Candesartan upregulates angiotensin-converting enzyme 2 in kidneys of male animals by decreased ubiquitination.

Candesartan is a common angiotensin-II receptor-1 blocker used for patients with cardiovascular and renal diseases. Angiotensin-converting enzyme 2 (ACE2) is a negative regulator of blood pressure (BP), and also a major receptor for coronaviruses. To determine whether and how candesartan upregulates ACE2, we examined BP and ACE2 in multi-organs from male and female C57BL/6J mice treated with candesartan (1 mg/kg, i.p.) for 7 days. Relative to the vehicle, candesartan lowered BP more in males than females; ACE2 protein abundances were increased in kidneys, not lungs, hearts, aorta, liver, spleen, brain, or serum, only from males. Ace2-mRNA was similar in kidneys. Candesartan also decreased BP in normal, hypertensive, and nephrotic male rats. The renal ACE2 was increased by the drug in normal and nephrotic male rats but not spontaneously hypertensive ones. In male mouse kidneys, ACE2 was distributed at sodium-hydrogen-exchanger-3 positive proximal-convoluted-tubules; ACE2-ubiquitination was decreased by candesartan, accompanied with increased ubiquitin-specific-protease-48 (USP48). In candesartan-treated mouse renal proximal-convoluted-tubule cells, ACE2 abundances and activities were increased while ACE2-ubiquitination and colocalization with lysosomal and proteosomal markers were decreased. The silence of USP48 by siRNA caused a reduction of ACE2 in the cells. Thus, the sex-differential ACE2 upregulation by candesartan in kidney from males may be due to the decreased ACE2-ubiquitination, associated with USP48, and consequent degradation in lysosomes and proteosomes. This is a novel mechanism and may shed light on candesartan-like-drug choice in men and women prone to coronavirus infections.

Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia.

The kidney regulates blood pressure through salt/water reabsorption affected by tubular sodium transporters. Expanding our prior research on placental cluster of differentiation 81 (CD81), this study explores the interaction of renal CD81 with sodium transporters in preeclampsia (PE). Effects of renal CD81 with sodium transporters were determined in lipopolysaccharide (LPS)-induced PE rats and immortalized mouse renal distal convoluted tubule cells. Urinary exosomal CD81, sodium potassium 2 chloride cotransporter (NKCC2), and sodium chloride cotransporter (NCC) were measured in PE patients. LPS-PE rats had hypertension from gestational days (GD) 6 to 18 and proteinuria from GD9 to GD18. Urinary CD81 in both groups tented to rise during pregnancy. Renal CD81, not sodium transporters, was higher in LPS-PE than controls on GD14. On GD18, LPS-PE rats exhibited higher CD81 in kidneys and urine exosomes, higher renal total and phosphorylated renal NKCC2 and NCC with elevated mRNAs, and lower ubiquitinated NCC than controls. CD81 was co-immunoprecipitated with NKCC2 or NCC in kidney homogenates and co-immunostained with NKCC2 or NCC in apical membranes of renal tubules. In plasma membrane fractions, LPS-PE rats had greater amounts of CD81, NKCC2, and NCC than controls with enhanced co-immunoprecipitations of CD81 with NKCC2 or NCC. In renal distal convoluted tubule cells, silencing CD81 with siRNA inhibited NCC and prevented LPS-induced NCC elevation. Further, PE patients had higher CD81 in original urines, urine exosomes and higher NKCC2 and NCC in urine exosomes than controls. Thus, the upregulation of renal CD81 on NKCC2 and NCC may contribute to the sustained hypertension observed in LPS-PE model. Urine CD81 with NKCC2 and NCC may be used as biomarkers for PE.

Itaconate inhibits SYK through alkylation and suppresses inflammation against hvKP induced intestinal dysbiosis.

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.

Synergistic effects of silicon and goethite co-application in alleviating cadmium stress in rice (Oryza sativa L.): Insights into plant growth and iron plaque formation mechanisms.

