Physiological, cytological and multi-omics analysis revealed the molecular response of Fritillaria cirrhosa to Cd toxicity in Qinghai-Tibet Plateau.

Fritillaria cirrhosa, an endangered plant endemic to plateau regions, faces escalating cadmium (Cd) stress due to pollution in the Qinghai-Tibet Plateau. This study employed physiological, cytological, and multi-omics techniques to investigate the toxic effects of Cd stress and detoxification mechanisms of F. cirrhosa. The results demonstrated that Cd caused severe damage to cell membranes and organelles, leading to significant oxidative damage and reducing photosynthesis, alkaloid and nucleoside contents, and biomass. Cd application increased cell wall thickness by 167.89% in leaves and 445.78% in bulbs, leading to weight percentage of Cd increases of 76.00% and 257.14%, respectively. PER, CESA, PME, and SUS, genes responsible for cell wall thickening, were significantly upregulated. Additionally, the levels of metabolites participating in the scavenging of reactive oxygen species, including oxidized glutathione, D-proline, L-citrulline, and putrescine, were significantly increased under Cd stress. Combined multi-omics analyses revealed that glutathione metabolism and cell wall biosynthesis pathways jointly constituted the detoxification mechanism of F. cirrhosa in response to Cd stress. This study provides a theoretical basis for further screening of new cultivars for Cd tolerance and developing appropriate cultivation strategies to alleviate Cd toxicity.

Replacement of Loops at the Entrance of the Active Pocket of Streptococcus thermophilus 4,6-α-Glucanotransferase Changes Its Catalytic Activity and Product Specificity.

To explore the roles of loops around active pocket in the reuteran type 4,6-α-glucanotransferase (StGtfB) from S. thermophilus, they were individually or simultaneously replaced with those of an isomalto/maltopolysaccharides type 4,6-α-glucanotransferase from L. reuteri. StGtfB with the replaced loops A1, A2 (A1A2) and A1, A2, B (A1A2B), respectively, showed 1.41- and 0.83-fold activities of StGtfB. Two mutants reduced crystallinity and increased starch disorder at 2, 4, and 8 U/g more than StGtfB and increased DP ≤ 5 short branches of starch by 38.01% at 2 U/g, much more than StGtfB by 4.24%. A1A2B modified starches had the lowest retrogradation over 14 days. A1A2 modified starches had the highest percentage of slowly digestible fractions, ranging from 40.32% to 43.34%. StGtfB and its mutants bind substrates by hydrogen bonding and van der Waals forces at their nonidentical amino acid residues, suggesting that loop replacement leads to a different conformation and changes activity and product structure.

Contezolid-Containing Regimen Successfully Treated Multiple Drug Resistance Mycobacterium Abscessus Complex Infection of Skin: A Case Report and Literature Review.

Background: In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM globally present significant challenges, particularly in cases involving Mycobacterium abscessus complex (MABC) infection where effective therapeutic options are limited. Case Presentation: We reported a 38-year-old female patient who was infected with MABC of skin due to "beauty needle" at a beauty salon, with mass on both cheeks, accompanied by redness, and pain, and some of them was ulcered and effused. Puncture pumping pus from bilateral cheek mass for many times, rinsed with "metronidazole", and oral "cephalosporin" treatment did not work. Therefore, she came to our hospital. MABC was detected in abscess paracentesis pus by nucleic acid mass spectrometry, and was proved by the cultured result of the pus. Thus, the patient was diagnosed as skin MABC infection, and anti-NTM treatment was taken. However, adverse reactions such as tinnitus, hepatotoxicity and neurovirulence occurred during the initial treatment. After adjusting to the contezolid-containing regimen, these adverse reactions improved. After nearly 6 months of treatment, the cheek mass was gradually reduced and the skin ruptures were gradually healed. Follow-up for 10 months showed that the patient's facial symptoms were significantly improved, and no drug-related adverse reactions happened. Conclusion: This was the first successful case of multiple drug resistance MABC infection of skin treated with contezolid-containing antibiotic management strategies, which exhibited remarkable efficacy and good safety in this intractable disease.

The positivity rates and drug resistance patterns of Mycobacterium tuberculosis using nucleotide MALDI-TOF MS assay among suspected tuberculosis patients in Shandong, China: a multi-center prospective study.

