Food-Borne Biotoxin Neutralization in Vivo by Nanobodies: Current Status and Prospects.

Food-borne biotoxins from microbes, plants, or animals contaminate unclean, spoiled, and rotten foods, posing significant health risks. Neutralizing such toxins is vital for human health, especially after food poisoning. Nanobodies (Nbs), a type of single-domain antibodies derived from the genetic cloning of a variable domain of heavy chain antibodies (VHHs) in camels, offer unique advantages in toxin neutralization. Their small size, high stability, and precise binding enable effective neutralization. The use of Nbs in neutralizing food-borne biotoxins offers numerous benefits, and their genetic malleability allows tailored optimization for diverse toxins. As nanotechnology continues to evolve and improve, Nbs are poised to become increasingly efficient and safer tools for toxin neutralization, playing a pivotal role in safeguarding human health and environmental safety. This review not only highlights the efficacy of these agents in neutralizing toxins but also proposes innovative solutions to address their current challenges. It lays a solid foundation for their further development in this crucial field and propels their commercial application, thereby contributing significantly to advancements in this domain.

In vitro simulated digestion and fermentation characteristics of pectic polysaccharides from fresh passion fruit (Passiflora edulis f. flavicarpa L.) peel.

In this study, two pectic polysaccharides (PFP-T and PFP-UM) were extracted from fresh passion fruit peels using three-phase partitioning (TPP) and sequential ultrasound-microwave-assisted TPP methods, respectively, and their effects on the in vitro gastrointestinal digestion and fecal fermentation characteristics were examined. The results indicate that gastrointestinal digestion has a minimal effect on the physicochemical and structural characteristics of PFP-T and PFP-UM. However, during in vitro fecal fermentation, both undigested PFP-T and PFP-UM are significantly degraded and utilized by intestinal microorganisms, showing increased the total relative abundance of Firmicutes and Bacteroidota in the intestinal flora. Notably, compared with PFP-UM, PFP-T better promoted the reproduction of beneficial bacteria such as Prevotella, Megasphaera and Dialister, while suppressed the growth of harmful genera including Escherichia-Shigella, producing higher content of short-chain fatty acids. Therefore, our findings suggest that PFP-T derived from passion fruit peel has potential as a dietary supplement for promoting intestinal health.

Triethyl amine as an effective reducing agent for sulfoxide deoxygenation.

Enabled by triethyl amine (Et3N) and thionyl chloride (SOCl2), an efficient and practical protocol for deoxygenation of sulfoxide to sulfide was developed. This new method features a wide range of substrate scope, including diaryl, dialkyl and aryl alkyl substituted sulfoxides. Detailed mechanistic investigations reveal the crucial role played by Et3N as an electron-donating reductant rather than a hydrogen-atom donor.

Highly Enantioselective Dihydroxylation of 1,1-Disubstituted Aliphatic Alkenes Enabled by Orchestrated Noncovalent π-Interactions.

The elusive nature of noncovalent π-interactions leads to their infrequent use as a design element in challenging chemical reactions. Stereocontrolling models based on coordinated noncovalent π-interactions were used for the asymmetric dihydroxylation of 1,1-disubstituted aliphatic alkenes. By introduction of a substituted phthalazine ring into the alkene substrates, the enantioselectivity reached 99% under the catalysis of bis-cinchona alkaloid ligands. Density functional theory calculations indicated a well-orchestrated, π-π interaction-directed "sandwich-like" transition state.

[Tonglong Kaibi Prescription for the treatment of severe benign prostate hyperplasia: A clinical study].

OBJECTIVE: To evaluate the clinical effect of the traditional Chinese medicine (TCM) Tonglong Kaibi Prescription (TKP) in the treatment of severe BPH with kidney deficiency and blood stasis combined with damp heat syndrome. METHODS: We randomly divided 120 cases of severe BPH with kidney deficiency and blood stasis combined with damp heat syndrome into three groups of equal number, treated with TKP, doxazosin mesylate sustained-release tablets (the DM control), and TKP + DM, all for 8 weeks. We obtained the IPSS, TCM symptoms scores, quality of life (QOL) scores, maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) from the patients before and after treatment and compared them among the three groups. RESULTS: After 8 weeks of treatment, the effectiveness rate was significantly higher in the TKP + DM than in the DM control group (P < 0.05). The IPSS, TCM symptoms scores, QOL scores and PVR decreased (P < 0.01), while the Qmax increased dramatically (P < 0.01) in all the three groups. Pairwise comparison showed that the IPSS and QOL scores were lower in the TKP + DM than in the TKP and DM control groups (P < 0.05 or 0.01), and so were the TCM syndrome scores in the TKP + DM and TKP groups than in the DM control (P < 0.01). There were no statistically significant differences in PVR and Qmax among the three groups after treatment (P> 0.05), and no serious adverse events during the treatment. CONCLUSION: TKP is safe and effective in the treatment of severe BPH, which can improve the TCM symptoms, reduce the IPSS, QOL scores and PVR and increase the Qmax of the patients. TKP is evidently superior to DM alone in improving TCM symptoms of BPH and combined medication of TKP and DM produces even better clinical efficacy.

