We found that AR addition stimulated phytoplankton growth obviously, as indicated by chlorophyll a (Chl a) in surface incubations, and had stimulatory or no effects in SCM incubations, which was related to nutrient statuses in seawater. The high ratio of nitrogen (N) to phosphorus (P) in the AR treatments demonstrated that P became the primary limiting nutrient. The alkaline phosphatase activity (APA), which can reflect the rate at which dissolved organic P (DOP) is converted into dissolved inorganic P, was 1.3–75.5 times higher in the AR treatments than in the control, suggesting that AR addition increased P bioavailability in the incubated seawater. Dinoflagellates with the capacity to utilize DOP showed the dominant growth in the AR treatments, corresponding to the shift in phytoplankton size structure toward larger cells. Surprisingly, we found that nanosized (2–20 μm) and picosized (0.2–2 μm) Chl a concentrations in UFS were generally higher than those in FS. The APA in UFS was at least 1.6 times higher than in FS and was proportional to the contribution of microsized cells to the total Chl a, suggesting that microsized cells play an important role in the increase in APA, which contributes to the growth of nanosized and picosized phytoplankton. Current work provides new insight into the increase of P bioavailability induced by atmospheric deposition and resultant ecological effect in coastal waters.Atmospheric deposition can supply nutrients to induce varying responses of phytoplankton of different sizes in the upper ocean. Here, we collected surface and subsurface chlorophyll  Atmospheric deposition can supply a considerable amount of nutrients, including macronutrients such as nitrogen (N) and phosphorus (P), and micronutrients such as iron (Fe) and zinc (Zn), to the ocean , and affThe impact of atmospheric deposition on primary productivity is generally associated with the substantial supply of N and/or Fe nutrients, whereas few studies focus on P due to its negligible supply relative to N and Fe . Althouga maximum (SCM) (The Yellow Sea (YS) and ECS adjacent to the East Asian continent are marginal seas of the northwestern Pacific Ocean and are obviously influenced by anthropogenic air pollutants from the surrounding continent . A serieum (SCM) . In contIn this study, we carried out three onboard incubation experiments enriched with AR using surface and SCM seawaters in the YS and ECS. The unfiltered and filtered (through 20-μm membrane) seawaters were used to illustrate the effects of microsized (20–200 μm) phytoplankton on the growth and nutrient uptake of nanosized (2–20 μm) and picosized ones. Based on this, our study intended to (1) reveal the difference in phytoplankton response to AR addition in surface and SCM seawaters; (2) identify the main factor of AR addition that affects the growth and community structure succession of phytoplankton; and (3) explore the interaction between different sized phytoplankton under the effects of AR addition.–3, indicating that the air quality is moderate. The detailed air quality conditions are shown in The AR samples used for incubation experiments were collected with a cellulose acetate filter membrane (Whatman 41) on the Laoshan campus of Ocean University of China  on 30 June 2019. During the sampling period, the AQI was 57–83 μg mSur and UiSCM, respectively, and i refers to the site number, i.e., 1/2/3.In the summer of 2019, three onboard microcosm experiments were conducted during the cruise of R/V Beidou in the YS and the northern part of the ECS . The ini–1) at U2, indicating that the added amount of AR contains 1 μmol N L–1; (3) high AR addition, 1.7 μmol N L–1at U3, and 2 μmol N L–1 at U1. AR sample was first ultrasonically extracted in deionized water at 0°C for 1 h, and the leaching solution including particles was added to the incubation bottles directly  divided by an averaged mixed layer of 30 m  control, no AR addition; (2) low AR addition, the added amount of AR was expressed in the unit of N  was transferred uniformly into three 2-L bottles to continue the cultivation. The incubations unfiltered with 20-μm sieves were defined as the unfiltered seawater  20-L polycarbonate incubation bottles. These incubation bottles were placed into three microcosm devices filled with continually updated surface seawater to keep the incubation system temperature relatively stable . To expla concentration was obtained by summing three size-fractionated Chl a concentrations.Approximately 150 ml of seawater from incubated bottles was sampled at ∼07:00 a.m. every day during the incubations. The sampled seawater was subsequently filtered through 20-, 2-, and 0.2-μm filters, to obtain microsized, nanosized, and picosized cells. After 20–24 h of extraction by 90% acetone in darkness at –20°C, the pigments collected by different filters were measured using a Trilogy fluorometer (Turner Designs). The total Chl 3–, NO2–, NH4+, Si(OH)4, and PO43–. In addition, ∼200 ml of incubated seawater (sampled every day) was filtered through acid-washed cellulose acetate membranes into 125-ml acid-washed high-density polyethylene bottles (prerinsed with the filtrates three times). The water samples were frozen at -20°C immediately prior to the determination of NO3– + NO2–, PO43–, and Si(OH)4 in the university laboratory. All nutrient samples were measured with a QuAAtro continuous-flow analyzer . The detection limits for NH4+, NO3–,NO2–, PO43–, and Si(OH)4 were 0.04, 0.02, 0.005, 0.01, and 0.03 μmol L–1, respectively. For convenience, NO3– + NO2– is abbreviated to N + N.An ultrasonic method was used to leach nutrients in AR samples. Briefly, AR samples were ultrasonically extracted in deionized water at 0°C for 1 h. The leaching solution was then filtered through a 0.45-μm polyethersulfone syringe filter . The fil2 cellulose acetate filter was put into the Teflon high pressure vial, with 2 ml of 69% HNO3 and 0.5 ml of 40% HF. After digestion at 180°C for 48 h, the solution was evaporated at 160°C, the residue was dissolved with 2% HNO3 and diluted to 50 ml for determination.The concentrations of total trace metals were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) . The 8-cAbout 45 ml of seawater was sampled from the incubated bottles and mixed with 0.5 ml of fluorogenic substrate 4-methylumbelliferone phosphate (MUF-P) as the mixed substrate. After the addition of the mixed borax-sodium carbonate buffer solution (pH = ∼11) and the mixed substrate to the sample tube, the fluorogenic substrate MUF-P hydrolyzed by AP was converted into equimolar phosphate group and 4-methylumbelliferone (MUF). The fluorescence value of MUF was measured and recorded by a Trilogy fluorometer (Turner Designs) at 0, 0.5, and 1 h . The slo1 . Filters were stored immediately in liquid nitrogen until DNA extraction and high-throughput sequencing . The V4 hypervariable region was selected as the target region of the 18S rDNA . The pri1  was useda concentration between the control and treatments 4 were 0.19, 0.01, and 2.85 μmol L–1, respectively. APA was 35.3 nmol (L h)–1 in the original seawater, consistent with the reported value of ∼35 nmol (L h)–1 in this region  contributed to the most of the total Chl a, followed by nanosized cells (18%) and microsized cells (9%) (At U1s region . The totlls (9%) . ChloropSur, U3Sur and U3SCM, low concentrations of N + N and PO43– were observed, i.e., 0.08-0.11 and ∼0.01 μmol L–1, respectively. The APA was less than 18.4 nmol (L h)–1, and the total Chl a concentration (0.55-0.62 μg L–1) was more than 1.4 times higher than that at U1Sur. Picosized Chl a contributed to the most of the total Chl a (47-65%), and the contribution of microsized Chl a was less than 15%. Dinophyceae dominated the communities with a relative abundance of ≥85% 4. The APA at U1SCM and U2SCM [3.4-3.7 nmol (L h)–1] was of the same orders of magnitude as those of U2Sur and U3SCM. The total Chl a concentration (≥0.95 μg L–1) was more than 1.7 times higher than that of U1Sur and U2Sur. Picosized phytoplankton (52-62%) were the primary contributors to the total Chl a. Dinophyceae dominated the communities with a relative abundance of ≥89% 4 in the AR, the changes in the concentrations of PO43– and Si(OH)4 in AR-amended seawater were slight at all sites.The N:P ratio after AR addition increased from 11:1-20:1 to 44:1-54:1 at all sites in the surface incubated seawater and at U3Sur and U3SCM, the concentrations of N + N did not change significantly in the control and AR treatments 4 in the control and AR treatments was less than 13% at U1-3Sur and U3SCM. At U1SCM and U2SCM, the concentrations of N + N and PO43– decreased gradually by more than 85% in the control and AR treatments relative to the original values. The concentrations of Si(OH)4 decreased sharply in the control (>28%) and AR treatments (>69%) on days 3-5 at both sites 4 between FS and UFS in the control and AR treatments at U1-3Sur and U3SCM. In the FS at U1SCM and U2SCM, the consumption of N + N and Si(OH)4 in AR treatments was lower than that in the UFS at the end of the incubations  than that in the FS . A similar pattern in the size shift toward larger cells also occurred at U2Sur and U3Sur, although picosized cells always dominated the contribution to total Chl a  on day 5. At U3SCM, the dominant contributor was always picosized phytoplankton during the incubations  at U3SCM was lower than that in UFS (0.25 μg L–1) on day 6. In contrast, at U1SCM, nanosized and picosized Chl a concentrations in FS (4.72 and 0.36 μg L–1) were higher than those in UFS (2.89 and 0.22 μg L–1) on day 5. At U2SCM, there was no significant difference in the concentrations of size-fractionated Chl a between UFS and FS  at U1Sur. Chloropicon spp. was the main component of Chloropicophyceae . The ASV richness of Dinophyceae (dinoflagellates) accounted for ≥60% of phytoplankton in the original seawater at each site. In terms of UFS, Dinophyceae dominated the phytoplankton community in the AR treatments at all sites . The domophyceae . With ARophyceae . The sucon sites .Sur and U3SCM with lower trophic status, where the concentrations of N + N, PO43–, and Si(OH)4 did not exceed 0.50, 0.02, or 3.00 μmol L–1, respectively; U1SCM and U2SCM with higher trophic status, where the concentrations of N + N, PO43–, and Si(OH)4 exceeded 1.50, 0.10, and 4.50 μmol L–1, respectively.Based on the distinct nutrient concentrations  in the original seawaters, the sites used for incubations were classified into two types: U1-3SCM, although its trophic status was similar to those in surface seawaters   . Collect43– and APA  through particle rejection behavior  can be found in the article/QW: conceptualization, investigation, methodology, data curation, formal analysis, visualization, software, and writing – original draft. CZ: conceptualization, investigation, writing – review and editing, data curation, and funding acquisition. HJ: investigation. YC and XY: writing – review and editing. HG: supervision, methodology, resources, writing – review and editing, and funding acquisition and also was responsible for ensuring that the descriptions are accurate and agreed by all authors. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


