotype, and molecular alterations of the disease. A comprehensive understanding of MSA enables us to accurately distinguish and categorize MSA from other salivary gland tumours with analogous morphologies., (© 2024. The Author(s).)

Background: Amide proton transfer (APT) imaging has been increasingly applied in tumor characterization. However, its value in evaluating breast cancer remains undetermined., Purpose: To assess the diagnostic performance of APT imaging in breast cancer and its association with prognostic histopathologic characteristics., Study Type: Prospective., Subjects: Eighty-four patients with breast lesions., Field Strength/sequence: A 3.0 T/single-shot fast spin echo APT imaging., Assessment: APTw signal in breast lesion was quantified. Lesion malignancy, T stage, grades, Ki-67 index, molecular biomarkers (estrogen receptor [ER] expression, progesterone receptor [PR] expression, human epidermal growth factor receptor [HER-2] expression), molecular subtypes (luminal A, luminal B, triple negative, and HER-2 enriched) were determined., Statistical Tests: Student t-test, one-way analysis of variance, receiver operating characteristic analysis, and Pearson's correlation with P < 0.05 as statistical significance., Results: APTw signal was significantly higher in malignant lesions (1.55% ± 1.24%) than in benign lesions (0.54% ± 1.13%), and in grade III lesions than in grade II lesions (1.65% ± 0.84% vs. 0.96% ± 0.96%), and in T2- (1.57% ± 0.64%) and T3-stage lesions (1.54% ± 0.63%) than in T1-stage lesions (0.81% ± 0.64%) for invasive breast carcinoma of no special type. APTw signal significantly correlated with Ki-67 index (r = 0.364) but showed no significant difference in groups of ER (P = 0.069), PR (P = 0.069), HER-2 (P = 0.961), and among molecular subtypes (P = 0.073)., Data Conclusion: APT imaging shows potential in differentiating breast lesion malignancy and associates with prognosis-related tumor grade, T stage, and proliferative activity., Evidence Level: 2 TECHNICAL EFFICACY: Stage 2., (© 2022 International Society for Magnetic Resonance in Medicine.)

In this study, expanded graphite (EG) was prepared by the oxidation and intercalation of the natural flake graphite using perchloric acid and potassium permanganate at different expansion temperatures (300, 400, 500, and 600°C), and were characterized by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). EG prepared at 500°C was found to be highly effective for the mineralization of oxalic acid aqueous solution during ozonation at pH 3, which was ascribed to the formation of hydroxyl radicals from the surface reaction of surface hydroxyl groups on EG with ozone. The performance of expanded graphite in this catalytic system was basically unchanged after three repeated use. The presence of Cl - , SO 4 2 - , HPO 4 2 - / H 2 PO 4 - and NO 3 - could inhibit the degradation of oxalic acid in catalytic ozonation with EG. Degradations of oxamic acid and pyruvic acid in catalytic ozonation with EG were pH-dependent, which were lower than that of oxalic acid. The degradations of oxalic acid and oxamic acid were identified as mineralization process by the determination of TOC, while pyruvic acid may transform into organic products such as acetic acid by O 3 /EG. Manganese ion (Mn 2+ ) could promote the degradation of oxalic acid by O 3 /EG at pH 3 because permanganate was produced by O 3 /EG in oxalic acid solution and then reacted with oxalic acid readily at acidic pH. Catalytic ozonation by EG exhibited great application potential for the destruction of refractory organic compounds.