Engineered non-covalent π interactions as key elements for chiral recognition.

Molecular recognition and self-assembly are often mediated by intermolecular forces involving aromatic π-systems. Despite the ubiquity of such interactions in biological systems and in the design of functional materials, the elusive nature of aromatic π interaction results in that they have been seldom used as a design element for promoting challenging chemical reactions. Described here is a well-engineered catalytic system into which non-covalent π interactions are directly incorporated. Enabled by a lone pair-π interaction and a π-π stacking interaction operating collectively, efficient chiral recognition is successfully achieved in the long-pursued dihydroxylation-based kinetic resolution. Density functional theory calculations shed light on the crucial role played by the lone pair-π interaction between the carbonyl oxygen of the cinchona alkaloid ligand and the electron-deficient phthalazine π moiety of the substrate in the stereoselectivity-determining transition states. This discovery serves as a proof-of-principle example showing how the weak non-covalent π interactions, if ingeniously designed, could be a powerful guide in attaining highly enantioselective catalysis.

[Pricking-reinforcing -reducing therapy improves semen quality and seminal plasma biochemical indexes in patients with varicocele infertility].

OBJECTIVE: To investigate the effect of pricking-reinforcing -reducing therapy (PRRT) on the semen quality and seminal plasma biochemical indexes of varicocele (VC) infertility patients. METHODS: We randomly and equally assigned 160 patients with VC infertility into a PRRT and a control group, the former treated by PRRT and the latter with oral ShengjingCapsules. Before and after treatment, we obtained the semen parameters, sperm morphology, sperm survival rate, sperm acrosin activity, seminal plasma neutral α glucosidase and seminal plasma zinc in the patients and compared them between the two groups. RESULTS: Before treatment, there were no statistically significant differences between the PRRT and control groups in sperm concentration (ï¼»16.81 ± 7.83ï¼½ vs ï¼»16.80 ± 7.54ï¼½ ×106 /ml, P > 0.05), total sperm count (ï¼»42.01 ± 19.57ï¼½ vs ï¼»41.99 ± 18.84ï¼½ ×106, P > 0.05), percentages of progressively motile sperm (PMS) (ï¼»15.37 ± 11.03ï¼½% vs ï¼»14.68 ± 10.27ï¼½%, P > 0.05) and morphologically normal sperm ( MNS) (1.62 ± 1.51ï¼½% vs ï¼»1.62 ± 1.13ï¼½%, P > 0.05), sperm survival rate (ï¼»28.11 ± 18.95ï¼½% vs ï¼»28.23±18.38ï¼½%, P > 0.05) and sperm acrosin activity (ï¼»28.11 ± 14.64ï¼½ vs ï¼»27.19 ± 14.07ï¼½ U/L, P > 0.05). After three months of treatment, all the patients showed evident increases in the above parameters (P < 0.05), even higher in the PRRT than in the control group, more significantly in sperm concentration (ï¼»38.88 ± 30.54ï¼½ vs ï¼»25.60 ± 14.71ï¼½ ×106 /ml, P < 0.05), PMS (ï¼»32.60 ± 12.46ï¼½% vs ï¼»27.67 ± 12.27ï¼½%, P < 0.05) and sperm acrosin activity (ï¼»65.74±31.81ï¼½ vs ï¼»67.94±17.95ï¼½ U/L, P < 0.05), though not significantly in total sperm count (97.20 ± 76.35ï¼½ vs ï¼»88.19 ± 39.56ï¼½ ×106, P > 0.05), MNS (ï¼»2.35 ± 1.83ï¼½% vs ï¼»1.87 ± 1.20ï¼½%, P > 0.05) and sperm survival rate (ï¼»61.44 ± 20.02ï¼½% vs ï¼»59.12 ± 22.48ï¼½%, P > 0.05). Compared with the baseline, after treatment, the patients in the PRRT group also exhibited elevated levels of neutral α-glucosidase (ï¼»14.42 ± 5.90ï¼½ vs ï¼»28.43 ± 19.76ï¼½ U/L, P < 0.05) and seminal plasma zinc (ï¼»2.11 ± 1.22ï¼½ vs ï¼»2.89 ± 1.23ï¼½ mmol/L, P < 0.05), and so did the controls (ï¼»14.44 ± 5.61ï¼½ vs ï¼»26.66 ± 17.69ï¼½ U/L , P < 0.05) and (ï¼»2.09 ± 1.10ï¼½ vs ï¼»2.82±1.08ï¼½ mmol/L, P < 0.05). No statistically significant difference, however, was observed between the two groups after treatment (P > 0.05). CONCLUSION: PRRT can significantly improve semen quality in patients with VC infertility, even more effective than ShengjingCapsules in improving sperm concentration, PMS, sperm survival rate, and sperm acrosin activity, which may be related to its effect of elevating the levels of seminal plasma neutral-α glucosidase and zinc providing sufficient energy for basic sperm metabolism, maturation, energy acquisition and motility.