Rice is one of the most important staple food crops; however, it is prone to cadmium (Cd) accumulation, which has negative health effects. Therefore, methods to reduce Cd uptake by rice are necessary. At present, there is limited research on the effects of co-application of silicon (Si) and goethite in mitigating Cd stress in rice. Furthermore, the specific mechanisms underlying the effects of their combined application on iron plaque formation in rice roots remain unclear. Therefore, this study analyzed the effects of the combined application of Si and goethite on the biomass, physiological stress indicators, Cd concentration, and iron plaques of rice using hydroponic experiments. The results revealed that co-treatment with both Si and goethite increased the plant height and dry weight, superoxide dismutase and catalase activities, photosynthetic pigment concentration, and root activity. Moreover, this treatment decreased the malondialdehyde concentration, repaired epidermal cells, reduced the Cd concentration in the roots by 57.2 %, and increased the number of iron plaques and Cd concentration by 150.9 % and 266.2 % in the amorphous and crystalline fractions, respectively. The Cd/Fe ratio in amorphous iron plaques also increased. Our findings suggest that goethite serves as a raw material for iron plaque formation, while Si enhances the oxidation capacity of rice roots. The application of a combination of Si and goethite increases the quantity and quality of iron plaques, enhancing its Cd fixation capacity. This study provides theoretical evidence for the effective inhibition of Cd uptake by iron plaques in rice, providing insights into methods for the remediation of Cd contamination.

Source depth estimation with feature matching using convolutional neural networks in shallow water.

A feature matching method based on the convolutional neural network (named FM-CNN), inspired from matched-field processing (MFP), is proposed to estimate source depth in shallow water. The FM-CNN, trained on the acoustic field replicas of a single source generated by an acoustic propagation model in a range-independent environment, is used to estimate single and multiple source depths in range-independent and mildly range-dependent environments. The performance of the FM-CNN is compared to the conventional MFP method. Sensitivity analysis for the two methods is performed to study the impact of different environmental mismatches (i.e., bottom parameters, water column sound speed profile, and topography) on depth estimation performance in the East China Sea environment. Simulation results demonstrate that the FM-CNN is more robust to the environmental mismatch in both single and multiple source depth estimation than the conventional MFP. The proposed FM-CNN is validated by real data collected from four tracks in the East China Sea experiment. Experimental results demonstrate that the FM-CNN is capable of reliably estimating single and multiple source depths in complex environments, while MFP has a large failure probability due to the presence of strong sidelobes and wide mainlobes.

Cadmium distribution and transformation in leaf cells involved in detoxification and tolerance in barley.

Barley is a diagnostic plant that often used in the research of soil pollution by heavy metals, our research explored the detoxification and tolerance mechanism of cadmium(Cd) in barley through pot experiment. We investigated subcellular distribution, chemical forms and oxidative damage of Cd in barley leaves, combing with the transmission electron microscopy and Fourier-transform infrared spectroscopy(FT-IR) to further understand the translocation, transformation characteristics and toxic effect of Cd in cells. The results showed that, the bioaccumulation factors in roots and shoots of barley were ranged of 4.03-7.48 and 0.51-1.30, respectively. Barley reduces the toxic effects by storing Cd in the roots and reducing its transport to the shoots. Compared to the control treatment (0 mg/kg), the percentage of Cd in the cell wall fractions of leaves in 300 mg/kg Cd treatment increased from 34.74 % to 38.41 %; the percentage of the organelle fractions increased from 24.47 % to 56.02 %; and the percentage of soluble fraction decreased from 40.80 % to 5.57 %. We found that 69.13 % of the highly toxic inorganic Cd and water-soluble Cd were converted to less toxic pectates and protein-integrated Cd (50.20 %) and undissolved Cd phosphates (18.93 %). This conversion of Cd was mainly due to its combination with -OH, -NH, -CN, -C-O-C, and -C-O-P groups. Excessive Cd induced a significant (P < 0.05) increase in the levels of peroxidase, malondialdehyde, and cell membrane permeability, which damaged the cell membrane and allowed Cd to enter the organelles. The chloroplasts and mitochondria were destroyed, and eventually the metabolism of intracellular substances was affected, resulting in symptoms of toxicity. Our research provides cellular-scale insight into the mechanisms of Cd tolerance in barley.

