[Advances in ectoine biosynthesis and biochemical characteristics of key enzymes].

Compatible solutes are highly water-soluble organic osmolytes produced by microorganisms to adapt to extreme environments, such as high salinity and osmotic pressure. Among these, ectoine plays a crucial role in repairing and protecting nucleic acids, protein, biofilms, and cells. As a result, it has found widespread applications in cosmetics, biological agents, the enzyme industry, medicine, and other fields. Currently, the market value of ectoine is around US$ 1 000/kg, with a global demand reaching 15 000 tons per year. Although halophilic bacteria serve as the natural source of ectoine synthesis, its production in high-salinity media presents challenges such as equipment corrosion and high cost for industrial production. Advancements in functional genomics, systems biology, and synthetic biology have paved the way for the development of high-yielding cell factories through metabolic engineering, leading to significant progress. For example, engineered Escherichia coli achieved a maximum ectoine titer of 131.8 g/L, with a productivity of 1.37 g/(L·h). This review aims to explore the biosynthetic pathway, biochemical characteristics of key enzymes, and the biosynthesis of ectoine, shedding light on current research status and offering insights for industrial-scale ectoine production.

Potential benefits of public-private partnerships to improve the efficiency of urban wastewater treatment.

For emerging economies lacking public budgets, continuous improvement of urban wastewater treatment efficiency (UWTE) requires effective government supervision of wastewater treatment infrastructures (WTIs) and participation of private capital seeking to profit-maximising. However, to what extent this public-private partnership (PPP) model, aimed at a reasonable sharing of benefit and risk, in delivering WTIs can improve the UWTE is unknown. We evaluated the impact of the PPP model on the UWTE by collecting data from 1303 urban wastewater treatment PPP projects in 283 prefecture-level cities in China from 2014 to 2019 and used data envelopment analysis and Tobit regression model. The UWTE was significantly higher in prefecture-level cities that introduced the PPP model in the construction and operation of WTIs, particularly those with a feasibility gap subsidy, competitive procurement, privatised operation, and non-demonstration. Moreover, the effects of PPPs on UWTE were limited by the economic development level, marketisation, and climatic conditions.

Hesperetin attenuated acetaminophen-induced hepatotoxicity by inhibiting hepatocyte necrosis and apoptosis, oxidative stress and inflammatory response via upregulation of heme oxygenase-1 expression.

Acetaminophen (APAP) is a common antipyretic and analgesic drug, but its overdose can induce acute liver failure with lack of effective therapies. Hesperetin, a dihydrogen flavonoid compound, has been revealed to exert multiple pharmacological activities. Here, we explored the protective effects and mechanism of hesperetin on APAP-induced hepatotoxicity. The results showed that pretreatment with hesperetin dose-dependently attenuated APAP-induced acute liver injury in mice, as measured by alleviated serum enzymes activities, hepatic pathological damage and apoptosis. Moreover, hesperetin mitigated APAP-induced oxidative stress and inflammatory response in mice by inhibiting oxidative molecules but increasing antioxidative molecules production, reducing inflammatory cells infiltration and proinflammatory cytokines production, blocking Toll-like receptor (TLR)-4 signal activation. In vitro experiment indicated that hesperetin dose-dependently inhibited APAP-primed cytotoxicity, apoptosis, and reactive oxygen species (ROS) in murine AML12 hepatocytes. Notably, hesperetin up-regulated expression of heme oxygenase-1 (HO-1) mRNA and protein in the liver of mice and AML12 cells exposed to APAP. Furthermore, knockdown of HO-1 by adenovirus-mediated HO-1 siRNA reverted these beneficial effects of hesperetin on APAP-induced hepatocytotoxicity as well as ROS and inflammatory response in vivo and in vitro. These findings demonstrated that hesperetin exerted a protective prophylaxis on APAP-induced acute liver injury by inhibiting hepatocyte necrosis and apoptosis, oxidative stress and inflammatory response via up-regulating HO-1 expression.

Photocatalytic acylarylation of unactivated alkenes with diaryliodonium salts toward indanones and related compounds.

