Microbes mediated immunogenic cell death in cancer immunotherapy.

Immunogenic cell death (ICD) is one of the 12 distinct cell death forms, which can trigger immune system to fight against cancer cells. During ICD, a number of cellular changes occur that can stimulate an immune response, including the release of molecules called damage-associated molecular patterns (DAMPs), signaling to immune cells to recognize and attack cancer cells. By virtue of their pivotal role in immune surveillance, ICD-based drug development has been a new approach to explore novel therapeutic combinations and personalized strategies in cancer therapy. Several small molecules and microbes can induce ICD-relevant signals and cause cancer cell death. In this review, we highlighted the role of microbe-mediate ICD in cancer immunotherapy and described the mechanisms through which microbes might serve as ICD inducers in cancer treatment. We also discussed current attempts to combine microbes with chemotherapy regimens or immune checkpoint inhibitors (ICIs) in the treatment of cancer patients. We surmise that manipulation of microbes may guide personalized therapeutic interventions to facilitate anticancer immune response.

Harnessing natural product polysaccharides against lung cancer and revisit its novel mechanism.

The incidence and mortality of lung cancer are on the rise worldwide. However, the benefit of clinical treatment in lung cancer is limited. Owning to important sources of drug development, natural products have received constant attention around the world. Main ingredient polysaccharides in natural products have been found to have various activities in pharmacological research. In recent years, more and more scientists are looking for the effects and mechanisms of different natural product polysaccharides on lung cancer. In this review, we focus on the following aspects: First, natural product polysaccharides have been discovered to directly suppress the growth of lung cancer cells, which can be effective in limiting tumor progression. Additionally, polysaccharides have been considered to enhance immune function, which can play a pivotal role in fighting lung cancer. Lastly, polysaccharides can improve the efficacy of drugs in lung cancer treatment by regulating the gut microbiota. Overall, the research of natural product polysaccharides in the treatment of lung cancer is a promising area that has the potential to lead to new clinical treatments. With better understanding, natural product polysaccharides have the potential to become important components of future lung cancer treatments.

Design, synthesis and bioactivity evaluation of the combination of evodiamine and erlotinib linked by indolequinone.

Compared with single-targeted therapy, the design and synthesis of heterozygous molecules is still a significant challenge for the discovery of antitumor drugs. Quinone oxidoreductase-1 (NQO1) is a potential target for selective cancer therapy due to its overexpression in many cancer cells and its unique bioredox properties. Based on the principle of combinatorial drug design, we successfully synthesized a new hybrid molecules 13 with an indolequinone structure. We found that the synthesized compounds exhibited much higher cytotoxicity against the tested cancer cells than free drugs. Further mechanism studies confirmed that compound 13 induced cell apoptosis was achieved by regulating p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase.

Neuroprotection by tetramethylpyrazine and its synthesized analogues for central nervous system diseases: a review.

BACKGROUND: Due to the global increase in aging populations and changes in modern lifestyles, the prevalence of neurodegenerative diseases, cerebrovascular disorders, neuropsychiatrcic conditions, and related ailments is rising, placing an increasing burden on the global public health system. MATERIALS AND METHODS: All studies on tetramethylpyrazine (TMP) and its derivatives were obtained from reputable sources such as PubMed, Elsevier, Library Genesis, and Google Scholar. Comprehensive data on TMP and its derivatives was meticulously compiled. RESULTS: This comprehensive analysis explains the neuroprotective effects demonstrated by TMP and its derivatives in diseases of the central nervous system. These compounds exert their influence on various targets and signaling pathways, playing crucial roles in the development of various central nervous system diseases. Their multifaceted mechanisms include inhibiting oxidative damage, inflammation, cell apoptosis, calcium overload, glutamate excitotoxicity, and acetylcholinesterase activity. CONCLUSION: This review provides a brief summary of the most recent advancements in research on TMP and its derivatives in the context of central nervous system diseases. It involves synthesizing analogs of TMP and evaluating their effectiveness in models of central nervous system diseases. The ultimate goal is to facilitate the practical application of TMP and its derivatives in the future treatment of central nervous system diseases.