Deep-learning geoacoustic inversion using multi-range vertical array data in shallow water.

A multi-range vertical array data processing (MRP) method based on a convolutional neural network (CNN) is proposed to estimate geoacoustic parameters in shallow water. The network input is the normalized sample covariance matrices of the broadband multi-range data received by a vertical line array. Since the geoacoustic parameters (e.g., bottom sound speed, density, and attenuation) have different scales, the multi-task learning is used to estimate these parameters simultaneously. To reduce the influence of the uncertainty of the source position, the training and validation data are composed of the simulation data of different source depths. Simulation results demonstrate that compared with the conventional matched-field inversion (MFI), the CNN with MRP alleviates the coupling between the geoacoustic parameters and is more robust to different source depths in the shallow water environment. Based on the inversion results, better localization performance is achieved when the range-dependent environment is assumed to be a range-independent model. Real data from the East China Sea experiment are used to validate the MRP method. The results show that, compared with the MFI and the CNN with single-range vertical array data processing, the use of geoacoustic parameters from MRP achieves better localization performance.

Effects of Silicon and Iron Application on Arsenic Absorption and Physiological Characteristics of Rice (Oryza sativa L.).

This study investigated the effects of silicon and iron on arsenic absorption, as well as the changes in the physiological indices of rice under arsenic stress and how these indices respond to silicon and iron. We found that application of silicon and iron reduces arsenic absorption in rice; co-application of silicon and iron reduced arsenic content by 25.6%-27.4%. The antioxidant enzyme activities of rice treated with silicon and iron were significantly lower than those of untreated rice, with the biggest decreases observed under co-application treatments. Iron significantly increased osmoregulatory substances, while silicon increased soluble sugar; Si1Fe1 treatment (containing 1 mM silicon, 0.1 mM iron) had the highest content of osmoregulatory substances except CK. Membership function analysis suggested that applying silicon and iron alone alleviates the stress condition in rice, with the lowest stresses observed under Si1Fe1 treatment. These results show that silicon and iron co-application significantly inhibits arsenic uptake in rice, decreases the antioxidant enzymes activity, while non-enzymatic substances in rice can be regulated to further alleviate arsenic stress.

A Fluorescent Zn(II)-Coordination Polymer: Selective Detection of Nitrofurantoin and Prevention of Peri-Implantitis after Ultrafine-Grained Titanium Implant by Reducing Inflammatory Cytokines Release.

In the current research, a novel coordination polymer (CP) containing Zn(II) ions as nodes with the chemical formula of [Zn(IPT)2]n (1) has been produced via reaction of Zn(NO3)2·6H2O with 5-(3-(1H-imidazol-1-yl)phenyl)-1H-tetrazolate (HIPT), a heterotopic imidazole-tetrazole-bifunctional ligand. The as-prepared complex 1 has been charactered via single crystal X-ray diffraction, elemental analysis, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA) and fourier transform infrared spectroscopy (FT-IR). Because of its outstanding luminescent performances and stability, the synthesized complex 1 is a kind of excellent material of luminescent sensor of nitrofurantoin (NFT) in the water. The value of Ksv for the complex 1 to NFT is about 1.4 × 104 M-1. For the treatment of the peri-implantitis with complex 1, the ELISA test was carried out to determine the levels of the inflammatory cytokines released into the gingival crevicular fluid. The results showed that the levels of the inflammatory cytokines could be significantly reduced by complex 1 treatment. In addition to this, the real time RT-PCR was also conducted, and the data suggested the signaling pathway of TLR-4-NF-κB activation was inhibited by complex 1.

Sulforaphane Protect Against Cadmium-Induced Oxidative Damage in mouse Leydigs Cells by Activating Nrf2/ARE Signaling Pathway.