Objective: To investigate the positivity rates and drug resistance characteristics of Mycobacterium tuberculosis (MTB) among suspected tuberculosis (TB) patients in Shandong Province, the second-largest population province in China. Methods: A prospective, multi-center study was conducted from April 2022 to June 2023. Pathogen and drug resistance were identified using nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS). Results: Of 940 suspected TB patients included in this study, 552 cases were found to be infected with MTB giving an overall positivity rate of 58.72%. Total of 346 cases were resistant to arbitrary anti-TB drug (62.68%), with Zibo (76.47%), Liaocheng and Weihai (both 69.23%) ranking top three and TB treatment history might be a related factor. Monoresistance was the most common pattern (33.53%), with isoniazid the highest at 12.43%, followed by rifampicin at 9.54%. Further analysis of gene mutations conferring resistance revealed diverse types with high heteroresistance rate found in multiple anti-TB drugs. Conclusion: A relatively high rate of MTB positivity and drug resistance was found in Shandong Province during and after the COVID-19 pandemic, indicating the need for strengthening rapid identification of species and drug resistance among suspected TB patients to guide better medication and minimize the occurrence of drug resistance.

Phase selectivity and tunable photophysical nature of rare earth metal-organic frameworks of EuxY1-x-PTC (H3PTC = 2,4,6-pyridine tricarboxylic acid; x = 0-1).

Two rare earth metal-organic frameworks (MOFs), [Y2(PTC)2(H2O)2]·3H2O (Y-PTC) and [Eu2(PTC)2(H2O)5]·H2O (Eu-PTC) together with the solid solutions [Eu2xY2(1-x)(PTC)2(H2O)5]·H2O (EuxY1-x-PTC, x = 0.013-0.82), were synthesized hydrothermally, and characterized by microanalysis, IR spectroscopy, TG, powder, and single crystal X-ray diffraction techniques. Eu-PTC and Y-PTC showed different crystal structures; however, all solid solutions were isomorphic to Eu-PTC even at x = 0.013, leading to the IR spectra and TG plots of the solid solutions to be similar to those of Eu-PTC but distinct from those of Y-PTC. DFT calculations for the crystal lattice energy demonstrated that the procedure for the crystallizing nucleation of Eu-PTC occurred prior to that of Y-PTC in the reaction solution, leading to the all solid solutions being isomorphic to Eu-PTC. The solid emission spectra at ambient condition showed that Y-PTC emitted ligand-based phosphorescence at 433 nm with a quantum yield (QY) of 27.02%, while Eu-PTC and EuxY1-x-PTC (x = 0.013-0.82) emitted the characteristic luminescence of Eu3+ ions, and most solid solutions showed higher QYs than Eu-PTC; in particular, the QY of Eu0.195Y0.805-PTC was up to 29.48%, i.e., increased by 10% regarding Eu-PTC (19.86%). Interestingly, solid solutions with x = 0.013-0.395 showed excitation-wavelength-dependent luminescence, and such type of luminescence MOFs have promising applications including the areas of precise temperature, gas sensing and information encryption or anti-counterfeiting materials.

Crystal Structures, Photoluminescence, and Magnetism of Two Novel Transition-Metal Complex Cocrystals with Three-Dimensional H-Bonding Organic Framework or Alternating Noncovalent Anionic and Cationic Layers.

Cocrystallization may alter material physicochemical properties; thus, the strategy of forming a cocrystal is generally used to improve the material performance for practical applications. In this study, two transition-metal complex cocrystals [Zn(bpy)3]H0.5BDC·H1.5BDC·0.5bpy·3H2O (1) and [Cu2(BDC)(bpy)4]BDC·bpy·2H2O (2) have been achieved using a hydrothermal reaction, where bpy and H2BDC represent 2,2'-bipyridine and benzene-1,3-dicarboxylic acid, respectively. Cocrystals were characterized by microanalysis, infrared spectroscopy, and UV-visible spectroscopy. Cocrystal 1 contains five components and crystallizes in a monoclinic space group P21/n. The H0.5BDC1.5-, H1.5BDC0.5-, and H2O molecules construct three-dimensional H-bonding organic framework; the [Zn(bpy)3]2+ coordination cations and uncoordinated bpy molecules reside in channels, where two coordinated bpy ligands in [Zn(bpy)3]2+ and one uncoordinated bpy adopt sandwich-type alignment via π···π stacking interactions. Cocrystal 2 with four components crystallizes in a triclinic space group P-1 to form alternating layers; the binuclear [Cu2(bpy)4(BDC)]2+ cations and uncoordinated bpy molecules build the cationic layers, and the BDC2- species with disordered lattice water molecules form the anionic layers. Cocrystal 1 shows intense photoluminescence at an ambient condition with a quantum yield of 14.96% and decay time of 0.48 ns, attributed to the π* → π electron transition within phenyl/pyridyl rings, and 2 exhibits magnetic behavior of an almost isolated spin system with rather weak antiferromagnetic coupling in the [Cu2(bpy)4(BDC)]2+ cation.

Stereochemically Active and Inactive Lone Pairs in Two Room-Temperature Phosphorescence Coordination Polymers of Pb2+ with Different Tricarboxylic Acids.