There is a trend towards the formalization of the rehabilitation process for older rehabilitants in a Challenging Rehabilitation Environment (CRE). This concept involves the comprehensive organization of care, support, and environment on rehabilitation wards. So far, literature on the principles of the CRE is scarce. This study aims to explore the perspectives regarding the CRE of healthcare professionals through a qualitative study. Therefore, between 2018 and 2020, six international and 69 Dutch professionals were interviewed in focus groups, and 180 professionals attended workshops on two Dutch congresses. Data were thematically analyzed using ATLAS.ti. Seven themes emerged regarding the rehabilitation processes: (1) rehabilitant (attention for cognitive functioning and resilience); (2) goals ; (3) exercise (increasing exercise intensity); (4) daily schedule (following the daily rhythm); (5) involving the client system ; (6) nutrition (influences rehabilitation capability); and (7) technology . Regarding organizational aspects, four main themes were identified: (1) environmental aspects (encourages exercises); (2) staff aspects (interdisciplinary team); (3) organizational aspects (implementing CRE requires a shared vision); and (4) factors outside the ward (a well-prepared discharge process). To offer effective rehabilitation, all elements of the CRE should be applied. To improve the CRE, specific interventions need to be developed and implemented. Consequently, the effectiveness and efficiency of the CRE need to be measured with validated tools. Rehabilitation involves the identification of a person’s problems, challenges, and needs. This leads to defining rehabilitation goals and subsequent interventions offered by a multidisciplinary team . PersonsA specific form of rehabilitation is geriatric rehabilitation (GR), which has recently been defined as ‘a multidimensional approach of diagnostic and therapeutic interventions, the purpose of which is to optimize functional capacity, promote activity and preserve functional reserve and social participation in older people with disabling impairments’ . RehabilIn the Netherlands, there is a trend towards having the rehabilitation process take place within the context of a challenging rehabilitation environment (CRE). A CRE is a widely accepted practice-based innovation in the Netherlands ,9,10. ItA review conducted by the authors initially identified seven main components for modelling CRE: (1) therapy time; (2) group training; (3) patient-regulated exercise; (4) family participation; (5) task-oriented training; (6) enriched environment; and (7) team dynamics .Although internationally there is a growing interest in the principles of this relatively new concept, there is no official scientific-based definition of the CRE. This results in considerable differences between rehabilitation wards in the interpretation of rehabilitation in general and the execution of a CRE specifically. Because of these differences in interpretation, the seven mentioned components are not guaranteed to cover all aspects of the CRE, and the question emerges regarding which aspects are found to be relevant by stakeholders besides the seven aspects found in the literature.To date, no evidence-based conceptualization of CRE has been developed, and empirical evidence for the added value of CRE for rehabilitants is lacking. The current study is part of the CREATE study  . In thisTo explore the perspectives of professionals on the concept of the CRE, a qualitative study consisting of focus groups and workshops was performed between September 2018 and January 2020. The primary aim of qualitative research is to gain a better understanding of a phenomenon through the experiences of those involved . As not We adhered to the consolidated criteria for reporting qualitative research (COREQ), which aim to improve the quality of reporting this type of research see  15]..15].Participants were eligible if they had recent experience in the field of (geriatric) rehabilitation and were willing to sign an informed consent form after receiving verbal and written information on the study. During the recruitment phase, we aimed at obtaining input from different professional disciplines in the broad field of rehabilitation, e.g., medical doctors, physical therapists, occupational therapists, psychologists, speech and language therapists, and nurses, as well as researchers in the field of GR.Recruitment for the focus groups was split into three target audiences: experts, (para)medics, and nursing staff. This subdivision was made to ensure that all participants were able to express their perspectives, regardless of educational or hierarchical issues.At the start of the study, we composed a list of 31 Dutch national experts in the field of (geriatric) rehabilitation. These experts were invited by email to participate and were asked to supplement the list with names of people they regarded as experts. This resulted in a list of 38 people who were invited to participate in these focus groups.Furthermore, an international focus group was established with non-Dutch members of the Special Interest Group Geriatric Rehabilitation (SIG GR) of the European Geriatric Medicine Society (EuGMS) . FourteeOrganizations affiliated with the six academic networks for elderly care in the Netherlands were approached by email with information about this study . They weWe aimed for data saturation, and after each focus group, the authors discussed whether any new topics had emerged. Inclusion stopped when all disciplines were represented in focus groups and no new topics emerged.Additionally, the study group was asked to organize four workshops concerning the theme CRE during two Dutch national congresses in the field of rehabilitation. This opportunity was used to ask the participants of these congresses to provide input on topics relevant to CRE. Visitors of these congresses were able to register for these workshops, and they were informed that their input was used for the conceptualization of CRE. Participation in the workshops was voluntary, and no personal information was collected.The aim of the focus groups was to clarify the perspectives of the participants regarding CRE. The groups were chaired by E.D. or B.B., and L.T. took field notes during the group interviews. E.D. and B.B. are both female senior nursing researchers in the field of rehabilitation. Both are experienced in qualitative research and chairing discussion groups. Physical therapist L.T. is a female PhD student with formal training in interview techniques and qualitative research and has 10 years of experience in geriatric rehabilitation.In preparation for these groups, L.T. developed a topic list  based onThe focus groups for Dutch experts were held in a meeting center centrally located in the Netherlands. The international expert group was held at the congress location of EuGMS 2019, Krakow. The focus groups for the other professionals were conducted at meeting centers and rehabilitation wards spread across the Netherlands. All focus groups took place in meeting rooms, and only the participants and researchers were present.Each focus group began with a brief introduction to the study and the topic of the focus groups, followed by the introduction of the individual participants. The participants were then asked to share their perspectives on CRE. The chair asked open-ended questions based on the topic list to keep the conversation going. To increase the internal validity, participants were also asked to share their perspectives on subjects that were not included in the topic list but which they considered important regarding CRE.On average, the duration of the focus groups was 110 min, and they were audiotaped and transcribed verbatim by L.T. Transcripts were not returned to participants for comments, but at the end of every focus group, the chair presented a verbal summary and checked its accuracy with the participants.Four 50-min workshops were held at two Dutch national congresses in the field of rehabilitation. Each workshop started with a presentation by L.T. about the results of the review on CRE . ParticiParallel to the data collection, we performed a thematic analysis to identify, analyze, and report patterns in the data ,18. For L.T. familiarized herself with the data by reading and re-reading the transcripts, after which initial themes were identified using an open-coding approach. These initial themes were checked and coded by B.B. and E.D. to determine inter-rater agreement. Differences in the coding were discussed by L.T., E.D., and B.B. until an agreement was reached. Each initial theme was described in a memo. The identified initial themes were combined into main themes with associated sub-themes. The connections and contradictions between the initial themes were described per main theme and connections between main themes were described in categories. Each main theme was assessed for data saturation by checking whether no new data emerged in the focus groups or workshops. Subsequently, the research team discussed the main themes. After an agreement was reached, each main theme was thoroughly described, and relevant quotes were identified and translated into English.Between September 2018 and October 2019, a total of 13 focus groups were conducted: one international expert group (n = 6), three national Dutch expert groups (n = 17), three (para)medics groups (n = 24), and three groups with nursing staff (n = 28). Eleven of the invited Dutch experts and eight of the invited international experts were not able to participate. Reasons for not participating were time management concerns, not being present at EuGMS congress 2019, or having the impression of not having sufficient knowledge about the subject.The workshops were held in November 2019 and January 2020. A total of 180 rehabilitation professionals participated in these workshops.Characteristics of the participants are shown in Eleven main themes with associated sub-themes emerged from the data. The main themes can be divided into two categories, namely themes involving rehabilitation processes and themes involving organizational aspects. The subdivision of the themes within the two categories is described in This category consists of seven main themes: (1) rehabilitant; (2) goals; (3) exercise; (4) daily schedule; (5) involving client system; (6) nutrition; and (7) technology.A CRE is suitable for all diagnosis groups, although the principles of CRE must be introduced to rehabilitants and their informal caregivers to stimulate self-reliance.During the rehabilitation process, attention should be paid to potential cognitive problems, sometimes pre-existent or sometimes newly emerged. One nurse practitioner stated:Especially in CVA patients, depression is quite common and very often underestimated. ... But this has to be included, because if the mood is not right, there is a very negative impact on the rehabilitation process.As an elderly care physician said, it is important to take the rehabilitant’s resilience into consideration in their day program:But 1 time 24 minutes is not the same as 24 times 1 minute. And those 24 times 1 minute is what you want in a CRE. You can also spread patients with limited abilities over the day so that they can still continue in therapy, despite their limits.In GR, it is important to work on the rehabilitant’s own goals for motivation, self-reliance and independence. Sometimes, rehabilitants need guidance from professionals or informal caregivers to describe their goals. A manager with a background as a physical therapist explained:It starts with a good talk and actually motivating the rehabilitant. Everyone is motivated for something, but maybe not for your goals.Participants miss measurement instruments validated for the GR populations to measure the success of rehabilitation. As one rehabilitation physician stated:I want to advocate defined clinimetrics. To inform [rehabilitants] properly and measure treatment success.To achieve the highest possible exercise intensity, training moments must be integrated into the daily routine. With task-oriented exercises, rehabilitants train meaningful tasks aimed at a participation level. A rehabilitation physician explained:So, the question is, how do you integrate exercise components in the daily routine. …. So, I think, this is really, let’s say, the big picture. That we have to change the climate of how we work with the people.Patient-regulated exercises can increase the exercise intensity and stimulate the rehabilitants’ independence. If group training is focused on the goals of a rehabilitant, it can increase the exercise intensity and stimulates contact with other rehabilitants. An elderly care physician said:I think group therapy can be very efficient. ... It may help when people practice in a group and you have peer support.Within a CRE, across the entire day, all activities should be focused on rehabilitation, and those activities should be stimulated.Participants are in favor of working without strict planning to be able to respond to the rhythm of the rehabilitant and stimulate interdisciplinary cooperation. As a nurse mentioned:I would prefer to have one occupational therapist and one physiotherapist on the ward structurally. Who can just help out on the ward from morning to evening, and at the same time provide therapy.The client system can be seen as fellow practitioners in the rehabilitation