Cadmium (Cd) is harmful for humans and animals, especially for the reproductive system. However, the mechanism of its toxicity has not been elucidated, and how to alleviate its toxicity is very important. This study aimed to explore the role and mechanism of action of sulforaphane (SFN) in protecting mouse Leydigs (TM3) cells from cadmium (Cd)-induced damage. The half-maximal inhibitory concentration (IC50) of Cd and the safe doses of SFN were determined using a methyl thiazolyl tetrazolium (MTT) assay. The testosterone secretion from TM3 cells was measured using the enzyme-linked immunosorbent assay. The intracellular oxidative stress was evaluated using corresponding kits. The cell apoptosis was detected using flow cytometry. The mRNA expression of genes associated with NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling was detected using reverse transcription⁻polymerase chain reaction, including Nrf2, heme oxygenase I (HO-1), glutathione peroxidase (GSH-Px), NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase (γ-GCS). The protein expression of Nrf2, GSH-Px, HO-1, γ-GCS, and NQO1 was detected using Western blot analysis. The results showed that the IC50 of Cd to TM3 cells was 51.4 µmol/L. SFN reduced the release of lactate dehydrogenase from Cd-exposed cells. Cd + SFN 2.5 treatment significantly elevated testosterone concentration compared with the Cd group (p < 0.05). SFN significantly increased total superoxide dismutase (T-SOD) and GSH-Px activity and GSH content in Cd-treated cells (p < 0.05; p < 0.01), inhibited the production of malondialdehyde or reactive oxygen species caused by Cd (p < 0.05; p < 0.01), and reduced the apoptotic rate of Cd-induced TM3 cells (p < 0.01). SFN upregulated the mRNA expression of Nrf2, GSH-Px, HO-1, NQO1, and γ-GCS in Cd-treated cells, indicating the protective effect of SFN against Cd-induced oxidative stress or cell apoptosis by activating the Nrf2/ARE signaling pathway.

Sulforaphane Prevents Testicular Damage in Kunming Mice Exposed to Cadmium via Activation of Nrf2/ARE Signaling Pathways.

Sulforaphane (SFN) is a natural and highly effective antioxidant. Studies suggest that SFN protects cells and tissues against cadmium (Cd) toxicity. This study investigated the protective effect of SFN against oxidative damage in the testes of Kunming mice exposed to cadmium, and explored the possible molecular mechanisms involved. Cadmium greatly reduced the serum testosterone levels in mice, reduced sperm motility, total sperm count, and increased the sperm deformity rate. Cadmium also reduces superoxide dismutase (T-SOD) and glutathione (GSH) levels and increases malondialdehyde (MDA) concentrations. SFN intervention improved sperm quality, serum testosterone, and antioxidant levels. Both mRNA and protein expression of mouse testicular nuclear factor-erythroid 2-related factor 2 (Nrf2) was reduced in cadmium-treated group. Furthermore, the downstream genes of Nrf2, glutathione peroxidase (GSH-Px), γ-glutamyl cysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO1) were also decreased in cadmium-treated group. SFN intervention increases the expression of these genes. Sulforaphane prevents cadmium-induced testicular damage, probably via activation of Nrf2/ARE signaling.

Meta-analysis of the curative effect of sacral nerve magnetic stimulation on neurogenic bladder after spinal cord injury.

