Molecular engineering of PETase for efficient PET biodegradation.

The widespread utilization of polyethylene terephthalate (PET) has caused a variety of environmental and health problems. Compared with traditional thermomechanical or chemical PET cycling, the biodegradation of PET may offer a more feasible solution. Though the PETase from Ideonalla sakaiensis (IsPETase) displays interesting PET degrading performance under mild conditions; the relatively low thermal stability of IsPETase limits its practical application. In this study, enzyme-catalysed PET degradation was investigated with the promising IsPETase mutant HotPETase (HP). On this basis, a carbohydrate-binding module from Bacillus anthracis (BaCBM) was fused to the C-terminus of HP to construct the PETase mutant (HLCB) for increased PET degradation. Furthermore, to effectively improve PET accessibility and PET-degrading activity, the truncated outer membrane hybrid protein (FadL) was used to expose PETase and BaCBM on the surface of E. coli (BL21with) to develop regenerable whole-cell biocatalysts (D-HLCB). Results showed that, among the tested small-molecular weight ester compounds (p-nitrophenyl phosphate (pNPP), p-Nitrophenyl acetate (pNPA), 4-Nitrophenyl butyrate (pNPB)), PETase displayed the highest hydrolysing activity against pNPP. HP displayed the highest catalytic activity (1.94 µM(p-NP)/min) at 50 °C and increased longevity at 40 °C. The fused BaCBM could clearly improve the catalytic performance of PETase by increasing the optimal reaction temperature and improving the thermostability. When HLCB was used for PET degradation, the yield of monomeric products (255.7 µM) was ∼25.5 % greater than that obtained after 50 h of HP-catalysed PET degradation. Moreover, the highest yield of monomeric products from the D-HLCB-mediated system reached 1.03 mM. The whole-cell catalyst D-HLCB displayed good reusability and stability and could maintain more than 54.6 % of its initial activity for nine cycles. Finally, molecular docking simulations were utilized to investigate the binding mechanism and the reaction mechanism of HLCB, which may provide theoretical evidence to further increase the PET-degrading activities of PETases through rational design. The proposed strategy and developed variants show potential for achieving complete biodegradation of PET under mild conditions.

Pentanary Oxythiogermanates Ba3MGe3O2S8 (M = Ca, Zn) Featuring [Ge3O2S8]8- Trimers and {[MGe3O2S8]6-}∞ Chains: Structural Chemistry and Physical Properties.

Oxychalcogenides are increasingly attracting wide attention because they contain multiple anions that may combine the advantages of oxides and chalcogenides. In this work, two new pentanary oxythiogermanates, Ba3MGe3O2S8 [M = Ca (1), Zn (2)], were synthesized by a high-temperature solid-state reaction. They crystallize in the orthorhombic space group Pnma, and their structures contain isolated [Ge3O2S8]8- units constructed by one [GeO2S2] and two [GeOS3] tetrahedra that link with M2+ ions to build the {[MGe3O2S8]6-}∞ chain, representing a new type of oxythiogermanate. Notably, a [ZnS5] square pyramid exists in 2. Their structural chemistry and relationship with relevant structures are analyzed. 1 and 2 exhibit wide band gaps of 3.93 and 2.63 eV, birefringences of 0.100 and 0.089 at 2100 nm, respectively, and also obvious photocurrent responses. This work may be extended to a family of AE3MIIMIV3O2Q8 (AE = alkali-earth metal; MII = Ca, Zn, Cd, Hg; MIV = Si, Ge, Sn; Q = S, Se), and further systematic survey on them can be performed to enrich the study of multifunctional oxychalcogenides.

Drug recommendation for optimization on treatment outcome for MDR/RR-TB based on a multi-center, large scale, retrospective cohort study in China.

OBJECTIVE: With the change in drug-resistant pattern, MDR/RR-TB was faced with underlying changes in regimens. A multi-center, large-scale, retrospective study performed aims to provide a recommendation of drug selection on optimization of outcome for the patients. METHOD: The study was conducted in six TB-specialized hospitals in China. Patients were included from 2018-2021 and followed up throughout the treatment. Using a multivarariable and propensity score-matched logistic regression analysis, we evaluated associations between outcomes and drug use, as well as clinical characteritics. RESULTS: Of 3112 patients, 74.29% had treatment sucess, 14.52% lost to follow-up, 9.67% failure, and 1.51% died. Treatment success was positively associated with Bedaquiline(Bdq), Linezolid(Lzd), and Cycloserin(Cs). Capreomycin(Cm) increased the risk of unfavorable outcomes. other drugs such as Amikacin(Amk) and clofazimine had no significant effect on outcomes. If isolates were susceptible to fluoroquinolones(FQs), FQs could decrease the risk of unfavorable outcomes. CONCLUSIONS: The recommendation order for the treatment of MDR/RR-TB is Bdq, Lzd, and Cs. FQs were decreased in use intensity. Injection drugs, whether Amk or Cm, are not recommended.

