Single-arm clinical trials: design, ethics, principles.

Although randomised controlled trials are considered the gold standard in clinical research, they are not always feasible due to limitations in the study population, challenges in obtaining evidence, high costs and ethical considerations. As a result, single-arm trial designs have emerged as one of the methods to address these issues. Single-arm trials are commonly applied to study advanced-stage cancer, rare diseases, emerging infectious diseases, new treatment methods and medical devices. Single-arm trials have certain ethical advantages over randomised controlled trials, such as providing equitable treatment, respecting patient preferences, addressing rare diseases and timely management of adverse events. While single-arm trials do not adhere to the principles of randomisation and blinding in terms of scientific rigour, they still incorporate principles of control, balance and replication, making the design scientifically reasonable. Compared with randomised controlled trials, single-arm trials require fewer sample sizes and have shorter trial durations, which can help save costs. Compared with cohort studies, single-arm trials involve intervention measures and reduce external interference, resulting in higher levels of evidence. However, single-arm trials also have limitations. Without a parallel control group, there may be biases in interpreting the results. In addition, single-arm trials cannot meet the requirements of randomisation and blinding, thereby limiting their evidence capacity compared with randomised controlled trials. Therefore, researchers consider using single-arm trials as a trial design method only when randomised controlled trials are not feasible.

From sea to sea: Edible, hydrostable, and degradable straws based on seaweed-derived insoluble cellulose fibers and soluble polysaccharides.

The widespread use of disposable plastic straws has caused a long-lasting environmental problem. Potential alternatives for plastic straws are far from satisfactory due to the low utility, poor water stability, and non-ideal natural degradability. In this work, an edible, hydrostable, and degradable straw was developed from the economically significant seaweed. Seaweed-derived insoluble cellulose fibers were used as the building block of the straw, and the soluble polysaccharide extracts were explored as the natural glue through the chelation with Ca2+. Repeated freeze-thawing was introduced to strengthen the molecular interactions, which further improved its mechanical stability and hydrostability. The straw exhibited remarkable natural degradability in open environments, particularly in marine-mimicking conditions. By incorporating pH-sensitive food pigments, the straws could indicate acid-base property of a beverage or even discriminate the freshness of milk. The versatile seaweed-derived straw adhered to the biocycle concept of "from sea to sea" to alleviate the burden of white pollution on oceans.

Sinomenine regulates the cholinergic anti-inflammatory pathway to inhibit TLR4/NF-κB pathway and protect the homeostasis in brain and gut in scopolamine-induced Alzheimer's disease mice.

Sinomenine (SIN), an alkaloid extracted from the Chinese herbal medicine Sinomenium acutum, has great potential in anti-inflammatory, immune regulation, analgesic and sedative, and is already a clinical drug for the treatment of rheumatoid arthritis in China. Our previous studies show SIN inhibits inflammation by regulating ɑ7nAChR, a key receptor of cholinergic anti-inflammatory pathway (CAP), which plays an important role in regulating peripheral and central nervous system inflammation. Growing evidence supports the cholinergic dysregulation and inflammatory responses play the key role in the pathogenesis of AD. The intervention effects of SIN on AD by regulating CAP and homeostasis in brain and gut were analyzed for the first time in the present study using scopolamine-induced AD model mice. Behavioral tests were used to assess the cognitive performance. The neurons loss, cholinergic function, inflammation responses, biological barrier function in the mouse brain and intestinal tissues were evaluated through a variety of techniques, and the gut microbiota was detected using 16SrRNA sequencing. The results showed that SIN significantly inhibited the cognitive decline, dysregulation of cholinergic system, peripheral and central inflammation, biological barrier damage as well as intestinal flora disturbance caused by SCOP in mice. More importantly, SIN effectively regulated CAP to suppress the activation of TLR4/NF-κB and protect the homeostasis in brain and gut to alleviate cognitive impairment.

Levistilide A ameliorates neuroinflammation via inhibiting JAK2/STAT3 signaling for neuroprotection and cognitive improvement in scopolamine-induced Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with cognitive impairment and dementia, which has become a major public health problem. There are no effective therapeutic agents used to treat AD in clinic for the extremely complex pathogenesis. Here we identify Levistilide A (LA), one of the major active natural terpene lactone constituents from Chinese herbal medicine Angelicae sinensis and Chuanxiong Rhizoma, as a potent neuroinflammation inhibitor for neuroprotection and cognitive improvement of AD. We show that LA suppresses neuronal apoptosis, restores cholinergic system function, and lowers neuroinflammation in vivo to improve scopolamine (SCOP)-induced learning and memory deficits. In addition, LA inhibits the release of IL-1ß, IL-6 and TNF-α, while increasing the production of IL-4 and IL-10 for anti-inflammatory effects in LPS or Aß-induced BV2 and HMC3 cells. Furthermore, the conditioned medium (CM) from LA-treated BV2 or HMC3 cells enhances the viability of SH-SY5Y and HT-22 cells, and LA reverses M1 to M2 phenotype transformation of BV2 and HMC3 cells accompanied by the inhibited Iba-1 expression and mRNA level of IL-1ß, IL-6, TNF-α and NOS2, and the increased expression of ARG1, CD206 and CD163. Mechanistically, we analyze JAK2/STAT3 signaling as possible targets of LA using network pharmacology approaches, and further experimentally validate that LA inhibits the phosphorylation of JAK2 and STAT3, and STAT3 expression within nucleus both in vitro and in vivo. Collectively, we identify LA as a potential neuroinflammation inhibitor for neuroprotection and cognitive improvement, which is expected to be a candidate for AD therapy.

Synthesis of plant-derived cholesterol from bisnoralcohol.

Currently, the market demand of the non-animal-derived cholesterol is increasing. A novel synthetic route of producing cholesterol was developed through multiple reactions from plant-sourced and commercially available bisnoralcohol (BA). The key reaction conditions, including solvents, reaction temperatures, bases and reducing agents of the route were investigated and optimized. In this straightforward synthetic pathway of cholesterol, most of the reaction steps possess high conversions with average yields of 94%, and the overall yield is up to 74% (5 steps) from the BA. The epicholesterol and were also synthesized. This promising route offers economical and efficient strategies for potential large-scale production of plant-derived cholesterol.