Two new Pb2+-based coordination polymers (CPs), [Pb2(HBTC)2(DMF)] (1) and [Pb(HPTC)] (2), have been synthesized under solvothermal condition; herein, H3BTC and H3PTC represent 1,3,5-benzenetricarboxylic acid and 2,4,6-pyridine tricarboxylic acid, respectively. Both 1 and 2 were characterized by microanalysis, infrared spectra (IR), thermal gravimetric analyses (TGA), and powder X-ray diffraction (PXRD) techniques. Single-crystal structural analysis indicates that 1 and 2 show different coordination sphere around Pb2+ ions and distinct coordination frameworks. The I1O2 type three-dimensional (3D) nonporous metal-organic framework forms in 1, where the Pb2+ ion shows holo-directed coordination geometry, while the I0O2 type two-dimensional (2D) coordination polymeric layered structure forms in 2, where Pb2+ ion shows a hemidirected coordination sphere and the 6s2 lone electron pair in Pb2+ ion is stereochemically active. The two CPs emit intense and long-lasting greenish phosphorescence in air at room temperature, with absolute quantum yields of 1.2% for 1 and 4.7% for 2 and decay lifetimes of 0.73 ms for 1 and 1.52 ms for 2.

Short-course Regimen for Subsequent Treatment of Pulmonary Tuberculosis: A Prospective, Randomized, Controlled Multicenter Clinical Trial in China.

PURPOSE: We designed a prospective, multicenter, randomized, controlled study to assess a 5-month regimen compared with the standard regimen on previously treated patients with pulmonary tuberculosis (TB). METHODS: We enrolled 917 sputum smear-positive patients undergoing additional treatment in 27 major tuberculosis hospitals in China. Patients were randomly assigned to a test group (n = 626)treated with a 5-month regimen of moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide or a reference group (n = 291) treated with an 8-month regimen of isoniazid, rifampicin, and streptomycin. All patients with a favorable response were followed up for 5 years after the end of treatment. FINDINGS: Of the study patients, 61 in the test group and 19 in the reference group had multidrug-resistant (MDR) TB. The treatment success rate in the study group was 74.12%, which was significantly higher than the 67.70% in the reference group (P = 0.04), whereas the treatment success rate of patients with MDR-TB was not significantly different between the test and reference groups (70.5% vs 63.1%, P =0.79). The adverse effects rates in the test and reference groups were 7.4% and 3.1%, respectively (P = .01). The difference in the TB recurrence rates between the group arm (9.6%) and the reference group (21.8%) was statistically significant (P < 0.001). IMPLICATIONS: The moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide test regimen yielded higher success and lower recurrence rates than the currently recommended isoniazid, rifampicin, and streptomycin regimen, but the rate of adverse effects was higher. ClinicalTrials.gov identifier: NCT02331823.

Role of medical thoracoscopy in the treatment of tuberculous pleural effusion.

BACKGROUND: Fibrous tuberculous pleural effusion (TPE) represents common disease in tuberculous clinic. Medical thoracoscopy has been used to treat pleural empyema and shown promising outcomes, but data of its use in multiloculated and organized TPE remains limited to know. METHODS: The study was performed on 430 cases with TPE. The cases were divided into free-flowing, multiloculated effusion and organized effusion group. Each group was subdivided into two or three types of therapeutic approaches: ultrasound guided pigtail catheter, large-bore tube chest drainage and medical thoracoscopy. Patients with multiloculated or organized effusions received streptokinase, introduced into the pleural cavity via chest tubes. The successful effectiveness of the study was defined as duration of chest drainage, time from treatment to discharge days and no further managements. RESULTS: Patients with organized effusion were older than those with free-flowing effusion and incidence of organized effusion combined with pulmonary tuberculosis (PTB) was higher than those of multiloculated effusion and free-flowing effusion respectively. Positive tuberculosis of pleural fluid culture was higher in organized effusion than that in free-flowing effusion. Sputum positive for acid-fast bacillus (AFB) in organized effusion was higher than that in multiloculated effusion and free-flowing effusion. Medical thoracoscopy showed significant efficacy in the group of multiloculated effusion and organized effusion but free-flowing effusion. No chronic morbidity and mortality related to complications was observed. CONCLUSIONS: Medical thoracoscopy was a safe and successful method in treating multiloculated and organized TPE.

An open-label, randomized and multi-center clinical trial to evaluate the efficacy of Silibinin in preventing drug-induced liver injury.