[Research progress in chemical constituents and pigment extraction process of Carthami Flos].

Carthami Flos(flowers of Carthamus tinctorius) with the effects of activating blood, dredging meridians, dissipating stasis, and relieving pain is one of the commonly used traditional Chinese medicines for promoting blood circulation and resolving stasis in clinical practice. So far, more than 210 compounds in Carthami Flos have been isolated and reported, including quinochalcones(safflower yellow pigments and red pigments), flavonoids, spermidines, alkaloids, polyacetylenes, and organic acids. Safflower yellow pigments, as the main water-soluble active components of Carthami Flos, is commonly obtained by the water extraction method, while red pigments are commonly obtained by the alkali extraction and acid precipitation method. In recent years, natural deep eutectic solvents as green solvents have demonstrated promising application prospects in the extraction and separation of pigments from Carthami Flos. This review systematically summarizes the chemical constituents of Carthami Flos and analyzes the extraction process of pigment components from Carthami Flos, aiming to provide a reference for further utilization of Carthami Flos resources.

Drug repurposing for COVID-19: could vitamin C combined with glycyrrhizic acid be at play by the findings of Li et al.'s database-based network pharmacology analysis?

The outbreak and pandemic of SARS-CoV-2 in 2019 has caused a severe public health burden and will challenge global health for the future. The discovery and mechanistic investigation of drugs against Coronavirus disease 2019 (COVID-19) is in deadly demand. The paper published by Li and colleagues proposed the hypothesis that vitamin C combined with glycyrrhizic acid in treating COVID-19 and its mechanistic investigation was performed by a database-based network pharmacology. In this letter, we present critical comments on the limitations and insufficiencies involved, from both the perspective of network pharmacology and current evidence on COVID-19.

Carotid Siphon Calcification Predicts the Symptomatic Progression in Branch Artery Disease With Intracranial Artery Stenosis-Brief Report.

BACKGROUND: Arterial calcification in the aortic arch, carotid bifurcation, or siphon on computed tomography was associated with cardiovascular disease. The association between arterial calcification prevalence and progression of branch atheromatous disease (BAD) in intracranial artery atherosclerosis was little investigated. METHODS: This study included 310 patients with ischemic stroke from one stroke center. Patients were divided into BAD (110) and non-BAD groups (200). Baseline characteristics, lipids, and arterial calcification were measured. The primary outcome was the prevalence of arterial calcification in BAD progression, and the secondary outcome was the prevalence of calcification in arterial stenosis. The association or correlation among calcification prevalence, lipid markers, and BAD progression was analyzed using logistic regression, receiver operating characteristic curve, and linear regression. RESULTS: Our study found that carotid siphon calcification on computed angiography was more prevalent (P=0.01) in patients with BAD and also more prevalent (P<0.001) in intracranial artery stenosis, and its computed tomography values could independently predict the symptomatic progression (P=0.01). Furthermore, a strong linear correlation between oxidized lipid and calcification density was found (beta=-0.73, P=0.0048) in patients with BAD, a subtype (B-type) of intracranial arterial atherosclerotic disease. CONCLUSIONS: We found that carotid siphon calcification was associated with BAD and its computed tomography values could predict the symptomatic progression in patients with intracranial arterial atherosclerotic disease and BAD, indicating the important role of carotid calcification in B-type intracranial arterial atherosclerotic disease. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1800018315.