Effects of the construction of fertile and cultivated soil layer on soil fertility and maize yield in Albic soil.

We examined the effects of fertile soil layer construction technology on soil fertility and maize yield with a 3-year field experiment in Albic soil in Fujin, Heilongjiang Province. There were five treatments, including conventional tillage (T15, without organic matter return) and fertile soil layer construction methods [deep tillage (0-35 cm) with straw return, T35+S; deep tillage with organic manure, T35+M; deep tillage with straw and organic manure return, T35+S+M; deep tillage with straw, organic manure return and chemical fertilizer, T35+S+M+F]. The results showed that: 1) compared with the T15 treatment, maize yield was significantly increased by 15.4%-50.9% under fertile layer construction treatments. 2) There was no significant difference of soil pH among all treatments in the first two years, but fertile soil layer construction treatments significantly increased soil pH of topsoil (0-15 cm soil layer) in the third year. The pH of subsoil (15-35 cm soil layer) significantly increased under T35+S+M+F, T35+S+M, and T35+M treatments, while no significant difference was observed for T35+S treatment, compared with T15 treatment. 3) The fertile soil layer construction treatments could improve the nutrient contents of the topsoil and subsoil layer, especially in the subsoil layer, with the contents of organic matter, total nitrogen, available phosphorus, alkali-hydrolyzed nitrogen and available potassium being increased by 3.2%-46.6%, 9.1%-51.8%, 17.5%-130.1%, 4.4%-62.8%, 22.2%-68.7% under the subsoil layer, respectively. The fertility richness indices were increased in the subsoil layer, and nutrient contents of the subsoil layer were close to those of topsoil layer, indicating that 0-35 cm fertile soil layer had been constructed. 4) Soil organic matter contents in the 0-35 cm layer were increased by 8.8%-23.2% and 13.2%-30.1% in the second and third years of fertile soil layer construction, respectively. Soil organic carbon storage was also gradually increased under fertile soil layer construction treatments. 5) The carbon conversion rate of organic matter was 9.3%-20.9% under T35+S treatment, and 10.6%-24.6% under T35+M, T35+S+M, and T35+S+M+F treatments. The carbon sequestration rate was 815.7-3066.4 kg·hm-2·a-1 in fertile soil layer construction treatments. The carbon sequestration rate of T35+S treatment increased with experimental periods, and soil carbon content under T35+M, T35+S+M and T35+S+M+F treatments reached saturation point in the experimental second year. Construction of fertile soil layers could improve the fertility of topsoil and subsoil and maize yield. In term of economic benefits, combination application of maize straw, organic material and chemical fertilizer within 0-35 cm soil, cooperating with conservation tillage, is recommended for the Albic soil fertility improvement.

Analysis of the wall thickness of intracranial aneurysms: Can computational fluid dynamics detect the translucent areas of saccular intracranial aneurysms and predict the rupture risk preoperatively?

Background and purpose: The translucent area on the surface of intracranial aneurysms (IAs) is associated with rupture risk. In the present study, the Polyflow module of the Ansys software was used to simulate and analyze the thickness of the aneurysm wall to detect whether it was "translucent" and to assess the rupture risk. Methods: Forty-five patients with 48 IAs who underwent microsurgery were retrospectively reviewed. The medical records, radiographic data, and intraoperative images of the patients were collected. The image data were analyzed using computational fluid dynamics (CFD) simulations to explore the relationship between the simulated thickness of the aneurysm wall, the translucent area, and the rupture point of the real aneurysm's surface to predict the rupture risk and provide a certain reference basis for clinical treatment. Results: The Polyflow simulation revealed that the location of the minimum extreme point of the simulated aneurysm wall thickness was consistent with the translucent area or rupture point on the surface of the real aneurysm. There was a downward trend in the correlation between the change rate (IS) in the wall area and volume during aneurysm growth and rupture. Ruptured aneurysms have a greater inhomogeneity coefficient Iδ than the unruptured ones. In the unruptured group, translucent aneurysms also had greater inhomogeneity coefficients Iδ and more significant thickness changes (multiple IBA) than non-translucent ones. Conclusions: The Ansys software Polyflow module could detect whether the unruptured aneurysms were translucent and predict the rupture risk and rupture point. Clinical trial registration: https://clinicaltrials.gov/, Identifier, NCT03133624.