UNLABELLED: To assess the clinical efficacy and safety of Silibinin in preventing drug-induced liver injury (DILI) in the general population (high-risk patients with non-drug induced liver injury). METHOD: A prospective, multi-center, randomized, open-label and controlled trial was conducted with 568 patients undergoing primary treatment of pulmonary tuberculosis. The study included 277 patients in experimental group and 291 patients in control group. The patients in the two group were treated with conventional 2HREZ (S)/4HR for tuberculosis (TB), and additional Silibinin capsules (oral administration of 70 mg/time, 3 times/day for 8 weeks in experimental group. Outcomes of liver function, interruption of anti-TB treatment and therapeutic results, as well as adverse reactions were observed and analyzed. RESULTS: At 2, 4 and 8 weeks of treatment, the incidences of liver injury in experimental group were 3.97%, 1.44% and 2.17%, respectively; the incidences in control group were 4.12%, 4.12% and 2.41%, respectively. Statistical analysis showed that there was no difference in the incidence between the two groups at each treatment period (P>0.05). At 8 weeks, the numbers of patients diagnosed of DILI were 18 (7.22%) and 27 (9.28%) in experimental and control groups, respectively (P>0.05). 34.30% and 27.49% of the patients in experimental and control groups had transient abnormal liver function or symptoms, respectively; similar percentages (3.25% and 6.19%) of the patients in two groups have liver function injury and symptoms, and were suspended for anti-TB treatment (P>0.05). The incidence of anorexia and nausea symptoms was lower in experimental group than in control group, and the differences were significant at 4 and 8 weeks (P<0.05). 8 weeks after the treatment, 98.30% of the sputum smear culture were negative in experimental group, which was significantly higher (P<0.01) than that in control group (92.98%). CONCLUSION: Preventive hepatoprotective therapy in the general population may reduce drug discontinuation rate, improve patient's compliance and outcomes of anti-TB treatment.

N-glycosylation of effector proteins by an α-1,3-mannosyltransferase is required for the rice blast fungus to evade host innate immunity.

Plant pathogenic fungi deploy secreted effectors to suppress plant immunity responses. These effectors operate either in the apoplast or within host cells, so they are putatively glycosylated, but the posttranslational regulation of their activities has not been explored. In this study, the ASPARAGINE-LINKED GLYCOSYLATION3 (ALG3)-mediated N-glycosylation of the effector, Secreted LysM Protein1 (Slp1), was found to be essential for its activity in the rice blast fungus Magnaporthe oryzae. ALG3 encodes an α-1,3-mannosyltransferase for protein N-glycosylation. Deletion of ALG3 resulted in the arrest of secondary infection hyphae and a significant reduction in virulence. We observed that Δalg3 mutants induced massive production of reactive oxygen species in host cells, in a similar manner to Δslp1 mutants, which is a key factor responsible for arresting infection hyphae of the mutants. Slp1 sequesters chitin oligosaccharides to avoid their recognition by the rice (Oryza sativa) chitin elicitor binding protein CEBiP and the induction of innate immune responses, including reactive oxygen species production. We demonstrate that Slp1 has three N-glycosylation sites and that simultaneous Alg3-mediated N-glycosylation of each site is required to maintain protein stability and the chitin binding activity of Slp1, which are essential for its effector function. These results indicate that Alg3-mediated N-glycosylation of Slp1 is required to evade host innate immunity.

Hg2+-selective ratiometric and "off-on" chemosensor based on the azadiene-pyrene derivative.

A new pyrene-based derivative bearing an azadiene group was synthesized as a ratiometric chemosensor for Hg(2+) in aqueous acetonitrile solution. The "off-on" type signaling behavior of the fluoroionophore is due to the metal ion induced conformational changes from the weak pyrene monomer emissions to strong pyrene excimer emission.

[The clinical significance of serum tuberculosis specific antigen antibody in the diagnosis of tuberculosis].

OBJECTIVE: To evaluate the significance of serum tuberculosis specific antigen (TB-SA) antibody detection in the diagnosis of tuberculosis. METHODS: TB-SA antibody in the serum samples from 829 cases of tuberculosis, 278 patients with non-tuberculosis lung diseases and 125 healthy volunteers were detected using enzyme-linked immunosorbent assay (ELISA). Tuberculosis was confirmed by clinical, bacteriology, X-ray examination and pathology studies. RESULTS: The sensitivity of TB-SA antibody in diagnosis of bacteriologically positive and negative pulmonary tuberculosis and extrapulmonary tuberculosis was 75.1% (272/362), 68.9% (226/328) and 71.2% (99/139), respectively; the combined sensitivity was 72.0% (597/829), and the specificity 82.1% (331/403). The relationship between the OD(405) of TB-SA antibody and PPD positivity showed no linear relationship, suggesting that BCG vaccination did not affect the value of serum TB-SA antibody. CONCLUSION: The results suggest that measurement of serum TB-SA is a relatively sensitive and specific method for the diagnosis and differential diagnosis of tuberculosis.