Objective: To investigate the invasive capability and other clinicopathological features of conventional papillary thyroid carcinoma (CVPTC) with intraglandular lymphatic dissemination., Methods: Seventy-three conventional papillary thyroid carcinoma patients receiving total thyroidectomy were analyzed in this study. The expression of BRAF-V600E, D2-40 and CD31 in all thyroid samples was detected by immunohistochemical staining. The results were evaluated by two pathologists and were statistically analyzed. The rate of positive BRAF-V600E expression and the clinical invasiveness of CVPTC with intraglandular dissemination, multifocal non-intraglandular dissemination-CVPTC and single focus-CVPTC were evaluated. The correlation between BRAF-V600E expression, lymphatic vessel density, microvessel density and the clinicopathological characteristics of conventional papillary thyroid carcinoma were assessed., Results: Twenty-five intraglandular dissemination-CVPTC, 17 multifocal non-intraglandular dissemination-CVPTC and 31 single focus-CVPTC cases were included in this study. The results showed that BRAF-V600E expression was independently correlated with intraglandular dissemination, age and pN staging (P < 0.05). The lymphatic vessel density in the intraglandular dissemination-CVPTC group was higher than that in the non-intraglandular dissemination-CVPTC group (P < 0.05). Compared with cases without intraglandular dissemination, intraglandular dissemination-CVPTC was associated with a younger age, higher lymph node metastasis rate, pN staging, the expression of BRAF-V600E and increased Capsule invasion and lymphovascular tumor thrombus (P < 0.05). During the follow-up of 30 months (median 15 months), two patients in the intraglandular dissemination-CVPTC group had cervical lymph node metastasis after the first operation., Conclusions: Intraglandular dissemination-CVPTC shows more aggressive features, and intraglandular lymphatic dissemination may be a potential biological indicator of poor prognosis., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

China's Clinical Medicine Level Test (CMLT) was designed to evaluate the key factors that affect the learning outcome of medical students prior to entering clinical practice. In this study, we systemically analyzed the performance of a cohort of medical students at Jinan University School of Medicine participating in the recent CMLT. The analytical results of the medical students' written and objective structured clinical examination (OSCE) scores showed that their academic performance was predominantly associated with students' internship allocations, although other demographic characteristics such as sex, age, geographical origin of students, and grade point average (GPA) might be sporadically related to the students' OSCE performance at different OSCE stations. To explore the inherent reasons behind this, a survey was implemented among the medical students who participated in the examination to further interpret the factors influencing the students' learning outcome. The findings of this questionnaire manifested that intrinsic motivation and identified regulation acted as the major motivational profiles for the medical students from three different internship sites, whereas external regulation emerged as the crucial factor to make the students perform well academically in the CMLT. The result of this study suggested that strengthening the quality control of the clinical learning environment and improving medical administration may still be the most effective approaches to ensure the quality of clinical medical education.

Frontal boundaries have been shown to cause large changes in CO 2 mole-fractions, but clouds and the complex vertical structure of fronts make these gradients difficult to observe. It remains unclear how the column average CO 2 dry air mole-fraction (XCO 2 ) changes spatially across fronts, and how well airborne lidar observations, data assimilation systems, and numerical models without assimilation capture XCO 2 frontal contrasts (ΔXCO 2, i.e., warm minus cold sector average of XCO 2 ). We demonstrated the potential of airborne Multifunctional Fiber Laser Lidar (MFLL) measurements in heterogeneous weather conditions (i.e., frontal environment) to investigate the ΔXCO 2 during four seasonal field campaigns of the Atmospheric Carbon and Transport-America (ACT-America) mission. Most frontal cases in summer (winter) reveal higher (lower) XCO 2 in the warm (cold) sector than in the cold (warm) sector. During the transitional seasons (spring and fall), no clear signal in ΔXCO 2 was observed. Intercomparison among the MFLL, assimilated fields from NASA's Global Modeling and Assimilation Office (GMAO), and simulations from the Weather Research and Forecasting--Chemistry (WRF-Chem) showed that (a) all products had a similar sign of ΔXCO 2 though with different levels of agreement in ΔXCO 2 magnitudes among seasons; (b) ΔXCO 2 in summer decreases with altitude; and (c) significant challenges remain in observing and simulating XCO 2 frontal contrasts. A linear regression analyses between ΔXCO 2 for MFLL versus GMAO, and MFLL versus WRF-Chem for summer-2016 cases yielded a correlation coefficient of 0.95 and 0.88, respectively. The reported ΔXCO 2 variability among four seasons provide guidance to the spatial structures of XCO 2 transport errors in models and satellite measurements of XCO 2 in synoptically-active weather systems., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2022. The Authors.)