Identification of LDLR mutation in cerebral venous sinus thrombosis co-existing with dural arteriovenous fistulas: a case report.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is typically associated with a prothrombotic state of the blood, with its causative factors varying widely. Prior research has not reported the simultaneous occurrence of CVST and dural arteriovenous fistulas (DAVFs) as potentially resulting from genetic mutations. In this case report, we introduce a unique occurrence wherein a patient with a heterozygous mutation of the low-density lipoprotein receptor (LDLR) gene presented with CVST in conjunction with DAVFs. CASE: Presentation: A male patient, aged 51, sought treatment at our facility due to a consistent decline in cognitive functions accompanied by recurrent headaches. Comprehensive evaluations were administered, including neurological examinations, laboratory tests, magnetic resonance imaging, digital subtraction angiography, and whole exome sequencing. Digital subtraction angiography identified DAVFs in the patient's right sigmoid sinus and an occlusion within the left transverse sinus. The whole exome sequencing of blood samples pinpointed a heterozygous mutation in the LDLR gene (NM_000527:exon12:c.C1747T:p.H583Y). Following the confirmed diagnosis of CVST and DAVFs, the patient underwent anticoagulant therapy combined with endovascular procedures - these comprised embolization of the arteriovenous fistula in the right sigmoid sinus and balloon dilation with stent implantation in the left transverse sinus. A six-month follow-up indicated a significant abatement in the patient's symptoms. CONCLUSIONS: This report marks the first documented case of an LDLR gene mutation that could be associated with the onset of CVST and DAVFs. The mutation in the LDLR gene might foster a prothrombotic environment, facilitating the gradual emergence of CVST and the subsequent genesis of DAVFs.

Reduced left hippocampal perfusion is associated with insomnia in patients with cerebral small vessel disease.

OBJECTIVES: Insomnia was associated with cerebral structural changes and Alzheimer's disease. However, associations among cerebral perfusion, insomnia with cerebral small vessel disease (CSVD), and cognitive performance were little investigated. METHODS: This cross-sectional study included 89 patients with CSVDs and white matter hyperintensities (WMHs). They were dichotomized into the normal sleep and poor sleep group, according to Pittsburgh sleep quality index (PSQI). Baseline characteristics, cognitive performance, and cerebral blood flow (CBF) were measured and compared between the two groups. The association or correlation between cerebral perfusion, cognition, and insomnia was analyzed using binary logistic regression. RESULTS: Our study found that declined MoCA score (P = .0317) was more prevalent in those with poor sleep. There was a statistical difference in the recall (P = .0342) of MMSE, the delayed recall (P = .0289) of MoCA between the two groups. Logistic regression analysis showed educational background (P < .001) and insomnia severity index (ISI) score (P = .039) were independently correlated with MoCA scores. Arterial spin labeling demonstrated that left hippocampal gray matter perfusion was significantly reduced (P = .0384) in the group with poor sleep. And, negative correlation was found between left hippocampal perfusion and PSQI scores. CONCLUSIONS: In the patients with CSVDs, insomnia severity was associated with cognitive decline. Left hippocampal gray matter perfusion was correlated with PSQI scores in CSVDs.

Design, synthesis, AML activity and molecular modeling of novel IDH2 inhibitors.

Enasidenib (AG-221) is the only approved IDH2 inhibitor, clinical study found Enasidenib have some side-effects. In this work, we synthesized series of novel s-triazine derivatives, and the in vitro and in vivo activity of anti-AML has been studied using AM7577 model. The cell activity found Ta and Th showed excellent inhibition to AM7577. We further used the HuKemia Acute Leukemia xenograft model to investigate the in vivo efficacy of compounds Ta and Th, compared with AG-221, although Ta and Th can't reduce the 2-HG level obviously, those two compounds can prolong the survival of rats. The research can expand the structure of novel IDH2 inhibitors and provide useful information for further research of novel AML drugs.

A Novel Method for Treating Distal Radius Diaphyseal Metaphyseal Junction Fracture in Children.