process, but staff must guard against overburdening the informal caregiver. One nurse and lecturer explained:I do think it’s important that the family caregiver has a place and is a natural part of the whole. I also think it’s very important that we are aware that, from the family caregiver’s perspective, there is no end to it.To be able to involve the informal caregivers in the rehabilitation, communication is a key aspect. As an elderly care physician and researcher said:What I also see a lot ... is that even for family caregivers it is often unclear what they should expect. What the approach will be and what the goal of the rehabilitation ward is. In addition to everything we have already said, I think that explaining and providing information is also an important part of the rehabilitation climate.The nutritional status of a rehabilitant partly determines their workload capacity. So, attention to a protein-rich diet with the most common products possible is important. One elderly care physician mentioned the importance of nutrition:Nutritional status is another one. Yes, it’s getting more attention now, but it has been underexposed for a very long time I think. And also the link with people sometimes just being too tired to eat properly. And I’m not even talking about the quality and how tasty it is, so to speak.Technology develops very fast and contributes to safe and challenging rehabilitation. Currently, eHealth is not often used in the GR, but as one nurse practitioner summarized:Well, it has a lot of potential, but the tricky thing is, there are so many applications. Remember you are dealing with elderly people who have difficulty with technology and you have to organize your whole care process in such a way that the technology takes this into account. So, to implement it properly, there are quite a few conditions to meet.Four main themes belong to this category: (1) environmental aspects; (2) staff aspects; (3) organizational aspects; and (4) factors outside the ward.The environment on a rehabilitation ward must be safe and must invite rehabilitants to practice as much as possible. As one physical therapist said about the building aspects of a rehabilitation ward:It is an interaction of a warm environment that is very stimulating and invites to start doing the things required to be able to go home.It is important that the environment resembles the domestic situation as much as possible, and everyday equipment is used. The environment should stimulate rehabilitants to practice as much as possible, and rehabilitants must have access to exercise materials all day. This can be achieved by providing exercise opportunities in the corridors and possibilities to go outside. As one manager said:When you get to the point in the rehabilitation process that you are able to practice independently on the parallel bars, then you want to do that as often as possible, I’d think. I would like to have that nearby or be allowed to go there on my own to practice. Then I can imagine it being on the ward is convenient.A rehabilitation team must work in an interdisciplinary way, and the rehabilitant and their informal caregiver are seen as part of the team as well. As an elderly care physician explained:If you are referring to interdisciplinary working. That’s a core concept in rehabilitation. You have the specialist expertise in all fields, but you also have to know and be able to borrow from each other’s expertise a little bit.All employees must have an emphatic, motivating attitude and stimulate rehabilitants to practice throughout the day. As a rehabilitation physician stated:I think, particularly nursing staff having a rehabilitation focus, and so, encouraging for the patients to do everything possible they can, from the start. So, that may make a significant difference.As rehabilitants in the GR do not always fit in medical guidelines, staff must be able to work based on the ideas of evidence-based practice. As one physical therapist said:That is the problem with the application of such a guideline. For example, the guideline says it’s for stroke, but if someone also has Parkinson’s, or broke his hip last year, you cannot do certain tests. Because it’s obviously impossible.Even though internationally organizational aspects differ and can therefore influence the rehabilitation process, the concept of CRE is suitable to get the most out of rehabilitation. Implementing a CRE requires a shared vision on rehabilitation and a balanced interdisciplinary team with sufficient time for the implementation. As a nurse practitioner said:I do think when you have that kind of project group, it does involve regular evaluation. Like, guys, how are the things we started going now? And do we need to adjust, fine-tune anything.CRE does not depend on the rehabilitation setting, as long as the name of the ward does not generate false expectations. It is also important that rehabilitants are not addressed as patients. As a nurse lecturer said:Calling someone patient or client, you emphasize what a person can’t do. If you say person, you avoid this label. It is still someone who tries to live his life in the best way possible.The discharge process must be well prepared and supervised. Home visits allow rehabilitants to practice meaningful tasks in their own environment in preparation for their discharge. One manager with a background as physical therapist mentioned:It also helps to have people actually go home during rehabilitation. This provides so much information about how they actually function at home. A situation is always different at home.Although participants think it is a good idea to organize rehabilitation in the home situation as soon as possible, they also doubt whether it is better to keep rehabilitants on the rehabilitation ward for longer. As an elderly care physician said:The question is, if you have a ward with a very good rehabilitation climate, would you not want to admit patients there who, in terms of their care needs, could go home, but for whom the added value of the rehabilitation climate for the rehabilitation is such, that patients choose to be admitted to the department for rehabilitation.This article is the first to describe the perspectives of healthcare professionals in rehabilitation, concerning CRE. A set of seven factors concerning rehabilitation processes and four factors concerning organizational aspects emerged from the qualitative data. The results of this study are  in line with our review on CRE and confirm the importance of increasing therapeutic intensity, the importance of patient-regulated exercise, group training and task-oriented training in a CRE. Involving informal caregivers, providing a challenging environment for rehabilitation, and a cooperating, motivating team are also aspects of a CRE. These factors, therefore, constitute challenges for a rehabilitation team to work on .Participants in the current study believe a CRE is suitable for all types of rehabilitants, but it has to be tailored to the resilience, goals, and cognition of the rehabilitant. This is in line with recent literature, which states that rehabilitation is suitable for persons with all kinds of diagnoses when it is tailored to the needs, goals, and wishes of the individual rehabilitant ,20. ThisThe results of this study indicate that it is important in a CRE to work on a rehabilitants’ own goals and to measure them with appropriate measurement instruments. Although a recent meta-analysis could not substantiate its added value, they do see goal setting as a part of shared decision-making and as a way to respect the preferences, values, and autonomy of rehabilitants . A recenParticipants in this study feel that attention to the nutritional status of a rehabilitant is relevant and an optimal “food as usual” but protein-rich diet should be the goal. This is endorsed by recent literature that indicates that the nutritional status is significantly related to successful rehabilitation in older adults ,24. The Although eHealth is currently not often used in GR, participants do see a lot of potential in eHealth for exercising, monitoring and safety during practice. Applications must be suitable for the target group. Systematic reviews show the benefits of eHealth for older persons in terms of increasing their physical activity, walking ability, and balance ,26,27. AA CRE can be negatively affected by organizational aspects such as funding, administrative tasks, and legal regulations, which can differ internationally. Participants think it is important that an organization has a shared vision on rehabilitation and there is sufficient time for implementing a CRE. Implementing a complex concept such as the CRE should be based on an understanding of the behaviors that need to change, the relevant decision-making processes, and the barriers and facilitators of change. Monitoring during and after the implementation is crucial . The litParticipants stressed the importance of practicing meaningful tasks in a rehabilitant’s own environment and thus of rehabilitation in the home situation as quickly as possible. However, some are in doubt as to whether a longer stay on the rehabilitation ward is better if there is a good CRE. As the effectiveness and efficiency of CRE have not yet been studied, no statement can be made about the benefits of inpatient rehabilitation in a good CRE versus outpatient rehabilitation at one’s own home. This needs to be the subject of further research.The 11 themes that were identified form a rather complex concept. In general, the rehabilitation process should be individually tailored and optimized to achieve all the goals of the rehabilitant. Currently, all principles of CRE are used internationally in GR. However, the rehabilitation ward may not work according to all of the themes that are important for a CRE. Therefore, new interventions should be implemented and adapted.The strength of this study is the number of participants. We interviewed more than 200 individuals, and data saturation was reached. Secondly, all professionals participating in this study had experience in the field of rehabilitation. The occupation of the participants was taken into account in the composition of the focus groups. Therefore, hierarchical differences did not prevent participants from discussing their ideas, although it also limited the exchange of ideas between groups. In the workshops, participants were mixed in smaller groups regardless of occupation. The results of these workshops were in line with the results of the focus groups, meaning that occupation did not influence the results. The use of focus groups and workshops stimulated the exchange of ideas, which also resulted in new ideas. Participants were asked for subjects they thought were important for a CRE, even when not asked for by the researchers. In this way, it was ensured that all relevant topics were discussed and the internal validity of the study was increased.A limitation of our study is that most participants are from the Netherlands and were somehow familiar with CRE ideas. This may limit the generalizability of the results to GR in other countries in which the concept of CRE is in its infancy. However, the topics discussed in the non-Dutch focus group at the 2019 EuGMS congress were in line with the results of the other focus groups. We, therefore, think that the identified themes are important for all rehabilitants in GR, regardless of the country in which they are rehabilitating. Based on this study, 11 themes were identified for modeling a CRE. Overall, it is important to tailor the rehabilitation process to the rehabilitant and to stimulate rehabilitants to optimize their rehabilitation. Since tailoring the rehabilitation process in a CRE to rehabilitants and their informal caregivers seems important, it is interesting to investigate whether these eleven themes are supported by the rehabilitants themselves and to find out if they consider other factors important for a CRE. According to the respondents, to offer effective rehabilitation, all elements of CRE should be applied, and specific interventions need to be developed and implemented. Consequently, the effectiveness and efficiency of CRE need to be studied with validated tools that are yet to be developed. In our ongoing research, we aim to develop those tools.