The COVID-19 pandemic is impacting human activities, and in turn energy use and carbon dioxide (CO 2 ) emissions. Here we present daily estimates of country-level CO 2 emissions for different sectors based on near-real-time activity data. The key result is an abrupt 8.8% decrease in global CO 2 emissions (-1551 Mt CO 2 ) in the first half of 2020 compared to the same period in 2019. The magnitude of this decrease is larger than during previous economic downturns or World War II. The timing of emissions decreases corresponds to lockdown measures in each country. By July 1st, the pandemic's effects on global emissions diminished as lockdown restrictions relaxed and some economic activities restarted, especially in China and several European countries, but substantial differences persist between countries, with continuing emission declines in the U.S. where coronavirus cases are still increasing substantially.

This study assessed the public's health risk awareness of urban air pollution triggered by three megacities in China, and the data are the responses from a sample size of 3868 megacity inhabitants from Shanghai, Nanchang and Wuhan. Descriptive analyses were used to summarize the respondents' demographics, perceived health risks from air pollution and sources of health-related knowledge on urban air pollution. Chi-square tests were used to examine if participants' demographics were associated with participant's general attitudes towards current air quality and the three perceived highest health risks due to urban air pollution. We found low rate of satisfaction of current urban air quality as well as poor knowledge of air pollution related indicator. Participants' gender, age and travel experience were found to be associated with the satisfaction of current air quality. The knowledge of air pollution related indicator was significantly affected by respondents' education, monthly income, health status, and sites of study. As many as 46.23% of the participants expressed their feelings of anxiety when exposed to polluted air, especially females, older adults and those with poor health conditions. Most participants believed that coughs/colds, eye problems and skin allergies were the three highest health risks due to urban air pollution based on public education through television/radio, internet and newspaper/magazine. Further public health education is needed to improve public awareness of air pollution and its effects., Competing Interests: The authors declare no conflict of interest.

Tobacco use is a global health problem, including in Taiwan. The present study evaluated the perceived risk of smoking and second-hand smoke among pregnant Taiwanese women using a questionnaire. Seven hundred twenty-four pregnant Taiwanese women were recruited from an online parenting community using convenience sampling in 2013. Pregnant smokers and non-smokers had significantly different perceptions regarding risk of smoking and second-hand smoke during pregnancy. Pregnant non-smokers adopted more behaviors to avoid second-hand smoke both at home and in public than pregnant smokers. We conclude that perceived fetal health risks from smoking and second-hand smoke influenced maternal behavior during pregnancy. Pregnant women's perceptions of the risk of tobacco smoke depended on whether their focus in the decision-making process was on prevention or promotion. Understanding the risk factors associated with smoking and exposure to second-hand smoke during pregnancy may help in developing strategies to reduce such exposure.

Objective: To investigate the protective effect of paeoniflorin on hippocampal neurons in rats subjected to cerebral ischemia and reperfusion through activating cannabinoid receptor 2 (CBR2)., Methods: A total of 144 male SD rats were randomly divided into sham-operation group, cerebral ischemia-reperfusion model group, menstruum group, 10 and 40 mg/kg paeoniflorin groups, 3 mg/kg CBR2 selective antagonist AM630 group, 40 mg/kg paeoniflorin combined with 3 mg/kg AM630 group, and 3 mg/kg CBR2 selective agonist HU308 treatment group. Focal cerebral ischemia-reperfusion models were made by inserting a monofilament suture into internal carotid artery. The neurological scores, infarction volume and cerebral edema were detected carefully to find out the effect of paeoniflorin on neurons. Pathological changes were observed by HE staining. The expressions of caspase-3 and cyclooxygenase 2 (COX-2) in hippocampal CA1 region were determined by immunohistochemistry., Results: Paeoniflorin significantly decreased the neurological scores, infarction volume and cerebral edema. In addition, paeoniflorin relieved the pathological changes and inhibited the expressions of caspase-3 and COX-2 in hippocampus CA1 area. But injecting AM630 in advance obviously counteracted the neuroprotective effect of paeoniflorin., Conclusion: CBR2 may participate in the protective effect of paeoniflorin on hippocampal neurons of cerebral ischemia-reperfusion rat models.