BACKGROUND The treatment of distal radius diaphyseal metaphyseal junction (DMJ) fracture in children is a clinical problem; several treatments are available, but none are very effective. Therefore, this study aimed to report a novel method for treating this fracture using limited open reduction and transepiphyseal intramedullary fixation with Kirschner wire. MATERIAL AND METHODS From January 2018 to December 2019, a total of 15 children (13 boys and 2 girls) with distal radius DMJ fractures with a mean age of 10 years (range: 6-14 years) were included in the study. The operation time, incision length, and X-ray radiation exposure were precisely recorded. All children were followed up regularly. At the final follow-up, clinical outcomes were evaluated according to Price criteria, and complications were recorded. RESULTS The mean operation time of the 15 children was 21.4 min, and the mean incision length was 1.9 cm. The intraoperative X-ray was performed 3.7 times on average. The mean radiographic union of fracture was 4.7 weeks, and the mean time to remove the Kirschner wire was 4.8 weeks for radial instrumentation and 4.7 months for ulnar instrumentation. According to the Price grading evaluation system, clinical outcome was excellent in 14 cases and good in 1 case. Moreover, there were no major complications related to loss of reduction, malunion, nonunion, and physeal arrest of the distal radius. CONCLUSIONS Limited open reduction and transepiphyseal intramedullary fixation with Kirschner wire are effective for treating distal radius DMJ fracture in children, which has the advantages of simple surgical procedures, short operation time, small incision, and less radiation exposure, making it an excellent choice for treating this fracture.

The association between serum folate and gestational diabetes mellitus: a large retrospective cohort study in Chinese population.

OBJECTIVE: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. DESIGN: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage-response relationship between serum folate and the risk of GDM. SETTING: A sigle, urban hospital in Shanghai, China. PARTICIPANTS: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. RESULTS: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs). CONCLUSIONS: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.

The serum lipidomics reveal the action mechanism of Danggui-Yimucao herbal pair in abortion mice.

Medical abortion is a common medical procedure that women choose to terminate an unwanted pregnancy, but it often brings post-abortion complications. Danggui (Angelica sinensis Radix)-Yimucao (Leonuri Herba), as a herbal pair (DY) in clinical prescriptions of traditional Chinese medicine, is often used in the treatment of gynecological diseases and has the traditional functions of tonifying the blood, promoting blood circulation, removing blood stasis and regulating menstruation. In this study, serum lipidomics were adopted to dissect the mechanism of DY in promoting recovery after medical abortion. A total of 152 differential metabolites were screened by lipidomics. All metabolites were imported into MetaboAnalyst for analysis, and finally key metabolic pathways such as glycerophospholipid metabolism, linoleic acid metabolism and pentose and glucuronate interconversions were enriched. Our results indicated that metabolic disorders in abortion mice were alleviated by DY through glycerophospholipid metabolism, while prostaglandin and leukotriene metabolites might be the key targets of DY to promote post-abortion recovery.

Optimal time window for minimally invasive surgery in treating spontaneous intracerebral hemorrhage in the basal ganglia region: a multicenter and retrospective study.

BACKGROUND: The current treatment spontaneous intracerebral hemorrhage (sICH) is limited. AIM: To determine the optimal time window for minimally invasive surgery in patients with sICH. MATERIALS AND METHODS: sICH patients with a hematoma volume of 30-80 mL in the basal ganglia region were included in our study. A total of 357 patients were divided into groups according to different operative times from ICH onset (group 1: 0-6 h, group 2: 6-12 h, group 3: >12 h) and hematoma volumes (30-50 mL and >50 mL). All patients were followed-up for three months' post-operation, and their clinical outcomes were compared. RESULTS: In the three groups of patients with hematoma volumes of 30-50 mL, the rebleeding and mortality rate were higher in group 1 than groups 2 and 3 (p < .05). The activities of daily living evaluated by Barthel Index (BI) three months' post-operation was significantly lower in group 3 than other groups (p < .05) and group 2 had the highest proportion of good outcomes. Among the patients with the hematoma volumes of 50-80 mL, the rebleeding risk was higher in group 1 than groups 2 and 3 (p < .05). However, there were no significant differences in mortality rates among these three groups. Moreover, group 1 had significantly higher BI than groups 2 and 3 (p < .05). CONCLUSIONS: Minimally invasive surgery is safe and effective in patients with sICH. 6-12 h after sICH onset is the optimal surgical window for patients with hematoma volumes of 30-50 mL, while ultra-early (≤6 h) may achieve better results in patients with hematoma volumes of >50 mL.

[Identification of quality markers of Gei Herba based on analytic hierarchy process-entropy weight method and network pharmacology].