A novel photocatalytic acylarylation of unactivated alkenes using diaryliodonium salts as the arylation reagent is described. The reaction produces a variety of 2-benzyl indanones, 3,4-dihydronaphthalen-1(2H)-ones, and 2,3-dihydroquinolin-4(1H)-ones in promising yields with excellent diastereoselectivity under very mild conditions, which may be appealing for the synthesis of biologically active molecules.

Progesterone attenuates hypertension and autoantibody levels to the angiotensin II type 1 receptor in response to elevated cadmium during pregnancy.

INTRODUCTION: Preeclampsia is associated with the presence of pathogenic angiotensin-receptor-activating autoantibodies. Cadmium is an increasingly prevalent environmental pollutant that can mimic oestrogens, which may enhance immunoglobulin production. Progesterone exerts opposite effects to oestrogen. METHODS: We measured the levels of cadmium and progesterone in preeclamptic patients and controls. Pregnant rats exposed to cadmium (0.125 mg/kg body weight) from gestational day 9-12 were treated with/without progesterone (3 mg/kg) beginning from gestational day 9 to delivery. We analysed the main features of preeclampsia and circulating level of the angiotensin II type 1 receptor agonistic autoantibody. We also measured the expression of activation-induced cytosine deaminase in B cells. RESULTS: There were higher cadmium levels and lower progesterone levels in the blood of preeclamptic women than in the blood of those with a healthy pregnancy. Based on this finding, a rat model of preeclampsia was established by intraperitoneally administrating low-dose cadmium on gestational days 9-12. Rats were then treated with/without progesterone. Key features of preeclampsia, including hypertension, proteinuria and placental abnormalities, appeared in pregnant rats after cadmium injection and improved after treatment with progesterone. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies, by increasing the expression of activation-induced cytosine deaminase in B cells; progesterone exerted an opposite effect. CONCLUSION: Cadmium induced immune abnormalities that may be a key pathogenic contributor to preeclampsia. Progesterone supplementation to correct hormonal imbalance may be a viable strategy for preeclampsia management.

Palladium-Catalyzed Site-Selective sp3 C-H Bond Thiocyanation of 2-Aminofurans.

Alkyl thiocyanates are prevalent in natural products, drugs, and biologically active compounds. We report here a novel, mild, and efficient Pd-catalyzed site-selective sp3 C-H bond thiocyanation of 2-aminofurans. Using Na2S2O8 as the oxidant and readily available NaSCN as the thiocyanation reagent, the kinetically favorable 2-amino-4-thiocyanatomethylfurans are selectively synthesized in promising yields with a broad substrate scope. This reaction represents the first example of transition-metal-catalyzed site-selective sp3 C-H bond thiocyanation, thus offering a novel strategy for the step- and atom-economic synthesis of alkyl thiocyanates.

Palladium-catalyzed tandem cyclization/sulfonylation of homoallenyl amides with sodium sulfinates.

A palladium-catalyzed cyclizative sulfonylation of homoallenyl amides using sodium sulfinates as the sulfonylation reagent and PhI(O2CCF3)2 as the oxidant has been realized. The reaction proceeds at room temperature and produces structurally diverse 2-amino-5-sulfonylmethylfurans in good to excellent yields. A Pd(ii)/Pd(iv) catalytic cycle has been proposed for the formation of sulfonylated furans. The concurrent formation of a furan moiety and a C(sp3)-sulfur bond in a single operation makes it a very attractive method for organic synthesis.

An improved Asay window technique for investigating the micro-spall of an explosively-driven tin.

An improved Asay window technique is employed to experimentally investigate the micro-spalling fragments of a melted tin subjected to high explosive loading. Compared to the traditional Asay window, details of the new design are illustrated, through the use of photonic Doppler velocimetry to record high-quality micro-spall signals. The analytical method is established to convert the measured data into the spatial volume density distribution, being in quantitative agreement with that obtained from the x-ray radiograph. This improved non-radiographic technique greatly promotes a wide application in diagnosing the micro-spall.

Lipoxin A4 protects against lipopolysaccharide-induced sepsis by promoting innate response activator B cells generation.