Association between suicide risk severity and sarcopenia in non-elderly Chinese inpatients with major depressive disorder.

BACKGROUND: Sarcopenia is a skeletal muscle disorder. Recent studies have shown an association between muscle health and suicide. However, there have been no previous studies on the relationship between suicide risk severity and sarcopenia in major depressive disorder (MDD). This study aimed to explore the association between suicide risk severity and sarcopenia in non-elderly Chinese inpatients with MDD. METHODS: The first-episode drug-naïve MDD inpatients aged 20-59 years with the 24-item Hamilton Rating Scale for Depression (HAMD-24) scores of >20 were included, who were then classified into low, intermediate, high and very high suicide risk groups according to the Nurses' Global Assessment of Suicide Risk (NGASR). The HAMD-24, the Hamilton Rating Scale for Anxiety (HAMA) and the SARC-F questionnaire were used to assess depression severity, anxiety severity and sarcopenia, respectively. The plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were measured. RESULTS: A total of 192 MDD inpatients (122 females, 70 males; aged 39.3 ± 11.7 years) were included, with 12.5% meeting criteria for sarcopenia. There were significant differences in gender, HAMD score and prevalence of sarcopenia among the suicide risk groups. Adjusted ordinal regression analysis showed that sarcopenia was significantly associated with more severe suicide risk (OR = 2.39, 95%CI 1.02-5.58, p = 0.044) independent of depression severity. CONCLUSIONS: This study revealed that sarcopenia was significantly associated with higher suicide risk in non-elderly Chinese MDD inpatients after adjustment for depression severity. Intervention of sarcopenia might be effective in reducing the risk of suicide in non-elderly MDD patients.

[Chlorination of Naproxen: Removal, Transformation and Risk Assessment].

The by-products produced during chlorination of pharmaceutically active compounds (PhACs) have created widespread public concern. Chlorination of a typical PhAC, naproxen (NAP), was studied. NAP chlorination parameters, intermediates identification, chlorination mechanism, and risk assessment during chlorination process have also been discussed. The results showed that NAP chlorination could fit well with the fist-order kinetics. The rate of removal and rate constants of NAP chlorination decreased with increasing initial NAP concentration and ammonium dosage, while these values increased with increasing initial free chlorine concentration. Acidic condition of the solution could significantly promote NAP chlorination. Five intermediates were identified by HPLC-MS/MS, and the mechanism of NAP chlorination was also put forward. Vibrio fischeri toxicity analysis and ESCOAR prediction indicated that higher toxicity intermediates were produced during NAP chlorination, which pose a potential threat to drinking water safety.

Blockade of Extracellular High-Mobility Group Box 1 Attenuates Systemic Inflammation and Coagulation Abnormalities in Rats with Acute Traumatic Coagulopathy.

BACKGROUND As an extracellularly released mediator, high-mobility group box 1 (HMGB1) initiates sterile inflammation following severe trauma. Serum HMGB1 levels correlate well with acute traumatic coagulopathy (ATC) in trauma patients, which is independently associated with higher mortality. We investigated the involvement of HMGB1 in ATC through blocking extracellular HMGB1. MATERIAL AND METHODS The ATC model was induced by polytrauma and hemorrhage in male Sprague-Dawley rats, which were randomly assigned to sham, ATC, and ATCH (ATC with HMGB1 blockade) groups. Thrombelastography (TEG) was performed to monitor changes in coagulation function. Serum levels of HMGB1, TNF-α, and IL-6 were measured, as well as lung levels of HMGB1 and nuclear factor (NF)-κB and expression of receptor for advanced glycation end-products (RAGE). RESULTS Compared with the sham group, HMGB1 increased the serum levels of TNF-α and IL-6, whereas HMGB1 blockade inhibited the induction of TNF-α and IL-6. HMGB1 also induced elevated serum soluble P-selectin and fibrinolysis markers plasmin-antiplasmin complex, which both were reduced by HMGB1 blockade. Thrombelastography revealed the hypocoagulability status in the ATC group, which was attenuated by anti-HMGB1 antibody. Furthermore, the lung level of NF-κB and expression of RAGE were decreased by anti-HMGB1 antibody, suggesting the role of RAGE/NF-κB pathway in ATC. CONCLUSIONS HMGB1 blockade can attenuate inflammation and coagulopathy in ATC rats. Anti-HMGB1 antibody might exert protective effects partly through the RAGE/NF-κB pathway. Thus, HMGB1 has potential as a therapeutic target in ATC.