To assess the efficacy of home-based cardiac rehabilitation and traditional outpatient rehabilitation in stage II after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).  From September 2019 to March 2020, 80 AMI patients in Cangzhou Central Hospital were randomly assigned to one of the two groups: the control group or the observation group, 40 cases in each group. The control group received old-fashioned outpatient rehabilitation treatment, and the study group received long-distance family rehabilitation nursing intervention. The blood pressure, examination results, compliance, satisfaction evaluation, incidence of cardiac events, heart rate, quality of life score, and 6-minute walking test were compared between the two groups. P < 0.05). There were substantial variances in left ventricular discharge portion, low-density lipoprotein, medication compliance, satisfaction, and quality of life (P < 0.05); there was substantial inconsistency in the 6-minute walking test concerning the two groups afterwards discharge for 3 months (P < 0.05).  There were no deaths in both groups. There were significant differences in heart failure, unstable angina pectoris, unplanned readmission rate, walking compliance, and 6-minute walking test at 6 months after discharge ( Home rehabilitation is a new home cardiac rehabilitation model with high efficiency, convenience, and whole process monitoring and barrier-free follow-up management. It can effectively improve the cardiac function, workout patience and worth of life expectancy of victims with AMI, improve their self-management awareness and rehabilitation compliance, reduce the risk of cardiac events, and have a positive impact on the prognosis and rehabilitation of patients with AMI. Acute myocardial infarction (AMI) is caused as a result of severe and lasting ischemia or necrosis of the corresponding myocardium because of the sharp drooping or interruption of blood supply on the basis of coronary artery dysfunction . AMI is Cardiac rehabilitation and prevention can fundamentally reverse the simple biomedical model. Cardiac rehabilitation reduces the sudden death rate, recurrence rate, and readmission rate of cardiovascular disease through the combination of five core prescriptions . Cardiac rehabilitation can be divided into three stages: stage I, hospitalization rehabilitation, 4–7 days after onset; II stage, outpatient rehabilitation, 7 days to 3–6 months after onset; and the third stage, family rehabilitation, from 6 months after onset to the whole life process . The traTherefore, the proposed study on victims with acute myocardial infarction PCI postoperative stage II remote home rehabilitation, compared with old style casualty rehabilitation efficacy , hope byP > 0.05). Participants in randomized controlled trials are randomly allocated to either the treatment or control arms. The practice of arbitrarily allocating sample members to treatment or control arms is referred to as randomization. To randomly select, a variety of tools can be utilized . The two factors of randomization are the creation of a random pattern and the implementation of such a random pattern, ideally in a way that leaves participants unaware of the sequence . The danger of systematic error or prejudice is eliminated by randomization. The most important benefit of an RCT is that it accounts for both predictable and unpredictable confounding variables, which can result in errors.Eighty patients having acute myocardial infarction who received emergency PCI in Cangzhou Central Hospital in the period of September 2019 to March 2020 were nominated for the examination as objects. The parallel randomized control method was used in the proposed study, and selected patients were arbitrarily allotted to one of two groups: observation or control, considering 40 cases for each group. In the observation group, there were 27 males and 13 females, (55.4 ± 8.9) years old, while in the control group, 25 males and 15 females, (55.6 ± 8.3) years old. There was no significant difference in general data between the two groups  ; emergenExclusion criteria were as follows: the history of myocardial infarction; there are serious complications, such as cardiogenic shock, severe arrhythmia, severe congestive heart failure, hypotension, obvious persistent or episodic chest pain, and mechanical complications; a history of mental disorders; serious other diseases, such as serious cerebrovascular disease sequelae, mobility inconvenience and physical disability and other factors affecting sports, severe anemia, and serious chronic lung diseases.Exercise prescriptions were formulated as stated by the strategies of the American College of Sports Medicine , and theChest tightness, chest pain, and shortness of breath appear after exercise. The heart rate after activity was lower than 50 beats/min or more than 130 beats/min. Postactivity Brog rating was >15.Walking frequency ≥50 times is considered as compliance standard . Those wThe nurses collected and sorted out the patients' heart rate, blood pressure, laboratory results, compliance, satisfaction assessment, incidence of cardiac events, quality of life score, and 6-minute walking test.χ2 test was used. P < 0.05 was considered as statistically major difference.The statistical software SPSS 17.0 was used to analyze the data. The statistical data were expressed as percentage (%), and the χ2. The χ2 test could be used to evaluate if two variables are highly correlated or not.The chi-square 2 statistic measures the difference between the observed and predicted probabilities of the consequences of a series of actions or variables. The chi-square test is a useful tool for determining category differences, especially those that are only nominal. The sample size, the degree of freedom, and the amount of the disparity in actual and recorded values all have an impact on the value of P < 0.05) ; there were significant differences in LDL, satisfaction, and left ventricular ejection fraction (P < 0.05).The difference of unplanned readmission rate was statistically significant (Most of your body's cholesterol is made up of LDL (low-density lipoprotein), also known as “bad” cholesterol. LDL cholesterol levels that are too high put you at risk of heart disease and stroke.To compute LDL, the following given formulation is used:P < 0.01). There was no substantial change in the occurrence and mortality of reinfection (P > 0.05).There was major change in the occurrence of unstable angina pectoris and congestive heart failure (P > 0.05). 3 months after discharge, the difference was statistically significant (P 0.05). The variance was statistically substantial 6 months after discharge (P < 0.01).There was no statistically substantial transformation between the 6-minute walking test at releasing and one month later (P < 0.05).There was significant difference in the scores of life quality between the two groups at 6 months after discharge (P 0.05) than the control groups, whereas the 6-minute walking test and quality of life were significantly greater (P 0.05). The rates of reinfection and mortality in the two groups were not significantly different. Home rehabilitation may help AMI patients improve their heart function, activity tolerance, and quality of life, but not increase the incidence of cardiac events and mortality, so it is safe and feasible for patients.The remote home rehabilitation mode of “Internet+ integrated medical care rehabilitation team” was applied to form a comprehensive, quantitative, individual, and sustainable new mode of home exercise rehabilitation, which improved the participation and safety of cardiac rehabilitation for AMI patients . The proAMI guidelines of the European Cardiology Society in 2012 pointed out that walking is the best way for stage II rehabilitation of AMI patients . Since eAccording to some researchers, cardiac rehabilitation must be done through exercise under medical observation . In the Six months after discharge, the walking compliance of patients in the control group was only 50% (20/40) and that of patients in the study group was about 95% (38/40), which was similar to foreign studies . Two groIn this respect, we suggest a procedure for implementing a statistical approach to questionnaire validation that incorporates exploratory factor analysis and reliability analysis. The research focuses on the psychometric examination of data from a survey.The home cardiac rehabilitation mode effectively ensures the safety and scientific nature of stage II home rehabilitation for AMI patients, improves patient compliance and quality of life, and is worthy of promotion through the standardized walking program, real-time monitoring of heart rate by APP or exercise bracelet, and barrier-free follow-up management on WeChat platform of medical rehabilitation team. The limitation of the projected study is that only exercise and medication intervention were carried out. With the development of information technology and cloud technology, more rehabilitation procedures and simple and effective monitoring equipment should be developed in the future, and behavioral intervention should be included in the stage II cardiac rehabilitation of AMI patients, so as to make cardiac rehabilitation more humanized, individual, convenient, and systematic.