BACKGROUND: The curative effect of sacral nerve magnetic stimulation on the neurogenic bladder (NB) after spinal cord injury (SCI) is unclear. This study made a meta-analysis of the curative effect of sacral nerve magnetic stimulation on the NB after SCI and put forward a theoretical basis for the clinical treatment of this disease. METHODS: The databases of PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP, and CBM were searched by computer, and the randomized controlled trials of sacral nerve magnetic stimulation in the treatment of NB after SCI were collected. The retrieval time was from the establishment of the database to September 25, 2023. Meta-analysis was performed with Stata 15.0 software. RESULTS: This study finally included 10 articles, including 537 patients. Meta-analysis shows that the sacral nerve magnetic stimulation treatment group can effectively improve urodynamics: the maximum bladder capacity increases (mean difference [MD], 40.76 [95% confidence interval (CI), 33.24-48.28]; P ˂ .05), the bladder capacity increases at the beginning of urination (MD, 12.82 [95% CI, 11.02-14.62]; P ˂ .05), and the residual urine volume decreases (MD, -38.08 [95% CI, -51.36 to -24.79]; P˂.05). In the aspect of urination diary, the sacral nerve magnetic stimulation treatment group also has advantages compared with the conventional treatment group: the increase in single urine volume (MD, 22.49 [95% CI, 18.68-26.30]; P˂.05), the maximum urine volume (MD, 32.84 [95% CI, 22.37-43.30]; P˂.05), and the decrease in urination times (MD, -2.23 [95% CI, -3.13 to -1.33]; P˂.05). After the treatment of sacral nerve magnetic stimulation, the quality of life of patients can be improved: quality-of-life score (MD, -0.62 [95% CI, -0.91 to -0.34]; P˂.05). CONCLUSION: Combined with functional magnetic stimulation of the sacral nerve, routine treatment is superior to routine treatment in improving the clinical symptoms of patients with NB after SCI.

The salt sensitivity of Drd4-null mice is associated with the upregulations of sodium transporters in kidneys.

To explore the mechanism of the hypertension in dopamine receptor-4 (Drd4) null mice, we determined the salt sensitivity and renal sodium transport proteins in Drd4-/- and Drd4+/+ mice with varied salt diets. On normal NaCl diet (NS), mean arterial pressures (MAP, telemetry) were higher in Drd4-/- than Drd4+/+; Low NaCl diet (LS) tended to decrease MAP in both strains; high NaCl diet (HS) elevated MAP with sodium excretion decreased and pressure-natriuresis curve shifted to right in Drd4-/- relative to Drd4+/+ mice. Drd4-/- mice exhibited increased renal sodium-hydrogen exchanger 3 (NHE3), sodium-potassium-2-chloride cotransporter (NKCC2), sodium-chloride cotransporter (NCC), and outer medullary α-epithelial sodium channel (αENaC) on NS, decreased NKCC2, NCC, αENaC, and αNa+-K+-ATPase on LS, and increased αENaC on HS. NKCC2, NCC, αENaC, and αNa+-K+-ATPase in plasma membrane were greater in Drd4-/- than in Drd4+/+ mice with HS. D4R was expressed in proximal and distal convoluted tubules, thick ascending limbs, and outer medullary collecting ducts and colocalized with NKCC2 and NCC. The phosphorylation of NKCC2 was enhanced but ubiquitination was reduced in the KO mice. There were no differences between the mouse strains in serum aldosterone concentrations and urinary dopamine excretions despite their changes with diets. The mRNA expressions of renal NHE3, NKCC2, NCC, and αENaC on NS were not altered in Drd4-/- mice. Thus, increased protein expressions of NHE3, NKCC2, NCC and αENaC are associated with hypertension in Drd4-/- mice; increased plasma membrane protein expression of NKCC2, NCC, αENaC, and αNa+-K+-ATPase may mediate the salt sensitivity of Drd4-/- mice.

The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice.

The exact relationship between nicotine metabolism and dependence is not fully understood but is known to be influenced at a molecular level by genetic factors. A sample comprising 274 Chinese adult male smokers was categorized into groups based on their metabolic rates, namely fast, intermediate, and slow metabolizers. We then measured their smoking topography, evaluated their nicotine dependence, and assessed the rewarding effects. Based on these findings, we proposed the hypothesis that the rate of nicotine metabolism could influence the level of dopamine release which in turn had repercussions on the pleasurable and rewarding effects. To test this hypothesis, male mice were selected with different nicotine metabolic rates that closely resembled in the smoker group. We evaluated their nicotine dependence and rewarding effects through conditioned place preference and withdrawal symptom tests, supplemented with dopamine release measurements. In both animal and human, the slow metabolism group (SMG) required less nicotine to maintain a comparable level of dependence than the fast metabolism group (FMG). The SMG could achieve similar rewarding effects to FMG despite consuming less nicotine. Comparable dopamine levels released were therefore critical in setting the nicotine acquisition behavior in this animal model and also for the smokers tested. Our findings suggested that even within the same ethnicity of established smokers (Chinese Han), differences in nicotine metabolism were an important parameter to modulate the degree of nicotine dependence.