Analytic hierarchy process(AHP)-entropy weight method(EWM) and network pharmacology were employed to identify the potential quality markers(Q-markers) of Gei Herba. According to the new concept of Q-markers in traditional Chinese medicine(TCM), the AHP-EWM was applied to quantitatively identify the Q-markers of Gei Herba. The AHP was used for the weight analysis of primary indicators(factor layer), and the EWM for the analysis of literature and experimental data of secondary indicators(control layer). In addition, network pharmacology was employed to build the "component-target-disease-efficacy" network for Gei Herba, and the components showing strong associations with the Qi-replenishing, spleen-invigorating, blood-tonifying, Yin-nourishing, lung-moistening, and phlegm-resolving effects of Gei Herba were screened out. According to the results of AHP-EWM and network pharmacology, four components, i.e., ellagic acid, gallic acid, gemin G, and gemin C, were finally identified as potential Q-markers of Gei Herba. In this study, the AHP-EWM and network pharmacology were employed to screen the Q-markers of Gei Herba, which provided ideas for the quantitative evaluation and identification of Q-markers of TCM.

Compliance of functional exercises in school-age children with limb fractures: implication for nursing countermeasures.

BACKGROUND: Functional exercises is very essential to the recovery of patients with fracture. We aimed to evaluate the compliance of functional exercises in school-age children with limb fracture, to provide evidence to the clinical management and nursing care of children with limb fracture. METHODS: School-age children with limb fractures treated in our hospital from January 1, 2020 to June 30, 2021 were selected. The characteristics and postoperative functional exercise compliance of included children were analyzed. Pearson correlation and Logistic regression analysis were conducted to analyze the influencing factors of compliance to functional exercises. RESULTS: A total of 328 children with limb fracture were included, the incidence of compliance to functional exercise was only 35.98%. Pearson correlation analysis showed that age(r = 0.707), only child of family(r = 0.537), guardians(r = 0.642) and type of temperament(r = 0.635) were correlated with compliance to functional exercises in school-age children with limb fractures (all p < 0.05). Logistic regression analysis indicated that age ≤ 10y (OR2.913, 95%CI2.091 ~ 3.611), only child of family (OR2.006, 95%CI1.683 ~ 2.558), guarded by grandparents (OR1.512, 95%CI1.201 ~ 2.118), non-easy-going temperament (OR4.127, 95%CI3.811 ~ 4.902) were the influencing factors of non-compliance to functional exercises in children with limb fracture (all p < 0.05). CONCLUSIONS: School-age children have poor compliance with functional exercises after limb fractures, and there are many influencing factors. For children with those risks, health care providers should actively intervene in nursing to improve children's exercise compliance and the rehabilitation effect.

Evodiamine and Rutaecarpine as Potential Anticancer Compounds: A Combined Computational Study.

Evodiamine (EVO) and rutaecarpine (RUT) are the main active compounds of the traditional Chinese medicinal herb Evodia rutaecarpa. Here, we fully optimized the molecular geometries of EVO and RUT at the B3LYP/6-311++G (d, p) level of density functional theory. The natural population analysis (NPA) charges, frontier molecular orbitals, molecular electrostatic potentials, and the chemical reactivity descriptors for EVO and RUT were also investigated. Furthermore, molecular docking, molecular dynamics simulations, and the analysis of the binding free energies of EVO and RUT were carried out against the anticancer target topoisomerase 1 (TOP1) to clarify their anticancer mechanisms. The docking results indicated that they could inhibit TOP1 by intercalating into the cleaved DNA-binding site to form a TOP1−DNA−ligand ternary complex, suggesting that they may be potential TOP1 inhibitors. Molecular dynamics (MD) simulations evaluated the binding stability of the TOP1−DNA−ligand ternary complex. The calculation of binding free energy showed that the binding ability of EVO with TOP1 was stronger than that of RUT. These results elucidated the structure−activity relationship and the antitumor mechanism of EVO and RUT at the molecular level. It is suggested that EVO and RUT may be potential compounds for the development of new anticancer drugs.

[Research on Q-markers of Polygoni Perfoliati Herba based on analytic hierarchy process-entropy weight method and fingerprints].