Compared to seed propagation, clonal propagation is a simpler, faster, and more efficient method to rapidly expand millions of cuttings from elite germplasms . AdventiDue to the recalcitrance of AR formation in many tree species, the application of exogenous hormones becomes a major approach for optimizing clonal propagation . Here, wFour stages are included in the AR formation process : activatJuglans nigra L.) (Robinia pseudoacacia L.) (Populus tremula (Betula pendula) B1 genotype 6-fold higher than in non-rooting birch B2 genotype  , black lacia L.) , and Pop tremula , which m tremula . Further tremula . Moreove tremula . For exa tremula , and cyt tremula . Besidesgenotype ; jasmoniem cells . Therefoin vitro in the presence of exogenous hormones supplementation and was also successfully grown in a rooting mixture of peat and perlite   (Tectona grandis)  stock resulted in the AR formation of cuttings increased  , eucalyplobulus) , and teagrandis)  Table 1Castanea reatment , suggestncreased . TherefoAnacardium occidentale L.) and chestnut, are highly recalcitrant to in vitro culture and clonal propagation as the astrict to form AR (Camellia sinensis L.) (Cutting and tissue culture offer prospects for faster multiplication of elite trees . Unfortu form AR . In orde form AR . Transcr form AR  and nodansis L.) , respectin vitro in the presence of IAA inhibitors caused complete inhibition of rooting  cuttings and increased the number of AR per cutting (Pinus banksiana) cuttings of different tree ages  and found that NAA treatment generally increased rooting by 2-3 fold compared to controls. In apple  propagation, the rooting rate in cutting is significantly higher after treatment under 3 g/L IBA with 50 mM H2O2 since H2O2 significantly enhances the effect of IBA on rooting (Olea europaea ‘Manzanilla') treated under 3 g/L IBA showed a 1.8-fold increase in rooting rate  (Azadirachta indica) formed AR under MS medium with 1 mg/L IBA supplementation  . Cuttingm album) . The prem album) . Therefoentation , and theentation . Exogenoentation . Based oP. alba × P. glandulosa) (Populus × euramericana ‘Neva') rooting induction medium  , while 0n medium . In addiglobulus . TogetheVitis sp.) cuttings  cuttings formed significantly more adventitious roots when the cuttings dipped with 8 g/L IBA than that formed in 3 g/L IBA (in vitro multiplication.The proper concentrations of plant growth regulators are important because excessive auxin concentrations may inhibit AR initiation , suggestcuttings . In addicuttings . Converscuttings , and Euc g/L IBA . TherefoAdventitious rooting is indispensable for the vegetative propagation of forestry and horticultural plants. A good rooting system is necessary for plants to adapt to various environments and increase yields, as it can absorb more nutrients for the growth of the above-ground parts. Therefore, advances in the knowledge of AR formation will pave the way for optimizing clonal propagation in woody species. Internal and external factors impact AR formation, of which, auxin as the master hormone regulator seems to be the most important and central one. Despite advances in exogenous hormone selection and concentration over the past few decades, the response of inter-species variation in woody plants to different hormones and their impact on AR formation remain unclear. Therefore, the mechanism of auxin and other hormones in AR formation in diverse woody plants still needs to be analyzed, in order to improve the efficiency of clonal propagation by applying exogenous hormones.


Calculations suggest this results from the absence of a second ortho-substituent on the boron-bound aryl rings, which enables their free rotation and exposes the B–B bond to nucleophilic attack. 7-Phen and 7-Pyr are obtained by the reduction of the corresponding 1,2-diaryl-1,2-dichlorodiborane precursors, B2Ar2Cl2(PMe3)2, obtained from the SMe2 adducts, which are synthesised by direct NMe2–Cl exchange at B2Ar2(NMe2)2 with (Me2S)BCl3. The low-lying π* molecular orbitals (MOs) located on the PAH substituents of 7-Phen and 7-Pyr intercalate between the B–B-based π and π* MOs, leading to a relatively small HOMO–LUMO gap of 3.20 and 2.72 eV, respectively. Under vacuum or at high temperature 7-Phen and 7-Pyr undergo intramolecular hydroarylation of the B PBM data was replaced with SVG by xgml2pxml:<glyph-data id="z.dbd" format="PBM" resolution="300" x-size="8" y-size="10" xml:space="preserve">00000000000000000000000000000000111111110000000011111111000000000000000000000000</glyph-data><svg xmlns="http://www.w3.org/2000/svg" version="1.0" width="13.200000pt" height="16.000000pt" viewBox="0 0 13.200000 16.000000" preserveAspectRatio="xMidYMid meet"><metadata>Created by potrace 1.16, written by Peter Selinger 2001-2019</metadata><g transform="translate scale" fill="currentColor" stroke="none"><path d="M0 440 l0 -40 320 0 320 0 0 40 0 40 -320 0 -320 0 0 -40z M0 280 l0 -40 320 0 320 0 0 40 0 40 -320 0 -320 0 0 -40z"/></g></svg>B bond to yield 1,2-dihydronaphthodiborole derivatives. Hydrogenation of 7-Phen, 7-Pyr and their 9-anthryl and mesityl analogues III and II, respectively, results in all cases in splitting of the B–B bond and isolation of the monoboranes (Me3P)BArH2. NMR-spectroscopic monitoring of the reactions, solid-state structures of isolated reaction intermediates and computational mechanistic analyses show that the hydrogenation of the three PAH-substituted diborenes proceeds via a different pathway to that of the dimesityldiborene. Rather than occurring exclusively at the B–B bond, hydrogenation of 7-Ar and III proceeds via a hydroarylated intermediate, which undergoes one B–B bond-centered H2 addition, followed by hydrogenation of the endocyclic B–C bond resulting from hydroarylation, making the latter effectively reversible.The classical route to the PMe In contrast to classical B–B bond-centred diborene hydrogenation, polycyclic aromatic hydrocarbon-substituted diborenes first undergo thermal intramolecular hydroarylation, followed by hydrogenation of the remaining B–B and endocyclic B–C bonds. For example, changing the NHC and duryl ligands in diborene I  substituents of III,12 the energy of the HOMO is slightly lowered but, most importantly, two of the π* orbitals of the anthryl fragments (in-phase and anti-phase) intercalate between the B–B π and π* orbitals , thereby lowering the HOMO–LUMO gap to only 1.07 eV. This orbital intercalation adds to the usual B–B bond-centred reactivity of diborenes the possibility of aryl-centred reactivity, as borne out by the intramolecular C–H borylation of the anthryl moiety in reactions with selenium and copper triflate.12,24The stereoelectronic nature of the substituents of the Bborene I 21 to PMeortho positions, which locks these substituents in a position orthogonal to the plane of the diborene core. In order to increase the reactivity of diaryldiborenes even further we aimed to synthesise new polycyclic aromatic hydrocarbon (PAH)-substituted diborenes with a similar frontier orbital arrangement as III, but in which the boron-bound aryl ring bears only one ortho substituent, such as the 9-phenanthryl and 1-pyrenyl groups displayed in 3-stabilised diphenanthryl- and dipyrenyldiborenes, and secondly make the latter thermally unstable towards intramolecular C–H borylation. Furthermore, we examine the hydrogenation mechanism of PAH-substituted diborenes relative to that of the dimesityldiborene III, both experimentally and computationally.Thus far, all known diaryldiborenes bear very sterically demanding aryl substituents, substituted in both 2Ar2Br2 (3-Ar), in the presence of PMe3.12,22 The precursors 3-Ar are obtained via a three-step procedure by (a) arylation of B2X2(NMe2)2  with LiAr to yield 1-Ar, followed by (b) acidic methanol quenching to yield 2-Ar, and finally (c) bromination to yield 3-Ar (25–27 Attempts to synthesise the corresponding diphenanthryl- and dipyrenyldiboranes(4) following the same procedure failed as step (b) was systematically followed by B–B bond cleavage of 2-Ar during workup. Although 2-Ar was detected in the 11B NMR spectrum of the reaction mixture at ca. 59 ppm (2-Mes: δ11B = 61 ppm),26 workup systematically led to the isolation of the dimethoxyboranes 4-Ar 28 as the sole isolable products (2O or toluene), solvents , workup temperatures  and procedures  all led to the isolation of the monoboranes 4-Ar as the major product in up to 77% yield  level of theory show that 2-Phen and 2-Pyr each have three stable rotational isomers, depending on the relative orientation of the two unsymmetrical aryl substituents  torsion angle (2a-Pyr 22.2°). For comparison, the (C–B–B–C) torsion angles in the solid-state structures of 2-Mes and 2-Anth are ca. 104° and 125°, respectively.12,26 The isomer in which both ortho protons point towards each other, 2b-Pyr, is of similar energy to 2a-Pyr. The third isomer, in which both ortho protons point in the same direction, 2c-Pyr, lies only 2.0 kcal mol−1 higher in energy than 2a-Pyr. For the phenanthryl derivative the trend is reversed, 2c-Phen being 2.9 kcal mol−1 more stable than 2a-Phen, in which the π overlap is far less pronounced than in 2a-Pyr, due to a much larger (C–B–B–C) torsion angle of 65°. In both cases, however, the asymmetry of the energetically accessible 2c-Ar conformation, combined with the much lower steric protection afforded by the 9-phenanthryl and 1-pyrenyl ligands when compared to the mesityl and 9-anthryl ligands, may be the cause of the increased instability of 2-Phen and 2-Pyr, presumably promoting nucleophilic attack of unreacted MeOH at the B–B bond. The exact mechanism of the conversion from the diboranes 2-Ar to the monoboranes 4-Ar, however, remains unclear.Since tituents . For the2–Br exchange using (Me2S)BBr3 as the bromide source.29 While 1-Ar  underwent NMe2–Br exchange with (Me2S)BBr3 as shown by the formation of BBr2(NMe2) (δ11B = 26 ppm),30 the reaction did not yield the desired 1,2-diaryl-1,2-dibromodiborane, but instead a complex mixture of products, including some resulting from B–B bond splitting. In contrast, the reaction of 1-Ar  with 2.1 equiv. (Me2S)BCl3 in benzene proceeded cleanly over a period of 5 days at room temperature to afford the SMe2-stabilised precursors 5-Ar in 90% (Ar = Phen) and 84% (Ar = Pyr) isolated yields , isolated in 83% (Ar = Phen) and 86% (Ar = Pyr) yields  yields .31–34 The eclipsed conformation might be favoured in this case by attractive interactions between the two PAH groups. The B–B bond lengths of 1.776(4) and 1.779(7) Å for 6-Phen and 6-Pyr, respectively, are within the range typical for acyclic doubly base-stabilised diboranes.31–34The solid-state structures of 6-Phen and 6-Pyr show an unexpected eclipsed conformation of the substituents at the two boron atoms .12 Interestingly, the 1H NMR spectrum of 7-Phen