DOPAMINE D4 RECEPTOR DOWN-REGULATES RENAL SODIUM CHLORIDE COTRANSPORTER VIA UBIQUITINATION-ASSOCIATED LYSOSOME DEGRADATION.

BACKGROUND: The thiazide-sensitive sodium chloride cotransporter (NCC) is the major apical sodium transporter located in the mammalian renal distal convoluted tubule (DCT). The amount of sodium reabsorbed in the DCT through NCC plays an important role in the regulation of extracellular fluid volume and blood pressure. Dopamine and its receptors constitute a renal antihypertensive system in mammals. The disruption of Drd4 in mice causes kidney-related hypertension. However, the pathogenesis of D4R-deficiency associated hypertension is not well documented. METHOD: We assessed the effects of D4R on NCC protein abundances and activities of DCT in mice with renal or global Drd4-deficiencies and expressing human D4.7 variant and in cultured mouse DCT cells, and explored the molecular mechanism. RESULTS: NCC inhibitor hydrochlorothiazide enhanced the natriuresis in Drd4-/- mice. Renal NCC protein was greater while ubiquitination of NCC was less in Drd4-/- than Drd4+/+ mice. Silencing of D4R in cultured mouse DCT cells increased NCC protein but decreased NCC ubiquitination. D4R agonist had opposite effects that were blocked by the antagonist. In mouse kidneys and DCT cells D4R and NCC colocalized and co-immunoprecipitated. Moreover, D4R-agonist promoted the binding between the two proteins demonstrated by fluorescence resonance energy transfer. D4R agonism internalized NCC, decreased NCC in the plasma membrane, increased NCC in lysosomes and reduced NCC-dependent-intracellular-sodium transport. The lysosomal inhibitor chloroquine prevented the D4R-induced NCC-reduction. A shortened NCC half-life was suggested by its decay under cycloheximide-chase. Ubiquitin-specific-protease 48 (USP48, a deubiquitinating enzyme) was increased in the kidneys and cells with Drd4-deficiency while D4R stimulation decreased it in vitro and reduction of USP48 with siRNA decreased NCC expression. The mice carrying human D4.7 variant or with renal supcapsular-Drd4-siRNA-delivery developed hypertension with increased NCC. CONCLUSION: Our data demonstrates that D4R downregulates NCC by promoting USP48-associated deubiquitination and subsequent internalization, lysosome relocation and degradation.

Treatment of bilateral developmental dysplasia of the hip joint with an improved technique: A case report.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common osteoarticular deformity in pediatric orthopedics. A patient with bilateral DDH was diagnosed and treated using our improved technique "(powerful overturning acetabuloplasty)" combined with femoral rotational shortening osteotomy. CASE SUMMARY: A 4-year-old girl who was diagnosed with bilateral DDH could not stand normally, and sought surgical treatment to solve the problem of double hip extension and standing. As this child had high dislocation of the hip joint and the acetabular index was high, we changed the traditional acetabuloplasty to "powerful turnover acetabuloplasty" combined with femoral rotation shortening osteotomy. During the short-term postoperative follow-up (1, 3, 6, 9, 12, and 15 months), the child had no discomfort in her lower limbs. After the braces and internal fixation plates were removed, formal rehabilitation training was actively carried out. CONCLUSION: Our "powerful overturning acetabuloplasty" combined with femoral rotational shortening osteotomy is feasible in the treatment of DDH in children. This technology may be widely used in the clinic.

FASN regulates STING palmitoylation via malonyl-CoA in macrophages to alleviate sepsis-induced liver injury.