The potential quality markers(Q-markers) of Polygoni Perfoliati Herba were studied based on analytic hierarchy process(AHP)-entropy weight method(EWM), network pharmacology, and spectrum-effect relationship analysis. The AHP-EWM was used for quantitative identification of the Q-markers. To be specific, AHP was applied for the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM for the analysis of the second-level indexes supported by literature and experimental data. Based on literature and network pharmacology, the validity analysis was to study the component-target-disease-efficacy network, and select the components with the strongest correlation with the efficacy of clearing heat and removing toxin, diuresis and alleviating edema, and relieving cough. For the testability analysis, the high performance liquid chromatography(HPLC) and literature research were used to determine the 10 components in Polygoni Perfoliati Herba, and the fingerprints of Polygoni Perfoliati Herba were established at the same time. The specificity analysis was based on the statistics of the number of plants in which the components existed. Thereby, the 11 compounds: quercetin, oleanolic acid, ellagic acid, gallic acid, kaempferol, rutin, esculetin, quercetin-3-O-glucuronide, ursolic acid, protocatechuic acid, and ferulic acid, were identified as potential Q-markers. The 11 compounds were identified to have high anti-inflammatory activity, indicating that the 11 Q-markers may be the functional material basis. The result in this study is expected to serve as a reference for the quality control of Polygoni Perfoliati Herba.

[Quantitative identification of Q-markers of Euphorbiae Humifusae Herba based on AHP-CRITIC comprehensive weighting method].

This study investigated the quality markers(Q-markers) of Euphorbiae Humifusae Herba based on the analytic hierarchy process(AHP)-criteria importance through intercriteria correlation(CRITIC) comprehensive weighting method. The Q-markers evaluation system was constructed based on the AHP-CRITIC comprehensive weighting method with quantitative identification of Q-markers of Euphorbiae Humifusae Herba as the target layer. The index weights of the factor layer and the control layer were integrated based on the weights of three indicators(effectiveness, testability, and specificity) in the factor layer calculated by the AHP method and weights of eight indicators(anti-inflammatory inhibitory rate, coagulation shortening rate, anti-cancer inhibition rate, component degree value, component test batch, component average content, content variation coefficient, and number of medicinal materials retrieved according to components) in the control layer calculated by the CRITIC method. The comprehensive score of the chemical components of Euphorbiae Humifusae Herba was weighted and ranked to identify the Q-markers of Euphorbiae Humifusae Herba. In terms of comprehensive scores, top 10 potential Q-markers of Euphorbiae Humifusae Herba were ranked as cynaroside > quercetin > gallic acid > apigenin > luteolin > apigenin-7-O-glucoside > quercetin-7-O-glucoside > ellagic acid > astragalin > ethyl gallate. This study provides a reference for the quality control of Euphorbiae Humifusae Herba and a methodological reference for the quantitative identification of Q-markers of Chinese medicine.

Rhodium-Catalyzed ON-OFF Switchable Hydrogenation Using a Molecular Shuttle Based on a [2]Rotaxane with a Phosphine Ligand.

A novel pH-responsive molecular shuttle based on a [2]rotaxane with a phosphine ligand has been designed and synthesized. In the rhodium-catalyzed hydrogenation of α,ß-dehydroamino acid esters and aryl enamides, ON/OFF-switchable catalysis was accomplished with high ON/OFF ratios by adjusting the movements of the rotaxane wheels located at the catalyst terminals with acid/base. Mechanistic studies using NMR spectroscopy and quasi in situ X-ray photoelectron spectroscopy revealed that RhIII -hydride species are possibly formed in a H2 atmosphere when the catalyst is in the OFF state. During the reaction, a heterolytic activation of dihydrogen occurs by the interlocked rotaxane dibenzylamine and RhI catalytic center acting as a frustrated Lewis pair. Subsequent homolytic splitting of dihydrogen with the newly formed RhI -hydride species generates RhIII -hydride species. These findings show that a substrate-selective hydrogenation can be achieved by using the OFF-state catalyst.