Upregulated dynamin 1 in an acute seizure model and in epileptic patients.

Dynamin 1 is a neuron-specific guanosine triphosphatase (GTPase) that is an essential component of membrane fission during synaptic vesicle recycling and endocytosis. This study evaluated the dynamin 1 expression pattern in the acute lithium-pilocarpine rat model and in patients with temporal lobe epilepsy (TLE) and investigated whether altering the dynamin 1 expression pattern affects epileptic seizures in vivo and in vitro. The immunofluorescence, western blot analysis, and reverse transcription-PCR results show that the dynamin 1 expression level increased significantly in experimental rats from day 1 to day 7 after the onset of seizures and was significantly higher in TLE patients. The behavioral study revealed that inhibiting dynamin 1 increased the latency time of the first seizure and decreased the frequency and severity of the seizures. In addition, electrophysiological recordings from brain slices showed that inhibiting dynamin 1 reduces the frequency of Mg-free induced seizure-like activity. The anticonvulsant effect of dynasore was more effective at 10 µM than at 1 µM or 160 µM. These results indicate that the altered level of dynamin 1 may contribute to the development of epileptic seizures and that the targeted regulation of dynamin 1 activity may control epileptic seizures.

Delayed liver laceration following transjugular intrahepatic portosystemic shunt for portal hypertension.

The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has proven benefits in the treatment of patients who have complications from portal hypertension due to liver cirrhosis. Delayed liver laceration is a rare complication of the TIPS procedure. We describe a patient with portal hypertension due to liver cirrhosis, who suddenly presented with abdominal hemorrhage and liver laceration 8 d after TIPS. Few reports have described complications after TIPS placement. To the best of our knowledge, this is the first report describing delayed liver laceration. This potential and serious complication appears to be specific and fatal for TIPS in portal hypertension. We advocate careful attention to the technique to avoid this complication, and timely treatment is extremely important.

[Preliminary study of Sub-Health Measurement Scale Version1.0 norms for Chinese civil servants].

OBJECTIVE: To establish the norms of Sub-Health Measurement Scale Version1.0 (SHMS V1.0) for Chinese civil servants. METHODS: We sampled a total of 15 000 civil servants form Tianjin (north China), Guangdong (south China), Anhui and Hunan (central China), Xinjiang (northwest China) and Shenyang (northeast China) to perform the spot trial, and established the mean, percentile and threshold norms based on the characteristics of SHMS V1.0 scores for Chinese civil servants. RESULTS: The established norms based on the average scores of SHMS V1.0 showed a mean score of 66.55∓12.36 for young male subjects (below 40 years), 67.42∓12.40 for older male subjects, 66.22∓11.81 for female subjects younger than 40 years, and 65.94∓11.91 for older female subjects. The threshold norms of SHMS V1.0 divided 5 health states, namely disease, severe sub-health, moderate sub-health, mild sub-health and healthy states according to the Mean∓SD and Mean∓0.5SD of the converted scores. The 4 cut-off points were close to the 15th, 30th, 70th and 85th percentile scores of SHMS V1.0. CONCLUSION: We have established SHMS V1.0 norms for Chinese civil servants, which facilitates further investigation of the incidence of sub-health state and its contributing factors in civil servants.

[Dental anomalies in Chinese children with complete unilateral cleft lip and palate].

OBJECTIVE: To investigate the prevalence of dental anomalies in Chinese children with complete unilateral cleft lip and palate (UCLP). METHODS: Dental histories and radiographs of 244 Chinese children with UCLP were collected. The diagnosis of dental anomalies was based on panoramic radiographs before alveolar bone grafting. All patients were over 8 years old. RESULTS: In the UCLP group, 66.8% of the patients was presented with hypodontia. The maxillary lateral incisors were the most common teeth affected, followed by maxillary second premolars, mandibular incisors and mandibular second premolars. A total of 33.6% the patients was presented with dental malformation, most were microdontic laterel incisors. A total of 4.9% the patients was presented with hyperdontia. The supernumerary teeth were more frequently found in the cleft region. The prevalence of missing maxillary lateral incisor in the noncleft side was statistically different between genders, which was higher in male (P < 0.050). This group of Chinese children with UCLP demonstrated significantly higher prevalence of hypodontia, hyperdontia, and malformation on the cleft side than on the noncleft side (P < 0.01). CONCLUSIONS: Hypodontia is the most common type of dental anomalies. The prevalence of dental anomalies is higher in the UCLP patients than in the normal population. Dental anomalies occur more frequently on the cleft side than on the noncleft side.