[Danhong Tongjing Prescription versus microsurgery in the treatment of varicocele-induced infertility: A retrospective multivariate analysis of 218 cases].

OBJECTIVE: To compared the traditional Chinese medicine Danhong Tongjing Prescription (DTP) and microsurgery in the treatment of varicocele (VC)-induced infertility and investigate the factors influencing the recovery of semen parameters of the patients. METHODS: We retrospectively analyzed the clinical data on 218 cases of VC-induced infertility with qi-deficiency and blood-stasis treated with DTP (n = 86) or by microsurgery (n = 132) in our hospital from January 2017 to July 2019, and compared the semen parameters between the two groups of patients after treatment. With age, course of disease, degree of VC, change of the testis volume, estrogen/testosterone (E/T) ratio and levels of FSH and LH as independent variables, and increased semen parameters after treatment as dependent variables, we constructed a multivariate linear regression model and identified statistically significant independent variables. RESULTS: After treatment, sperm concentration and the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS) were obviously improved in both the DTP and microsurgery groups, with statistically significant difference between the two groups in sperm concentration and MNS, but not in PMS. Linear regression analysis showed that the severity of VC was an influencing factor for the recovery of sperm concentration after treatment in the DTP group (r = －11.599, Ra2 = 0.044 9) and the course of VC infertility was a factor affecting the recovery of sperm count in the microsurgery group (r = －1.837, Ra2 = 0.035 7). CONCLUSION: DTP is comparable to microsurgery in improving sperm motility while microsurgery is more effective in increasing the percentage of MNS in the treatment of VC-induced infertility. Early surgery is recommended for the treatment of infertility induced by severe bilateral VC, and DTP can be selected for infertility caused by mild or moderate bilateral VC if the patient is unwilling to accept surgery or microsurgery is inaccessible in the hospital.

[Magnetic resonance and magnetoelectric therapy combined with Danhong Tongjing Prescription for the treatment of CP/CPPS and its effects on secretory IgA, vascular cell adhesion molecule-1 and interleukin-8].

OBJECTIVE: To investigate the therapeutic effect of magnetic resonance and magnetoelectric therapy (MRMT) combined with oral Danhong Tongjing Prescription (DTP) on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) and the changes in the levels of cytokine-secretory IgA (sIgA), vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) after treatment. METHODS: Totally 200 patients with CP/CPPS of the qi stagnation and blood stasis type were randomly divided into three groups to receive MRMT + DTP (n = 68), MRMT (n = 67) and DTP (n = 65), respectively, all for 12 weeks. After treatment, we compared the total effectiveness rate, patients' scores on NIH-CPSI and traditional Chinese medicine (TCM) syndrome, and the expressions of sIgA, VCAM-1 and IL-8 in the EPS among the three groups of the patients. RESULTS: After treatment, the patients in the MRMT + DTP group, compared with those in the MRMT and DTP groups, showed a significantly higher total effectiveness rate (86.76% vs 79.10% and 78.46%, P < 0.05 and P < 0.01) and lower scores on pain or discomfort (4.61 ± 2.37 vs 5.86 ± 3.26 and 6.94 ± 2.25 P < 0.01), abnormal urination symptoms (2.98 ± 1.75 vs 3.85 ± 2.01 and 3.94 ± 1.95) and quality of life (3.26 ± 1.87 vs 4.54 ± 2.13 and 4.69 ± 1.72). There were statistically significant differences in the total NIH-CPSI scores among the three groups (10.64 ± 5.91 vs 4.59 ± 6.87 vs 15.54 ± 5.76, P < 0.05). The MRMT + DTP group also exhibited a remarkably lower TCM syndrome score than the MRMT and DTP groups (5.56 ± 3.42 vs 7.37 ± 4.57 and 8.16 ± 3.65, P < 0.05). Compared with the baseline, the expressions sIgA, VCAM-1 and IL8 were all markedly decreased after treatment in the MRMT + DTP (Z = －7.170, Z = －7.182, Z = －7.18), MRMT (Z = －6.802, Z = －6.973, Z = －6.768) and DTP groups (Z = －5.963, Z = －6.990 Z = －5.618) (P < 0.05), even more significantly in the former than in the latter two groups (P < 0.05). CONCLUSION: Magnetic resonance and magnetoelectric therapy combined with Danhong Tongjing Prescription has a good therapeutic effect on CP/CPPS of the qi stagnation and blood stasis type, probably by regulating sIgA, VCAM-1, IL-8 and other cytokines, activating the function of the immune system, inhibiting inflammation, and promoting the absorption of local inflammatory substances.