showed the presence of two isomers, which were identified as two rotamers of 7-Phen, the centrosymmetric species 7a-Phen and its isomer 7b-Phen, in which one of the phenanthryl substituents is rotated by 180° compared to 7a-Phen  is within the range usually observed in diborenes (1.52–1.62 Å).1,12,21,35A single-crystal X-ray diffraction analysis of 7a-Phen confirmed the formation of the diborene . The strB double bond and that of the phenanthryl units are likely unconjugated, as the C2–C1–B1–B1′ torsion angle is ca. 78.7°. The computed structure of 7-Pyr also shows a very similar B–B bond length (1.575 Å) and a larger C2–C1–B1–B1′ twist of 105.4°.The computed structure of 7a-Phen also displays a very similar B–B bond length . In terms of engineering a small HLG in diborenes by incorporating PAH substituents, phenanthryl and pyrenyl groups show no advantage over anthryl groups, even if the HLG of 7-Pyr is close to that of III .1211B NMR resonances at −13 and −22 ppm, and two broad 31P NMR doublets at −5 and −9 ppm (3JPP = 84 Hz), indicative of an unsymmetrical doubly PMe3-stabilised diborane. Upon removing all volatiles in vacuo, the diborene 7-Ar converted entirely to 8-Ar, isolated as a colourless solid in 50% yield for Ar = Phen and as a yellow solid in 55% yield for Ar = Pyr .During the reduction of 6-Ar to 7-Ar, a small amount of by-product 8-Ar was formed, which displays two broad Ar = Pyr . The 1H 3-stabilised 4-(9-phenanthryl)-5-hydro-phenanthrodiborole  or by heating the reaction mixture for 2 days at 120 °C for complete conversion. The anthryl derivative III could also be partially converted to 8-Anth over a period of several days in refluxing toluene but was stable under vacuum. This increased reactivity of 7-Phen and 7-Pyr compared to III is likely due to the lower steric shielding of the boron centres provided by the unsubstituted ortho position of the 9-phenanthryl and 1-pyrenyl ligands. The B–B bond in 8-Phen (1.795(2) Å) is slightly longer than in the hydroarylated anthryl derivative (1.782(2) Å)36 due to the additional presence of the hydride ligand at B1. The phenanthrodiborole ring is not fully planar and shows a slight curvature of the PAH backbone (the mean planes of the three C6 rings form angles of 1.9 and 4.1° between each other) and a slight twist in the 1,2-diborole ring (torsion angles C1–B1–B2–C3 11.35(11), C2–C3–B2–B1 −9.43(12), C2–C1–B1–B2 −10.70(12)°) caused by the ring strain of the C3B2 ring.‡The boron-bound hydrides were detected in the inverse Fourier map and freely refined.A single-crystal X-ray analysis showed that 8-Phen is the product of the intramolecular hydroarylation of diborene 7-Phen, which generates a doubly PMediborole . A simil2 resulted in twofold hydrogenation and splitting of the B–B bond to yield the phosphine-stabilised arylboranes 10-Ar, characterised by an 11B{1H} NMR doublet at ca. −25 ppm (2JBP ≈ 50 Hz) and a broad 31P{1H} NMR multiplet around −8 ppm , stabilised by a single PMe3 ligand, which results from the single hydrogenation of the B–B bond of 8-Anth with loss of one PMe3 ligand 2 proceeded stepwise, enabling the isolation of the single hydrogenation intermediate B2I2H2(PMe3)2.40In comparison, the hydrogenation of the related dimesityldiborene II required heating in benzene for 9 days at 80 °C under 5 bar of H2 . Althougortho-methyl group to form a 2-benzyl unit bridging two boron centres,41,42 the known hydrogenation mechanism for B2I2(PMe3)2via B2I2H2(PMe3)240  makes a similar stepwise hydrogenation of IIvia B2Mes2H2(PMe3)2 more likely. We envisage that the initial competition for activating the intramolecular aryl C–H bond of fused arenes or the H–H bond of H2 by the diborenes, after PMe3 dissociation, decides the fate of the mechanism. This view puts forward that diborenes 7-Phen, 7-Pyr and III perhaps follow the C–H activation route, while diborene II, lacking a nearby aryl C–H bond, may follow the H–H activation route. To ascertain this, computations were performed on both pathways for all diborenes. The pathways computed for 7a-Phen and II are shown in Although a similar hydrogenation mechanism to that of III, 7-Phen and 7-Pyr may be envisaged for diborene II, since mesityl-substituted diboron compounds are known to undergo intramolecular C–H activation at one 10-Ar is substantially exergonic, with ΔG ranging from −47.6 to −51.1 kcal mol−1. Although the initial step of PMe3 dissociation from all diborenes, leading to intermediate 12-Ar, is significantly endergonic, it has a relatively low energy barrier of 22.7 to 24.4 kcal mol−1. In the next step, intermediates 12-Phen, 12-Pyr and 12-Anth all show almost an equal propensity towards C–H (black profile) and H–H activation (blue profile), with the overall energy barriers for these two processes from 7-Ar and III separated by only 0.4 to 2.1 kcal mol−1 ) and explains the high reaction temperature required for full conversion. The alternative pathway, via loss of PMe3 to generate 15-Ar, followed by H2 activation (red profile), is energetically less favourable by 3 to 5 kcal mol−1.The twofold hydrogenation of all diborenes to the boranes al mol−1 . For theII, as activating the ortho-methyl C–H bond of the mesityl substituent is energetically less favoured ) than the activation of H2 , 2 activation across the BB bond, leading to the resting species, the doubly PMe3-stabilised 1,2-dihydro-1,2-dimesityldiborane 11-Mes. This species loses one PMe3, leading to the hydride-bridged diborane 17-Mes, which activates the second equivalent of H2 across the B–B single bond, ultimately forming the product 10-Mes. Following previous reports of symmetrical di- and tetraaryldiboranes(4) spontaneously activating dihydrogen across their B–B bond,43,44 this pathway was also computed using the diborane(4) intermediate 19-Mes, generated from 17-Mes through PMe3 dissociation, but proved less competitive for the formation of 10-Mes (red profile). For the whole hydrogenation reaction of diborene II, the first H2 activation step (II-to-17-Mes) is rate-limiting .Competition for the initial C–H or H–H activation is not seen with diborene 2 addition proceeds directly across the B–C bond of 9-Ar. In contrast, for diborene II, it is clear-cut that both the first and second hydrogenation occur essentially across the B–B core.Overall, computations reveal that for diborenes 7-Phen, 7-Pyr and III, both C–H and H–H activation pathways initially compete almost equally to establish the observed resting species 9-Ar, while the second H3-stabilised dimesityl- and dianthryldiborenes II and III, the synthesis of the analogous 9-phenanthryl and 1-pyrenyl-substituted diborenes 7-Phen and 7-Pyr is fraught with complications owed to the absence of a second ortho substituent at the boron-bound aryl rings. The reduced steric bulk of these PAH substituents enables their free rotation, thus exposing the B–B bond of both diborane precursors and diborenes to decomposition. Systematic B–B bond cleavage during the usual synthetic route via B2Ar2(OMe)2 precursors can be circumvented by direct NMe2–Cl exchange at B2Ar2(NMe2)2 precursors with (Me2S)BCl3. The resulting isolable SMe2 adducts of B2Ar2Cl2 can be converted to the PMe3 adducts, which can in turn be reduced to the desired diborenes 7-Phen and 7-Pyr. The facile rotation of the 9-phenanthryl substituent is evidenced by the existence of two energetically equivalent rotational isomers of 7-Phen in solution. DFT calculations show that, as in III, the low-lying unoccupied π* orbitals of the PAH residues of 7-Phen and 7-Pyr are intercalated between the π and π* orbitals of the B–B bond to furnish a small HOMO–LUMO gap, albeit a slightly larger one than in III. Both 7-Phen and 7-Pyr were only stable in solution at rt in the presence of PMe3, thus marring their clean isolation in the solid state. At high temperature in solution or under vacuum 7-Phen and 7-Pyr underwent intramolecular hydroarylation of the BB bond to yield the 1,2-dihydronaphthodiborole derivatives 8-Ar. The analogous 8-Anth could also be obtained, albeit in much lower yield, by refluxing III in toluene for several days.Unlike the straightforward syntheses of the PMe2 required prolonged reaction times and high temperatures. NMR-spectroscopic monitoring of the reactions showed that they proceeded through the formation of the hydroarylation intermediates 8-Ar, followed by hydrogenation of one boron moiety of 8-Ar to yield the intermediates 9-Ar, of which the anthryl derivative was structurally characterised, and finally a second hydrogenation of the B–C bond resulting from hydroarylation to yield the monoboranes (Me3P)BArH2 (10-Ar). The hydrogenation of the mesityl derivative II, which required 5 bar H2, longer reactions times and yielded the analogous monoborane 10-Mes, did not show any stable reaction intermediates. Computational mechanistic analyses using DFT showed that the hydrogenation of II proceeds by two successive H2 additions to the B–B bond. In contrast, hydrogenation of the PAH derivatives can proceed either via H2 addition at the B–B bond first and intramolecular hydroarylation second, or vice versa, both pathways converging in the second H2 addition, which splits the B–C bond formed in the hydroarylation step. This unprecedented, uncatalysed hydrogenative B–C bond cleavage constitutes the rate-limiting step and effectively reverses the intramolecular hydroarylation process.The twofold hydrogenation of the PAH-substituted diborenes with 1 bar HFinally, it must be noted that the use of phenanthryl and pyrenyl substituents in both diborane and diborene chemistry affords clear disadvantages over hitherto employed aryl substituents. This is due on the one hand to the lack of steric protection of the B–B bond, which often leads to decomposition, on the other hand to the insoluble nature of both the desired products and side products, which frustrates efforts to purify the compounds.The datasets supporting this article have been uploaded as part of the ESI.†A. O. designed and carried out 90% of the experimental work. L. E., T. S. and J. W. carried out the remaining 10% of the experimental work. A. J. carried out the majority of theoretical calculations. M. A. wrote the manuscript, refined X-ray structures and carried out preliminary computations. A. O., A. J., L. E. and M. A. co-wrote the ESI. C. B., M. H., A. L., C. L. and M. R. carried out X-ray crystallographic experiments. H. B. designed the original project and provided the funding.There are no conflicts to declare.SC-013-D2SC02515A-s001SC-013-D2SC02515A-s002


Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) during androgen deprivation therapy (ADR) in early stages of prostate cancer. Thus, rather than blocking the androgen-related pathway further, docetaxel (DTX)-based therapy has become the most effective and standard first-line chemotherapy for CRPC. Although the therapy is successful in prolonging the survival of patients with CRPC, chemotherapy resistance develops due to the abnormal activation of the androgen receptor (AR) signaling pathway. Thus, to optimize DTX efficacy, continued maximum suppression of androgen levels and AR signaling is required. Here, we designed a prostate-specific membrane antigen (PSMA)-targeted nanosystem to carry both DTX and AR siRNA (Di-PP/AR-siRNA/DTX) for CRPC treatment. Specifically, DTX was encapsulated into the hydrophobic inner layer, and the AR siRNA was then condensed with the cationic PEI block in the hydrophilic outer layer of the PEI-PLGA polymeric micelles. The micelles were further coated with PSMA-targeted anionic polyethylene glycol-polyaspartic acid (Di-PEG-PLD). In vitro and in vivo results demonstrated that the resulting Di-PP/AR-siRNA/DTX exhibited prolonged blood circulation, selective targeting, and enhanced antitumor effects. Consequently, Di-PP/AR-siRNA/DTX holds great potential for efficient CRPC treatment by combining chemotherapy and siRNA silencing of androgen-related signaling pathways. Prostate cancer (PC) was the most common cancer diagnosed in men in the United States in 2021, accounting for 26% of the diagnoses and causing the second highest number of deaths in men ,4. WorseThe FDA has approved mitoxantrone, DTX, and cabazitaxel as treatment drugs for CRPC. Mitoxantrone was approved for CPRC in 1996; however, it has been clinically proven that the drug only relieves the pain of bone metastasis and cannot prolong the overall survival of patients . In 2004The human AR gene is located at q11–12 of the X chromosome and contains eight exons and seven introns. The full length of the gene is approximately 90 kb, the molecular weight is approximately 110 kD, and it encodes 918 amino acids . Under nLuckily, the availability of successful drug delivery carriers has opened up bright prospects for tackling the aforementioned issues. Recently, amphiphilic copolymers, especially those with hydrophobic segments to encapsulate hydrophobic compounds and hydrophilic positively charged shells to condense nucleic acids, have received great attention. Polyethylenemine (PEI), poly(dimethylaminoethyl methacrylate) (PDMAEMA), and poly(2-aminoethyl ethylene phosphate) (PPEEA) are the most frequently used cationic segments, and the most popular hydrophobic polymers are polylactide(PLA), poly(ε-caprolactone) (PCL), and poly(lactic-co-glycolic acid) (PLGA) . HoweverCombining these ideas, we first designed a PSMA-targeted nanosystem to carry both DTX and AR siRNA (Di-PP/AR-siRNA/DTX) for CRPC treatment . In deta2000-COOH) was purchased from Jinan Daigang Technology Co . Branched polyethyleneimine  was obtained from J&K Chemical Ltd. N-maleimide-PEG5k-PLD10 and Dipeptide (WQPDTAHHWATL) were commercially obtained from Tanshu-Tech . Docetaxel was provided by Aladdin Reagent Database Inc. . Anti-androgen receptor siRNA (siRNA: 5′-AAGAAGGCCAGUUGUAUGG AC-3′) and Cy5-siRNA were synthesized by GenePharma Co., Ltd. . Ethidium bromide (EtBr) and 6-coumarin  were obtained from Sigma-Aldrich Inc. . Fetal bovine serum (FBS) and RPMI-1640 media were purchased from GIBCO, Invitrogen Corp. . A cell counting kit-8 (CCK-8) was obtained from Dojindo Laboratories . The primary antibody against androgen receptor used for WB and IHC was purchased from Abcam Ltd. . The fluorescein isothiocyanate (FITC)-annexin V/propidium iodide (PI) apoptosis detection kit was purchased from Beijing 4A Biotech Co., Ltd. Matrigel was bought from BD Biosciences . The TUNEL detection Kit was purchased from Roche Ltd. . All other chemicals were of analytical grade and used without further purification.Poly (lactic-co-glycolic acid) with carboxyl groups on one end  was acquired from the Department of Pathology in the Institute of Medicinal Biotechnology at Peking Union Medical College and cultured in RPMI 1640 medium supplemented with 10% FBS at 37 °C in a humidified atmosphere containing 5% COBALB/c nude mice  were purchased from Beijing Huafukang Biotechnology Co., Ltd.  All animal experiments were approved by the Laboratory Animal Ethics Committee in the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital in Peking Union Medical College. All experimental procedures conformed to institutional guidelines and protocols for the care and use of laboratory animals.1800-PLGA2000 was synthesized as previously described  × [minor axis]2/2), and body weights were recorded from the first day of treatment until the end of the experiment. On day 21, the mice were asphyxiated to death, and the main organs and blood samples were collected. All tumor tissues were photographed for qualitative comparisons and weighed for quantitative comparisons. In addition, apoptosis in tumor tissue was detected using the terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay using a TUNEL-POD kit according to the manufacturer’s protocol. Major organs (liver and lung) were collected, fixed with 4% PFA, and examined using paraffin H&E staining to study the potential pathological changes and compared with the similarly stained sections of organs from untreated healthy mice (n = 4).The subcutaneous tumor model was established as described above. When subcutaneous tumors grew to approximately 70 mmp < 0.05, and very significant when ** p < 0.01 and *** p < 0.001. The p values were calculated according to the two-tailed Student’s t-test by SPSS 23 software .The results were all shown as mean values ± SD. The difference between two groups was considered significant when * 1800-PLGA2000 was executed according to the scheme depicted in 1800-PLGA2000 was synthesized via the amidation reaction between the carboxyl group of PLGA-COOH and the amino groups of PEI. 1H NMR spectra of PEI1800-PLGA2000, PLGA, and PEI, in which the proton signal peaks of 1.44, 3.34, and 5.13 ppm of PEI-PLGA correspond respectively to 1.54, 4.96, and 5.16 ppm in PLGA, which belong to the –CH3 of the PLGA block, –CH of the PLGA block and –CH2 of the PLGA block, respectively. In addition, the proton signal peak of 2.47 ppm of PEI-PLGA corresponds to 2.49 ppm in PEI, which belongs to the –CH2-N of PEI. The –CH in PLGA is connected to the carbonyl group, and the carbonyl group in PEI-PLGA forms an amide bond; thus, the –CH proton signal peak in PEI-PLGA was greatly shifted. All these spectroscopy results confirmed that PEI1800-PLGA2000 was successfully synthesized. In addition, as shown in −1, 1542.2 cm−1, and 1265.0 cm−1. FTIR results also showed that PLGA and PEI underwent an amide reaction to form PEI-PLGA.The synthesis of PEI5k-PLD10 was synthesized via the thiol-ene “click” reaction of the maleimide group of Mal-PEG5k-PLD10 with the sulfhydryl group of the dipeptide. Successful conjugation of Di-PEG5k-PLD10 was confirmed by the disappearance of the maleimide proton at 6.73 ppm compared to that of Mal-PEG5k-PLD10, as indicated in 5k-PLD10 showed that the average MW of Di-PEG5k-PLD10 was 14,591.75 Da, which is consistent with the theoretical MW of Di-PEG5k-PLD10 , also confirming that the target molecule was successfully synthesized.Di-PEGAs shown in The outer layer of P/AR-siRNA/DTX was coated with a layer of polypeptide-targeted anionic polymer Di-PEG-PLD via electrostatic interactions to obtain the nanocomplexes Di-PP/AR-siRNA/DTX. The particle size and zeta potential of the Di-PP/AR-siRNA/DTX nanocomplexes are shown in Under the best formulation , the particle size of Di-PP/AR-siRNA/DTX was 101.4 nm, and the zeta potential was −20.1 mV A,B. TEM As shown in To investigate if the nanocomplexes could release DTX under pH stimuli, DTX release behaviors of nanocomplexes under pH 5.5 and pH 7.4 were measured, which simulated the slightly acidic tumor cell condition and blood circulation condition, respectively. Higher cellular uptake and more specific intracellular distribution of DTX and AR-siRNA are vital for good therapeutic efficiency. The intracellular distribution of various formulations encapsulating C6 and Cy5-siRNA in LNCaP cells is shown in As shown in Androgen promotes the development of PC by binding to AR. AR-siRNA inhibits the expression of AR protein after uptake by PC cells, thereby preventing the binding of androgen and AR to inhibit the proliferation and metastasis of PC. In this experiment, the expressions of the AR protein in LNCaP cells after treatment with AR-siRNA, Di-PP, Di-PP/NC.siRNA, and Di-PP/AR-siRNA were analyzed by Western blotting. The result is shown in As shown in The antiproliferative effects of different formulations on LNCaP cells after 72 h incubation are depicted in Cell apoptosis assays were performed to determine the antitumor efficacy of co-loaded AR-siRNA and DTX nanocomplexes. The Hoechst staining assay C showed The quantification of apoptotic cells was further investigated using the Annexin V-FITC/PI double-staining assay by flow cytometry, as depicted in PSMA expression in LNCaP prostate tissues was detected using immunohistochemical staining (IHC). Positive expressions of PSMA were detected in LNCaP prostate tissue sections, as shown in p < 0.01). In addition, owing to the effective tumor targeting, mice treated with Di-PP/AR-siRNA/DTX displayed a higher rate of anti-tumor efficacy than PP/AR-siRNA/DTX (p < 0.05), as expected. Furthermore, no significant body weight loss was observed in any of the drug-loaded NP groups . On the one hand, this PEG modification improved the stability of the nanosystem during long blood circulation. On the other hand, Di-PEG-PLD, a kind of anionic polymer whose aspartic acid moiety is negatively charged at pH 7.4 but neutral at pH below 6.0, would detach from the nanosystem and hence avoid the “PEG dilemma” and give rise to rapid and triggered release of AR-siRNA and DTX . It is dThirdly, we should keep in mind at all times that another extremely important aspect for nanotherapeutics is their safety in addition to effectiveness. Compared with some delivery carriers studied for PC treatment at present, such as mesoporous silica nanoparticles , the matIn this study, we first prepared Di-PP/AR-siRNA/DTX nanocomplexes co-loaded with DTX and AR-siRNA for the targeted and coordinated treatment of PC. The nanocomplexes improved the poor solubility of chemical drugs and enhanced the stability of gene drugs in vivo. In addition, as-designed Di-PP/AR-siRNA/DTX nanocomplexes effectively and selectively carried both DTX and AR-siRNA to PC tissues and cells, which further effectively downregulated AR expression and increased the therapeutic efficacy of DTX in PC. As a result, a potential anti-CRPC effect was gained. Overall, this PSMA-targeted nanosystem may provide a promising solution for the clinically-targeted treatment of PC using chemotherapeutic drugs and siRNA drugs that silence androgen-related signaling pathways.