Sepsis is a serious disease that leads to severe inflammation, dysregulation of immune system, multi-organ failure and death. Innate response activator (IRA) B cells, which produce granulocyte-macrophage colony-stimulating factor (GM-CSF), protect against microbial sepsis. Lipid mediator lipoxin A4 (LXA4) exerts anti-inflammatory and immunoregulatory effects, and it has been reported that LXA4 receptor ALX/FPR2 is expressed on B cells. Here, we investigated the potential role of LXA4 on IRA B cells in lipopolysaccharide (LPS)-induced sepsis. We found that LXA4 significantly promoted the expansion of splenic IRA B cells and increased GM-CSF expression in splenic B cells with LPS stimulation. After splenectomy, LXA4 treatment did not change the serum or peritoneal IL-1ß, IL-6 and TNF-α levels in LPS-induced sepsis. LXA4 accelerated the migration of peritoneal B cells to spleen for their differentiation into IRA B cells, whereas this effect was independent of peritoneal macrophage. Furthermore, LXA4 enhanced the phosphorylation level of signal transducer and activator of transcription 5 (STAT5) in splenic B cells. These results suggest that LXA4 protects against LPS-induced sepsis by promoting the generation and migration of splenic IRA B cells, and the underlying molecular mechanism may be related to STAT5 activation. It might provide new insights and therapeutic approaches for treating sepsis.

Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia.

With increased industrial development, cadmium is an increasingly important environmental pollutant. Studies have identified various adverse effects of cadmium on human beings. However, the relationships between cadmium pollution and the pathogenesis of preeclampsia remain elusive. The objective of this study is to explore the effects of cadmium on immune system among preeclamptic patients and rats. The results showed that the cadmium levels in the peripheral blood of preeclamptic patients were significantly higher than those observed in normal pregnancy. Based on it, a novel rat model of preeclampsia was established by the intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg body weight) on gestational days 9-14. Key features of preeclampsia, including hypertension, proteinuria, placental abnormalities and small foetal size, appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies (AT1-AA), by increasing the expression of activation-induced cytosine deaminase (AID) in B cells. AID is critical for the maturation of antibody and autoantibody responses. In addition, angiotensin II type 1-receptor-agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, was responsible for the deposition of complement component 5 (C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R) activation. C5a is a fragment of C5 that is released during C5 activation. Selectively interfering with C5a signalling by a complement C5a receptor-specific antagonist significantly attenuated hypertension and proteinuria in Cd-injected pregnant rats. Our results suggest that cadmium induces immune abnormalities that may be a key pathogenic contributor to preeclampsia and provide new insights into treatment strategies of preeclampsia.

Biotransformation of Resveratrol: New Prenylated trans-Resveratrol Synthesized by Aspergillus sp. SCSIOW2.

Arahypin-16 (1), a new prenylated resveratrol with a unique dihydrobenzofuran ring, has been isolated as a microbial metabolite of resveratrol (2) from whole-cell fermentation of Aspergillus sp. SCSIOW2. The stereochemistry of 1 was determined by ECD calculations. 1 showed about half of the extracellular radical scavenging effect (IC50 = 161.4 µM) compared with resveratrol (IC50 = 80.5 µM), while on biomembranes it exhibited the same range of protection effects against free radicals generated from AAPH (IC50 = 78.6 µM and 87.9 µM).

Numerical determination of non-Langmuirian adsorption isotherms of ibuprofen enantiomers on Chiralcel OD column using ultraviolet-circular dichroism dual detector.

Competitive adsorption isotherm of ibuprofen enantiomers on Chiralcel OD stationary phase at 298K was determined by the application of inverse method. Transport dispersive (TD) chromatography model was used to describe mass balances of the enatiomers. Axial dispersion and mass transfer coefficients were estimated from a series of linear pulse experiments. It was found that the overloaded elution profile of total concentration of racemic ibuprofen cannot be satisfactorily fitted by substituting bi-Langmuir model, the most widely used isotherm model for enantiomers, into TD model and tuning the isotherm parameters. UV-CD dual detector setup was then applied to obtain the individual overloaded elution profiles of both enantiomers. The more informative experimental data revealed non-Langmuirian adsorption behavior of ibuprofen enantiomers on chiralcel OD stationary phase. Two analytical binary isotherm models, both accounting for adsorbate-adsorbate interactions and having the feature of inflection points, were then evaluated. A comparison between quadratic model and Moreau model showed that the former gives better fitting results. The six parameters involved in quadratic model were determined stepwisely. Three of them were first obtained by fitting overloaded elution profiles of S-ibuprofen. The other three were then acquired by fitting overloaded elution profiles of both enantiomers recorded by UV-CD dual detector for racemic ibuprofen. A further attempt was also made at reducing the number of quadratic model parameters.