Simultaneous Kinetic Resolution and Asymmetric Induction within a Borrowing Hydrogen Cascade Mediated by a Single Catalyst.

The mechanistic uniqueness and versatility of borrowing hydrogen catalysis provides an opportunity to investigate the controllability of a cascade reaction, and more importantly, to realize either one or both of chiral recognition and chiral induction simultaneously. Here we report that, in a borrowing hydrogen cascade starting from racemic allylic alcohols, one of the enantiomers could be kinetically resolved, while the other enantiomer could be purposely converted to various targeted products, including α,ß-unsaturated ketones, ß-functionalized ketones and γ-functionalized alcohols. By employing a robust Ru-catalyst, both kinetic resolution and asymmetric induction were achieved with remarkable levels of efficiency and enantioselectivity. Density functional theory (DFT) calculations suggest that corresponding catalyst-substrate π-π interactions are pivotal to realize the observed stereochemical diversity.

Highly Efficient Kinetic Resolution of Aryl-Alkenyl Alcohols by Ru-Catalyzed Hydrogen Transfer.

No matter through asymmetric reduction of ketones or kinetic resolution of secondary alcohols, enantioselective synthesis of the corresponding secondary alcohols is challenging when the two groups attached to the prochiral or chiral centers are spatially or electronically similar. For examples, dialkyl (sp3 vs. sp3), diaryl (sp2 vs. sp2), and aryl-alkenyl (sp2 vs. sp2) alcohols are difficult to produce with high enantioselectivities. By exploiting our recently developed Ru-catalysts of minimal stereogenicity, we reported herein a highly efficient kinetic resolution of aryl-alkenyl alcohols through hydrogen transfer. This method enabled such versatile chiral building blocks for organic synthesis as allylic alcohols, to be readily accessed with excellent enantiomeric excesses at practically useful conversions.

Noni (Morinda citrifolia L.) Fruit Polysaccharides Regulated IBD Mice Via Targeting Gut Microbiota: Association of JNK/ERK/NF-κB Signaling Pathways.

Inflammatory bowel disease (IBD) is a disease characterized by intestinal inflammation with immune dysregulation and intestinal microecological imbalance. In a dextran sulfate sodium salt (DSS)-induced IBD mouse model, noni (Morinda citrifolia L.) fruit polysaccharides (NFP) with homogalacturonan and rhamnogalacturonan-I domain decreased the concentration of serum LPS, TNF-α, and IL-17 by 84, 42, and 65%, respectively. It was abolished when intestinal microbiota were depleted by antibiotics. Sequencing analysis of gut microbiota showed an attenuated disruption of the microbial composition in the DSS+NFP group. Targeted metabolomic analysis revealed that NFP upregulated the content of acetic acid, propionic acid, and butyric acid by onefold but reduced isobutyric acid and isovaleric acid contents. NFP also inhibited JNK, ERK, and NF-κB phosphorylation of IBD mice. Taken together, the mechanism of NFP alleviating IBD is related to the intestinal microecological balance to inhibit inflammatory signaling pathways. This study provides a basis for NFP as a cheap intervention for the prevention and treatment of IBD patients.

Asymmetric Synthesis of γ-Secondary Amino Alcohols via a Borrowing-Hydrogen Cascade.