Augmented and virtual reality  are becoming promising tools in neurosurgery. AR and VR can reduce challenges associated with conventional approaches via the simulation and mimicry of specific environments of choice for surgeons. Awake craniotomy (AC) enables the resection of lesions from eloquent brain areas while monitoring higher cortical and subcortical functions. Evidence suggests that both surgeons and patients benefit from the various applications of AR and VR in AC. This paper investigates the application of AR and VR in AC and assesses its prospective utility in neurosurgery. A systematic review of the literature was performed using PubMed, Scopus, and Web of Science databases in accordance with the PRISMA guidelines. Our search results yielded 220 articles. A total of six articles consisting of 118 patients have been included in this review. VR was used in four papers, and the other two used AR. Tumour was the most common pathology in 108 patients, followed by vascular lesions in eight patients. VR was used for intraoperative mapping of language, vision, and social cognition, while AR was incorporated in preoperative training of white matter dissection and intraoperative visualisation and navigation. Overall, patients and surgeons were satisfied with the applications of AR and VR in their cases. AR and VR can be safely incorporated during AC to supplement, augment, or even replace conventional approaches in neurosurgery. Future investigations are required to assess the feasibility of AR and VR in various phases of AC.The online version contains supplementary material available at 10.1007/s10143-022-01929-7. Neurosurgery has always been at the forefront of incorporating technological advances to better surgical management, with the incorporation of augmented reality (AR) and virtual reality (VR) in recent years , 59, 82.Computer-generated realistic images, sounds, and other sensations in VR immerse users in artificial and synthetic environments that simulate a desired situation , 40, 65.Incorporating relevant information into the surgical field has been proposed for several years , 37. SinVR can be used in the simulation for the training of surgeons, improving understanding of complex anatomical structures, and expanding clinical assessments , 65, 82.A difference between the two modalities is that in an AR setup, computer-generated 2-D and 3-D images are superimposed into the vision of the real world , 62, wheWe conducted our systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines  to identWe considered articles eligible for our systematic review if they met the following conditions: (1) original articles, (2) published in English only, (3) used at least one aspect of AR and/or VR in AC, and (4) exclusively involving human subjects. The exclusion criterion was defined as (1) studies which investigated neurosurgical interventions other than AC, for example, minimally invasive procedures such as burr holes in deep brain stimulation , 56.Extracted data are presented in Tables Details of our search results are shown in Fig. The total sample size was 118, with the largest sample size of 55 patients reported by Roethe et al. , and then = 108, 91.53%), followed by vascular lesions  . Three studies reported preoperative symptoms in their patients, with seizure being the most common symptom recorded in 26 patients (22.03%) [The majority of pathologies operated on by AC were tumours (%) Table . The pat22.03%) , 61. Fin2.03% , 6(22.03%) , social Applications of AR and VR were specified with four papers studying VR , 18, 61 Two studies reported the mean surgery time, which were recorded as 4 h and 12 min  , and 4 hFifteen patients in three studies had previous experience using VR , 9, 18. While brain mapping during AC is mainly focused on language and motor areas , 95, VR OK, thumbs up, and clap. Bernand and colleagues concluded their study with the finding that VR could imitate complex social interactions in patients undergoing AC. The advantage of using VR to map social cognition is a fast and definite response by patients compared to other mapping approaches, such as story movies, comic strips, or interactive games, which are not compatible with a fast duration of direct electrical stimulation within a few seconds [Bernard et al.  used VR  seconds . FurtherDO-80 language denomination test, where patients are asked to name 80 objects presented to them, has been extensively used for mapping language areas , 91, andCasanova et al.  used theVR sickness is accompanied by experiences such as nausea and headache , and mayAR can be used for neurosurgical training. Surgical treatment of eloquent gliomas requires sufficient knowledge of the white matter to preserve these structures during tumour resection , 38, 80.P < 0.001). Navigation pointer was mainly used in the AR group for verifying positions during early phases of the surgery and for estimating the brain shift during advanced phases of the surgery. Head-up or head-mounted displays of AR can provide continuous integrated display, enabling pointer-less navigation. Roethe and colleagues also demonstrated that AR is most suited for deep-seated lesions (> 1 cm from the cortex), particularly during targeting small structures, defining the tumour borders, and identification of eloquent areas [Roethe et al.  investignt areas .P < 0.001), the visual accuracy of the overlay , and visual comprehensibility , in conventional navigation, due to perhaps familiarity with conventional navigation compared to AR [P = 0.060) and relevance of visualisation , between the two groups. Furthermore, important anatomic structures were blocked completely or partially and were not visible in 43.6% of cases using AR. Despite such challenges, 66.7% of surgeons found AR helpful for their surgical cases, and 76.9% of those cases were categorised as deep-seated lesions [Neurosurgeons rated higher the spatial understanding of information , head-mounted display (i.e. devices which are worn on the head or as part of a helmet), monitor- and tablet-based visualisation, and image insertion into the surgical field, have been investigated , 81, 93.AR in neurosurgery involves an overlay of the necessary information, such as CT/MRI and functional information, augmented onto the surgical field . TherebyThere are some challenges associated with AR and VR use in neurosurgery, including registration errors, depth perception errors, temporal asynchrony in visual and tactile modalities, and blocking of visual fields .The quality of AR visualisation is significantly dependent on the quality of the CT and MRI data as well as successful image fusion , 75. ResFade-in display of surgical information and pointer-free navigation may pose some challenges, such as completely or partially blocking the view of the surgical field and impairing depth assessment. One study demonstrated that most otolaryngology expert participants preferred the display of information in the periphery over AR visualisation in the focus level due to the distraction effect and visual occlusion . Other rFurthermore, mapping more complex cognitive functions, such as emotions in AC, ideally requires preoperative screening to establish the baseline characteristics of the patient as well as postoperative monitoring and rehabilitation . It has This systematic review is subject to some limitations. AR and VR in AC are relatively novel concepts reflected in the limited number of publications. Our review was limited to papers published in English, and there was heterogeneity in the articles reviewed. The patient numbers were low, and the number of participants in each study and data collection period varied widely. AR and VR technologies are not widely used in all neurosurgical settings, especially in countries with resource restraints. This was reflected in the fact that all studies included in this review were from high-income countries. Furthermore, participants in included studies were patients and surgeons, and the studies reviewed had different inclusion and exclusion criteria. No study investigated both AR and VR in the same group of participants. Studies focused on different phases of AC, namely preoperative and intraoperative, and no study was done at the postoperative phase of AC. Therefore, future studies are required to evaluate AR and VR at all phases of AC. Despite such limitations, the current review can be a useful addition to understanding AR and VR in neurosurgical procedures and prompt further research.The technologies concerning AR and VR are rapidly advancing in neurosurgery, and they can be used at different phases of AC by patients and surgeons. As the technological capability of AR and VR advances, neurosurgeons are finding more applications in training and patient interaction, within and out of the operating theatre. AR and VR have been tested against existing protocols and have been shown to generate equal or better outcomes in some studies. While the benefits of AR and VR certainly outweigh their risks, multiple factors, such as case selection, technology availability, visualisation, and technical limitations, should be considered when using AR and VR in the neurosurgical operating theatre. Results from studies included in this review can only be indicative of certain domains in AR and VR, and further technical improvements are required to eliminate existing problems with AR and VR. Development of future AR and VR environments can be customised for patients and surgeons to assess specific networks and domains that they desire to be preserved. In addition, more training is required to ensure competencies are achieved among neurosurgeons and trainees. Future prospective multi-centre studies with long-term follow-up and larger sample sizes are required to assess patient outcomes in AR and VR compared to conventional approaches.Supplementary file1 (DOCX 30 KB)Supplementary file2 (DOCX 15 KB)Supplementary file3 (DOCX 17 KB)Below is the link to the electronic supplementary material.