STING (stimulator of interferon genes) is a critical immunoregulatory protein in sepsis and is regulated by various mechanisms, especially palmitoylation. FASN (fatty acid synthase) is the rate-limiting enzyme to generate cellular palmitic acid (PA) via acetyl-CoA and malonyl-CoA and participates in protein palmitoylation. However, the mechanisms underlying the interaction between STING and FASN have not been completely understood. In this study, STING-knockout mice were used to confirm the pivotal role of STING in sepsis-induced liver injury. Metabolomics confirmed the dyslipidemia in septic mice and patients. The compounds library was screened, revealing that FASN inhibitors exerted a significant inhibitory effect on the STING pathway. Mechanically, the regulatory effect of FASN on the STING pathway was dependent on palmitoylation. Further experiments indicated that the upstream of FASN, malonyl-CoA inhibited STING pathway possibly due to C91 (palmitoylated residue) of STING. Overall, this study reveals a novel paradigm of STING regulation and provides a new perspective on immunity and metabolism.

Implementation of Bartlett matched-field processing using interpretable complex convolutional neural network.

Neural networks have been applied to underwater source localization and achieved better performance than the conventional matched-field processing (MFP). However, compared with MFP, the neural networks lack physical interpretability. In this work, an interpretable complex convolutional neural network based on Bartlett processor (BC-CNN) for underwater source localization is designed, the output and structure of which have clear physical meanings. The relationship between the convolution weights of BC-CNN and replica pressure of MFP is discussed, which effectively presents the interpretability of the BC-CNN. Simulation experiments using two kinds of labels demonstrate the equivalence between the Bartlett MFP and BC-CNN.

Effects of blast furnace slag on the immobilization, plant uptake and translocation of Cd in a contaminated paddy soil.

The potential toxicity of Cd to soil and rice plant severely threaten human health. This study was conducted to investigate the remediation effects of blast furnace slag (BFS) on the bioavailability of Cd in a contaminated paddy soil from a perspective of soil solution chemistry. Batch experiments, pot culture experiments, and principal analysis (PCA) were used to study the effects and mechanisms of BFS addition changing Cd chemical behavior and Cd toxicity. Results indicated that BFS facilitated Cd adsorption in soils, increased pH, Eh, and EC values in soil solution, whereas reduced dissolved Cd content. BFS amendment was efficient in decreasing root Cd intake and Cd upward transport in rice plant, with the Cd translocation factor in brown rice decreased by âˆ¼ 75% (BFS treatment, 6‰ wt) relative to Cd treatment, which in turn increased rice biomass and grain yield. PCA indicated that the dissolved Cd concentration had a close relationship with soil pH and metal concentration in soil solution. Results from this study indicated that BFS had potential ability for either immobilization or remobilization of Cd in soils, and the findings have important implications for Cd-polluted soil remediation or other resource utilization with slag-based materials.

Ecosystem service value of conservation tillage with cover crop-maize intercropping in the black soil region of Northeast China.

Scientific evaluating ecosystem service value (ESV) of cover crop cultivation system can provide important guidance for the construction of conservation tillage pattern in Northeast China. Based on empirical analysis and the theory of ecosystem service value, we calculated the ESVs of intercropping maize with gramineous cover crop ryegrass and with leguminous cover crops, alfalfa and hairy vetch, with maize monoculture as the control. The ESVs included product supply, gas regulation, nutrient cycling, and soil and water conservation. Results showed that ESVs of cover crop-maize intercropping were higher than those of maize monoculture. Nutrient cycling value was the highest, followed by product supply value, accounting for 67.3% and 29.3% of total ESV, respectively. The nutrient cycling value of cover crop-maize intercropping was higher than that of maize monoculture. The product supply value of alfalfa-maize and hairy vetch-maize were 18.7% and 21.0% higher than that of ryegrass-maize, respectively. Cover crops had the potential to increase the value of gas regulation services, but had little impact on the value of soil and water conservation. Considering the ESVs, intercropping maize with leguminous cover crops would have the greatest benefits.