The borrowing-hydrogen (or hydrogen autotransfer) process, where the catalyst dehydrogenates a substrate and formally transfers the H atom to an unsaturated intermediate, is an atom-efficient and environmentally benign transformation. Described here is an example of an asymmetric borrowing-hydrogen cascade for the formal anti-Markovnikov hydroamination of allyl alcohols to synthesize optically enriched γ-secondary amino alcohols. By exploiting the Ru-(S)-iPrPyme catalyst with minimal stereogenicity, a cascade process including dehydrogenation, conjugate addition, and asymmetric reduction was developed. The mild conditions, functional group tolerance, and broad substrate scope (54 examples) demonstrate the synthetic practicality of the catalytic system.

Catalytic mutual multicomponent reaction: facile access to α-trifluoromethylthiolated ketones.

A multicomponent catalytic reaction between ketones, Morita-Baylis-Hillman (MBH) carbonates and trifluoromethylthiolating agents is devised for straightforwardly accessing two products, α-trifluoromethylthiolated ketones and α-methylene ß-amino esters in a one pot fashion. Particularly noteworthy is that the trifluoromethylthiolating reagent is employed as both the nitrogen and SCF3 source initiated by DABCO. This mild one pot strategy enjoys atom- and step-economic attractiveness, for direct introduction of an SCF3 group onto a variety of acyclic ketones, which have been considered as less effective and less developed substrates.

Catalytic asymmetric trifluoromethylthiolation of carbonyl compounds via a diastereo and enantioselective Cu-catalyzed tandem reaction.

Although recent progress has been made in introducing an SCF3 functionality into a variety of molecules, enantioselective trifluoromethylthiolation remains challenging, especially the α-trifluoromethylthiolation of carbonyl compounds. The present study describes a diastereo and enantioselective Cu-catalyzed tandem 1,4-addition/trifluoromethylthiolation of acyclic enones. The tandem reaction enables the asymmetric integration of the -SCF3 group to carbonyl compounds, establishing chiral tertiary α-carbon centers and affording α-SCF3-ß-substituted carbonyl compounds in 50-92% yields with up to 20 : 1 dr and 96% ee.

Rh-Catalyzed Conjugate Addition of Arylzinc Chlorides to Thiochromones: A Highly Enantioselective Pathway for Accessing Chiral Thioflavanones.

A highly efficient asymmetric synthesis of chiral thioflavanones is developed via conjugate addition of arylzinc reagents to thiochromones using Rh(COD)Cl2/(R)-3,4,5-MeO-MeOBIPHEP catalyst. This method overcomes catalyst poisoning and substrate inertness and affords a series of chiral thioflavanones (2-arylthiochroman-4-ones) in good yields (up to 91% yield) with excellent ee values (up to 97% ee). The established asymmetric synthesis paves the way for further pharmaceutical studies.

Bi(OTf)3-catalyzed addition of isocyanides to 2H-chromene acetals: an efficient pathway for accessing 2-carboxamide-2H-chromenes.

Bismuth triflate (Bi(OTf)3) is identified as an efficient catalyst for the direct addition of isocyanides to 2H-chromene acetals. The large scope of isocyanides and chromene acetals makes them suitable substrates in this catalytic system. By this synthetic strategy, a polyfunctional molecular scaffold, 2-carboxamide-2H-chromenes could be prepared efficiently in one step up to 95% yield. In addition, this efficient and practical protocol proceeded smoothly in the gram scale even when the catalytic loading was reduced to 2 mol%.

Chemoselective and repetitive intermolecular cross-acyloin condensation reactions between a variety of aromatic and aliphatic aldehydes using a robust N-heterocyclic carbene catalyst.

We found that chemoselectivity of the crossed acyloin product is controlled by the adjustment of the aromatic aldehyde/aliphatic aldehyde ratio. Moreover, we observed the persistent catalytic activity of the homogeneous NHC catalyst in a solution due to NHC catalyst robustness.

N-heterocyclic carbene-catalysed intermolecular Stetter reactions of acetaldehyde.

A facile method for the intermolecular Stetter reaction of various Michael acceptors with acetaldehyde as a biomimetic acylanion source was realized using N-heterocyclic carbene catalysis. This catalytic system has also been applied to the enantioselective Stetter reaction and resulted in moderate to good enantioselectivities for the corresponding Stetter products.

Switching regioselectivity in crossed acyloin condensations between aromatic aldehydes and acetaldehyde by altering N-heterocyclic carbene catalysts.

An unprecedented high level of regioselectivities (up to 96%) in the intermolecular crossed acyloin condensations of various aromatic aldehydes with acetaldehyde was realized by an appropriate choice of N-heterocyclic carbene catalysts.