Competitive adsorption equilibrium model with continuous temperature dependent parameters for naringenin enantiomers on Chiralpak AD column.

Determination of competitive adsorption equilibrium model with continuous temperature dependent parameters is important for the design and optimization of a chromatographic separation process operated under non-isothermal conditions. In this study, linear pulse experiments were first carried to determine the parameters of transport-dispersive model and their temperature dependences in the range of 283­313 K. Overloaded band profiles of naringenin enantiomers on a Chiralpak AD column were acquired under various temperatures. Three of them were first separately fitted using Langmuir, linear-Langmuir and bi-Langmuir isotherm models substituted into the transport-dispersive column model. The comparison showed that bi-Langmuir model captures more details of the experimental results. This model was then extended with three extra parameters accounting for adsorption heat effects and used to simultaneously fit the band profiles at three temperatures.

Four-year follow-up of corneal aberrations and visual functions of myopic patients after laser in situ keratomileusis.

OBJECTIVE: To report on 4-year follow-up of corneal higher-order aberrations and daily visual functions of myopic patients after laser in situ keratomileusis (LASIK). METHODS: One hundred thirty four eyes of 67 patients who underwent LASIK guided by aspherical ablation were included in this study. The vision, corneal spherical aberration (SphA) and Coma were recorded before LASIK and at 6 month and 4 year after LASIK. The evaluation of the questionnaire about daily visual functions was performed by the same physician after LASIK. RESULTS: No eye decreased the BCVA during 4 year follow-up. The effect index and safety index were 1.08±0.16, 1.11±0.17 and 1.12±0.16, 1.13±0.14 respectively at 6 month and 4 year post-LASIK. After LASIK the corneal SphA and Coma were significantly increased, however the difference between 6 month and 4 year post-LASIK was no statistical significance. Most patients (94.3%-92.4%) felt satisfaction or high satisfaction about the ability to perform each daily visual function after LASIK. Meanwhile there was still about 7.4%-9.2% patients who complained that they could not drive at night. Further analysis showed that the score of driving at night was negative correlation with corneal SphA (r=-0.645, p=0.040; r=-0.688, p=0.040 at 6 month and 4 year post-LASIK respectively). CONCLUSIONS: Our four-year follow-up outcomes indicated that the myopic patients after LASIK had the long-term stable corneal aberration and satisfaction of daily visual functions.

Autoimmune pancreatitis characterized by predominant CD8+ T lymphocyte infiltration.

Autoimmune pancreatitis (AIP) is a rare form of pancreatitis characterized by prominent lymphocyte infiltration and pancreatic fibrosis resulting in organ dysfunction. The pathogenesis and pathology of AIP remain unknown. A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas, elevated IgG levels, and negative autoimmune antibody responses. A pylorus-preserving pancreatoduodenectomy was performed and a pancreatic tumor was suspected. However, periductal lymphoplasmacytic infiltration and fibrosis were found in the head of pancreas and nearby organs instead of tumor cells. Four months after surgery, the patient was readmitted because of reoccurrence of severe jaundice and sustained abdominal distension. Prednisone 30 mg/d was administered orally as an AIP was suspected. One and a half months later, the symptoms of the patient disappeared, and globulin, aminotransferase and bilirubin levels decreased significantly. Over a 9-mo follow-up period, the dose of prednisone was gradually decreased to 10 mg/d and the patient remained in good condition. We further demonstrated dominant CD3+/CD8+ populations, CD20+ cells and a few CD4+ cells in the pancreatic parenchyma, duodenum and gallbladder wall by immunohistochemical assay. This AIP case presented with significant CD8+ T lymphocyte infiltration in the pancreas and extra-pancreatic lesions, indicating that this cell population may be more important in mediating AIP pathogenesis than previously known and that AIP might be a poorly defined autoimmune disease with heterogeneous pathogenesis.

Diffuse lupus encephalopathy in a case of rhupus syndrome.

"Rhupus syndrome" is a rare clinical condition, which is related to anti-CCP antibody, characterized by overlapping clinical and immunologic features of rheumatoid arthritis and systemic lupus erythematosus. Previous reports mentioned that patients have more RA-associated damage, and little organic damage associated with SLE. The severe organ damage, especially central nervous system involvement has been reported to be rare in patients with rhupus syndrome. Here, we report a very rare concurrence of RA, SLE and diffuse lupus encephalopathy in a Chinese woman.

[Clinical efficacy of Corydalis composite combined with methotrexate in treating rheumatoid arthritis].

OBJECTIVE: To observe the clinical efficacy and safety of Corydalis composite (CDC) combined with methotrexate (MTX) in treating rheumatoid arthritis (RA). METHODS: Seventy-six RA patients were randomly assigned to 2 groups, 37 in the treated group received the combined therapy, and the 39 received MTX treatment alone, all were treated for 12 weeks. Efficacy of treatment was evaluated adopting the standard of American College of Rheumatology (ACR), taking ACR20 as the chief criterion; ACR50, ACR70 as well as the clinical indexes and items in Health Account Questionnaire (HAQ) as the auxiliary criteria, including joint swelling index, joint tenderness index, holding power, morning stiffness time, resting pain, erythrocyte sedimentation rate (ESR), C-reactive protein. And the adverse reaction was recorded at the same time. RESULTS: After being treated for 4, 8 and 12 weeks, the ACR20 response rate reached 35.14%, 59.46% and 70.27% respectively in patients of the treated group, while that in the control group was 17.95%, 35.90% and 46.15% respectively, significant difference between groups was shown in the outcome of week 8 and 12 (P < 0.05). ACR50 and ACR70 improving rate at all the time points of observation were increased in the treated group, with the ACR50 improving rate at week 12 higher than that in the control group (43.24% vs. 20.51%, P < 0.05). As compared with the control group, the improvements in all the auxiliary criteria were more significant in the treated group (P < 0.05). The incidence of adverse reaction was less in the treated group than in the control group (32.43% vs. 56.41%, P < 0.05), particularly in term of the damage on liver (0 vs. 10.26%, P < 0.05). CONCLUSION: CDC combined with MTX is more effective than MTX alone in treating active RA with less adverse reaction.

Sequential activation of protein kinase C delta and JNK is required for interferon-alpha-induced expression of IFIT4.

A multitude of interferon (IFN)-inducible genes (IFIGs) are coordinately expressed in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), emphasising the globle activating of signal pathway mediated by IFN-I in SLE. In this study, we investigated the mechanisms of expression regulation of IFIT4 (interferon induced protein with tetratricopeptide repeats 4) by IFN-alpha. We found that IFN-alpha failed in inducing IFIT4 in STAT1-negative U3A cells. Ectopic expression of STAT1, but not mutant STAT1-S727A, almost completely restored IFN-alpha2a-induced IFIT4 expression. IFN-alpha induced the expression of IFIT4 and STAT1 in THP-1 cells, and this process was significantly antagonized by the specific inhibitors of both PKCdelta and JNK or their dominant negative mutants respectively. The inhibition of JNK activity by its specific inhibitor or its dominant negative mutant suppressed both IFIT4 expression and serine phosphorylation of STAT1 but not the activation of PKCdelta, while inhibition of PKCdelta suppressed activation of IFIT4, STAT1, and JNK. Our results suggest that the induction of IFIT4 transcription by IFN-alpha depends upon sequential activation of PKCdelta, JNK and STAT1, and that the influence of PKCdelta or JNK on IFN-alpha-mediated induction of IFIT4 is dependent upon the phosphorylation of STAT1 at Ser-727. The results in our experiment provide an in vitro model of the signaling mechanisms of IFIGs regulated by IFN-alpha, that is putatively thought to occur in vivo as the one of pathogenesis of SLE.